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The Migraine And Headache Program

In this simple program you'll learn: 5 Body balancing techniques that free your diaphragm to do its actual job of pumping fresh air into your lungs. This will ensure that your body will have enough resources to do what needs to be done including healing your headaches. Simple breathing technique that boost your oxygen level. In a few minutes of practice, your blood may carry 20% more oxygen to your brain. This can immediately reduce even the worst headaches. Other breathing exercises that spread the oxygen delivered to the brain evenly. The parts of the brain that are often highly oxygen deprived will finally receive fresh oxygen on a plate. Simple head muscle exercises that remove tension from the muscles around the head such as the the jaw, the tongue, the throat, and the eyes. These exercises can quickly relieve tension from the head and eliminate headaches in just a few seconds. New revolutionary neck exercise that removes tension from the neck. Tension in the neck muscles does not only block blood flow to the brain, but will also not support the veins in pumping the blood which is their actual function. Some people experience blast of energy rushing up to their head after doing this exercise. More here...

The Migraine And Headache Program Summary


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Vasoconstrictive effects of caffeine headache and caffeine withdrawal

The cerebral vasoconstrictive properties of caffeine have been used regularly for the treatment of painful cerebral vasodilations associated with vascular headaches. Indeed, several efficient anti-headache medications contain caffeine. The methylxanthine has also been shown to be able to relieve pain significantly and in a dose-dependent way. This anti-headache effect of caffeine is similar to that of acetaminophen (which is frequently associated with caffeine in analgesic preparations) and is also independent on the effects of caffeine on mood or on previous exposure to caffeine.55 One of the most commonly reported symptoms of caffeine withdrawal is headache that is easily relieved by caffeine consumption (for a review, see References 1 and 2). Weekend attacks in migraine patients appear to be linked to caffeine withdrawal.56 There is a strong positive correlation between caffeine consumption, fasting, and headaches before and after surgical procedures. For every increase in the...

Tensiontype headache

Studies where the most extensive study reported a significant reduction in the area under the headache curve during amitriptyline, compared with placebo, while the specific serotonin reuptake inhibitor citalopram had no significant effect.108 II The mechanism of action of amitriptyline in tension-type headache is independent of its antidepressant effect109, 110 and the effective dosage in headache is usually much lower than used in the treatment of depression, namely 10-75 mg per day. The lack of significant effect of the selective serotonin reuptake inhibitors (SSRIs)109,111 indicates that serotonergic mechanisms are not of decisive importance. The anti-depressant drug mirtazapine, which is both a serotonin and noradrenalin reuptake inhibitor, was found to be more effective in doses of 15-30 mg than placebo in one rCt,107, 112 ii whereas a lower dose of 4.5 mg alone or combined with ibuprofen (ibumetin) had no prophylactic effect.113 II A few other tricyclic antidepressants have been...

Treatment Of Cluster Headache

Attacks of cluster headache can be treated with oxygen or subcutaneous sumatriptan (6 mg).119 II For acute treatment, sumatriptan (20 mg) administered as a nasal spray was superior to placebo (57 versus 26 percent relief).120 II Intranasal zolmitriptan (10 mg) was superior to placebo (65 versus 21 percent relief) after 30 minutes.121 II The prophylactic treatment is based on verapamil in doses of 360-720 mg daily. In addition, lithium, ergota-mine, methysergide, valproate, and topiramate can be used together with verapamil, although the scientific evidence for most of these prophylactic drugs and their combinations is lacking.122 A placebo-controlled trial has

Table 81 Evaluation of the headache patient

Change in course of one's customary headache Associated features Aggravating factors Mitigating factors Factors suggesting Environmental factors secondary headache Head trauma posttrauma Infection tensity of tension headache can vary from mild to moderate in severity. Although tension headache can inhibit activities, it does not prohibit them. Tension headache is rarely aggravated by routine activities such as walking and climbing stairs. Generally, tension headache is not accompanied by nausea, vomiting, or photophobia or phonophobia. Tension headache is thought to arise from peripheral changes (i.e., myofascial pain sensitivity and increased pericranial muscle activity). It can be brought on by physical and psychological stress as well as poor posture and er-gonomic conditions. Emotional factors can contribute to the frequency and severity of headache. It is speculated that limbic system activity invoked during emotional distress might both contribute to muscle contraction and...

Table 83 Factors influencing likelihood of response to psychotherapeutic measures in patients with tension headache

Shorter duration of headache, compared with chronic headache respond favorably to occlusal adjustments and splints and therapeutic masticatory exercises. Patients with chronic daily headache are often unable to obtain much benefit from psychotherapy interventions. For such patients, the combination of psychotherapy (e.g., CBT) and the judicious use of pharmacologic interventions is likely to yield better clinical improvements than those achieved with either treatment alone (Lake 2001 Lipchik and Nash 2002).

Chronic Daily Headache Tensiontype Headache

Patients with CDHs account for about 4 to 5 of the general patient population but constitute a large percentage (80 ) of patients who are seen in specialty clinics for headache (Dodick & Saper, 2003). Chronic Daily Headache Tension-Type Headache 283 Many patients with CDH (78 ) also have chronic-transformed migraine (Dodick & Saper, 2003). Headache occurs at least 15 days per month. Headaches last for longer than 4 hours per day (Dodick & Saper, 2003). What causes a CDH The average CDH patient has a history of long-term episodic migraine, with headaches that gradually increase in frequency. There can be a family history of depression, anxiety, or alcoholism (Dodick & Saper, 2003). No matter what the cause of the CDH, the effect can be very disruptive to the patient. For patients who are overusing medications, trying to taper and stop the overuse medication can result in a withdrawal headache that will also cause pain. The vicious circle of medication use for headache and...

Other Primary Headaches

Thiere are a variety of primary headaches that are associated with a specific trigger mechanism. These headaches include Exertional headache Hypertension-related headache Thunderclap headache, which has acute onset and mimics ruptured cerebral aneurysm Primary cough headache Primary headache associated with sexual activity Primary stabbing headache Hemicrania continua, a persistent unilateral headache (ASPMN, 2009 Silberstein et al., 2005) Each of these headaches has an associated cause and treatment options that are similar to those of other headache types. No matter what the cause of the headache the patient experiences, headache pain has a significant impact on the patient's personal life and functional ability. For headaches with prophylaxis and abortive treatment option, the patient should be provided with medications that are effective to reduce the occurrence and frequency of the headache. Side effects of the headache, such as nausea and vomiting, should be treated with...

Posttraumatic Headache

Headaches can occur secondary to acute or chronic subdural hematomas. It usually presents as a severe, chronic, continuous, or intermittent headache that may last several days or weeks. Patients with subdural hematomas may feel dull, deep-seated unilateral pain often accompanied by confusion, drowsiness, and fluctuating hemiparesis. Positional worsening of the symptoms is seen with acute hematomas. Eye pain is a common feature in tento-rial hematomas, which is associated with the anatomical tent that covers the cerebellum. Diagnosis is established by CT and MRI imaging. Patients on anticoagulant therapy are at higher risk for hematomas. Either conservative treatment or surgical evacuation may be necessary.

Headaches of Brain Tumor

Headache is a common symptom in two-thirds of patients with brain tumors. They are deep seated, usually non-throbbing (occasionally throbbing) and are often described as aching and bursting. These headaches are non-specific in nature and are usually provoked by physical activity or changes in position. Diagnosis can be made based on the presence of a preexisting brain tumor and signs symptoms of increased intracranial pressure. These headaches are nearly always on the same side as the tumor and in later stages may be associated with projectile vomiting. Pain may last for hours and may recur many times during the day. These headaches are sometimes associated with vomiting, transient blindness, extremity weakness, and loss of consciousness which often show a high incidence of brain tumor.

Primary Headache Disorders

Headaches are common during childhood. In one Swedish interview study of 9000 schoolchildren,92 II 40 percent of children before age seven years reported having at least one memorable headache. In a later review by the same author, 10 percent of children reported having recurrent headaches. In another Canadian study,93 IV 85 percent of children aged five to seven years reported headaches, as did 100 percent of adolescents aged 14-16 years. Most of these pain experiences were reported as mild to moderate in intensity, of short duration, and not disruptive to daily activities. However, an increasingly recognized minority of children is reported to have daily headaches associated with significant disability. These patients present with decreased academic performance and school absenteeism, reactive anxiety, depression, disrupted family interactions, and increased healthcare costs.94 III Fortunately, most childhood headaches are benign, not associated with underlying organic pathology,...

Systematic reviews and metaanalyses in migraine

Several systematic reviews with meta-analyses of acute migraine treatment have been published 12, 37-44 . In addition, three systematic reviews of preventive migraine treatment have been published 45-47 . One should distinguish between systematic reviews in which several randomized clinical trials (RCT) of a single drug are evaluated to obtain more precise information about its merits 40, 41, 43-45, 47 and those in which several drugs or administration forms are compared in a meta-analysis 12, 37-40 . In the systematic reviews and meta-analyses of acute migraine treatment 12, 37, 38, 40-44 patients had moderate or severe headache and headache relief was defined as a decrease to none or mild 48 . Headache relief was the primary efficacy measure in most RCTs. Being pain free after 2 hours was also reported in most studies and was evaluated in some meta-analyses 12, 38, 42 . One of the systematic reviews 12, 38 also Systematic reviews of one drug for the treatment of migraine Naratriptan...

Clinical trials in tensiontype headache

Acute treatment of tension-type headache has been investigated in episodic tension-type headache, and in prophylactic treatment of chronic tension-type headache, antidepressant drugs and botulinum toxin have been investigated. Aspirin and paracetamol are the analgesics used most commonly in the treatment of acute tensiontype headache 76 . In the most recent RCT, 452 patients treated episodes of tension-type headache with aspirin (500 mg or 1000 mg), paracetamol (500 mg or 1000 mg) or placebo. Headache relief after 2 hours was 76 after aspirin 1000 mg and 71 after paracetamol 1000 mg. Both were superior to placebo despite a high placebo response of 55 . The following NSAID were superior to placebo in RCT on the treatment of acute tension-type headache ibupro-fen 77 , ketoprofen 78, 112 naproxen 79, 80 and diclofenac 81 . Caffeine has long been used as an analgesic adjuvant 76 . In a RCT the combination of aspirin and caffeine was superior to paracetamol and placebo 77 in another RCT,...

Clinical trials in cluster headache

In contrast to migraine and tension-type headache, there are very few RCT in cluster headache. This is most likely due to the fact that cluster headache is a rather infrequent disease (see above). There is one RCT demonstrating the superiority of O2 versus plain air 91 . In one RCT subcutaneous sumatriptan 6 mg was superior to placebo 92 . In another, intranasal sumatriptan 20 mg was superior to placebo 93 and intranasal zolmitriptan 5 mg and 10 mg was superior to placebo in one RCT 94 . Subcutaneous sumatriptan 6 mg is the first-line drug for cluster headache attacks but it is very expensive.

Research needed to improve the evidencebased management of migraine

Clinical experience shows that triptans are more effective in migraine than over-the-counter drugs such as aspirin 97 . In RCT, however, triptans and aspirin are comparable 98 and this was also the case in a recent systematic review including 991migraine attacks 99 . When headache was severe the results were similar 99 . It has been suggested 97 that patients treated with triptans in clinical practice may be relatively more responsive to triptans and relatively less responsive to other agents than those who participate in clinical trials. In patients recruited from general practice, however, the pain-free response 100 was similar to other studies 38 . Thus a selection bias is most likely not the reason for the discrepancy in results in clinical practice and controlled trials. The lack of superiority of triptans in controlled clinical trials has meant that the WHO has not included triptans on the list of essential drugs. subcutaneous naratriptan 10 mg 51, 101 . So inherently the...

Headache of Temporal Arteritis

This headache is caused by inflammation of the cranial arteries and is usually seen in the elderly. It presents with increasingly intense throbbing or non-throbbing headaches. There is often a superimposed sharp, stabbing pain associated with thickened and tender arteries. The pain is usually unilateral, localized to the site of the affected arteries. However, it may also present as bilateral and explosive in nature in some patients. Pain may be present throughout the day and may be more severe at night. It may last for several months, if untreated. Diagnosis is often made based on the patient's age (> 55 years of age), no previous history of symptoms, general malaise, weight loss, low-grade fever, and anemia. Erythrocyte sedimentation rate (ESR) may be elevated (> 55 mm h), and 50 of patients experience generalized aching of proximal limb muscles. A complication of temporal arteritis is blindness due to thrombosis of ophthalmic and posterior ciliary arteritis.

The Neurogenic Inflammation Theory Of Migraines

This theory suggests that migraine headaches occur as a result of an abnormal firing of meningeal nociceptors at the TGVS. Activation of trigeminal neurons releases vasoac-tive peptides including calcitonin gene-related peptide (CGRP, a vasodilator peptide), substance P, and neurokinin A (both play an important role in pain transmission as well as activation of immune responses and neurogenic inflammation) onto dural tissue where these peptides produce a local response known as neurogenic inflammation.259 These peptides induce cranial vasodilatation, especially at the dural membranes surrounding the brain (mainly a result of CGRP), thus producing the pain associated with migraine attacks. Further evidence supporting this theory as the underlying cause of migraines can be found from a recent study linking the dural mast cell degranulation to the prolonged activation of the trigeminal pain pathway and neurogenic inflammation.268 and preventive treatment of migraine and cluster...

The Vascular Theory Of Migraines

According to the vascular theory, the vasodilatation of cranial carotid arteriovenous anastomoses (sites of many 5-HT1B 1D receptors) and meningeal, dural, cerebral, or pial vessels (primary sites of 5-HT1B receptors) plays an important role in the pathogenesis of migraines and is responsible for the pain associated with migraine headaches.259,261 The fact that sumatriptan-induced cranial vasoconstriction is selectively blocked by a selective 5-HT1B antagonist, and not by a 5-Ht1D antagonist, lends further support to this vascular theory of migraines.267

Serotonin 5HT1B1D Agonists For Migraine

The possibility that acute relief from migraine might be achieved by selective activation of an atypical 5-HT receptor mediating cerebrovascular constriction was first proposed by Humphrey and colleagues toward the end of the 1970s (see Ref. 8). This concept arose from a careful appraisal of clinical and preclinical studies that suggested that (1) cranial blood vessels are in some way implicated in the manifestation of migrainous symptoms, (2) an alteration in serotonin biochemistry underlies attacks in many suffer ers, (3) many effective antimigraine drugs interact with serotonin receptors as either agonists or antagonists, and (4) serotonin and other vasoconstrictors such as norepinephrine were reported to abort induced or spontaneous migraine, whereas vasodilator agents could provoke an attack. Coupled with earlier important experiments by Saxena (9,10) showing that many antimigraine drugs selectively constrict extracranial blood vessels in vivo, these data prompted Humphrey to...


Three double-blind, randomized, placebo-controlled trials concluded that the nonprescription combination of paracetamol, aspirin, and caffeine was highly effective for the treatment of migraine headache. It also alleviated the nausea, photophobia, and functional disability associated with migraine attacks, with an excellent safety profile and tolerability.120 II A more recent double-blind, randomized, placebo-controlled study looking at headache demonstrated the combination of acetylsalicylic acid, paracetamol, and caffeine to be superior.121 II

Migraine Headache

Migraine is a very common disorder being characterized by enhanced sensitivity of the nervous system. The attack is associated with activation of the trigeminal vascular system. In 1989, a self-administered questionnaire was sent to a sample of 15,000 households (Srewart et al. 1992). A designated member of each household initially responded to the questionnaire. Each household member with severe headache was asked to respond to detailed questions about symptoms, frequency, and severity of headaches. After a single mailing, 20,468 subjects (63.4 response rate) between 12 and 80 years of age responded to the survey (Srewart et al. 1992). Migraine headache cases were identified on the basis of reported symptoms using established diagnostic criteria. An estimated 17.8 of women and 5.7 of men, i.e., about 8.7 million females and 2.6 million males, experiencing migraine found to have one or more migraine headaches per year in the United States (Srewart et al. 1992). Of these, 3.4 million...


Several pathophysiological mechanisms of migraine have been suggested genetic, neurogenic, vascular, inflammatory, or combinations of these (an update appears in Ref. 16). Very exciting data have been published in the field of genetics.17,18 In the very rare condition of familial hemiplegic migraine, mutations in the P Q calcium channel complex have been described. However, this gene has so far not been linked to migraine with and without aura.19 A genetic mechanism is undoubtedly involved as Russell et al.20 have found an increased familial risk in first-degree relatives of migraineurs. The risk appears to vary from 1.9 in migraine without aura to 3.8 in migraine with aura, and to 14 in cluster headache.20 These data indicate that the mode of inheritance is multifactorial and that the primary headache disorders have somewhat different pathophysiological mechanisms. The prevalence of tension-type headache was the same in monozygotic and dizogotic twins and it was concluded that...

Migraine Headaches

In the general population, the prevalence of migraine is 25 for women and 7.5 for men (Pringsheim, Davenport, & Dodick, 2008). In approximately 70 to 80 of migraineurs, there is a positive family history of migraine (Kolb-Lucas, 2008). The greatest incidence of migraines is between the ages of 25 and 55 years, affecting the highly productive middle-age time period. Migraine headaches are broadly classed as Migraine without aura Migraine with aura (Goadsby, 2006) An aura associated with migraine is described as a symptom or set of symptoms that occur before a migraine attack. An aura occurs in approximately 20 of all migraines (Kolb-Lucas, 2008). The aura can be experienced as flashing lights, halos, double vision, or blind spots (scotoma) that the patient sees before the headache symptoms begin. Other more neurologically related symptoms include paresthesia, hemiplegia, aphasia, or vertigo (ASPMN, 2009 Kolb-Lucas, 2008). The aura symptoms commonly develop more than 5 to 20 minutes...

Migraine With Aura

Migraine with aura has a particular set of symptoms that the patient regularly experiences before the onset of the headache. These include either visual or sensory symptoms. Migraine with aura has specific criteria, including the following Headache that has the same elements as migraine without aura No permanent effects of the headache once the postdrome occurs Menstrual migraine headaches are a women's pain syndrome that affects 50 to 60 of female migraine patients (Brandes, 2006). Menstrual migraine may occur with or without aura, but for purposes of classification, the International Headache Society describes menstrual migraine as a migraine headache without aura. In addition, the menstrual migraine occurs exclusively on day 1+ -2 of menstruation in at least 2 of 3 menstrual cycles (Silberstein et al., 2005). The cause of menstrual migraine is the variation in estrogen levels that normally occur with the menstrual cycle. Treatment options for migraine headache include the use of...

Cluster Headache

Thie cluster headache is just as it is titled headaches that occur in groups over a period of time. These headaches can occur daily for weeks or months and then a remission or attack-free period occurs. Cluster headaches are more prevalent in women than men, and the overall occurrence rate is 0.1 to 0.4 in the general population. Onset is fairly young, with the mean age being late 20s. Cluster periods can last for 2 months and range in length from 4 15 weeks. Interestingly, cluster headaches tend to occur at the same time of day and the same time of year. Criteria for cluster headaches include Headache lasting for 15 minutes to 3 hours Thie cause of cluster headaches is associated with activation of the trigeminal vascular and cranial parasympathetic pathways, with an increase in calcitonin gene-related peptide and vasoactive intestinal peptide (Goadsby, 2006). Nitroglycerin can precipitate a cluster headache, leading to the belief that increase levels of nitric oxide are also...

Tension Headache

Tension headache is the most common variety of headache (Bendtsen 2003). It usually occurs bilaterally with temporal occipitonuchal or frontal predominance. It can also diffuse and extend over the cranium. Diagnosis is made by symptoms. The pain is usually dull, aching, and may be associated with other sensations such as fullness, tightness, and pressure. Unlike the migraine headache, tension headache is not associated with throbbing pain, nausea, vomiting, photophobia, or phonophobia and usually does not interfere with day-to-day activities. Tension headache may persist for days, weeks, months, and years with mild fluctuations. It may be present throughout the day and is often associated with anxiety and depression. This headache is present when the patient awakens or may develop soon after awakening. Tension headaches occur most often in the middle-aged population and are often associated with anxiety, fatigue, and depression.

Cervical Headache

Cervical headaches are usually due to a dysfunction in the cervical spine regions as a result of trauma to the cervical areas. It is one of the more difficult types of headache to diagnose due to its etiology. It is hypothesized that changes in the blood flow to the vertebral arteries due to cervical spine dysfunction are responsible for affecting the cranial blood flow, thus causing headaches. Treatment generally involves diagnosing the underlying cervical dysfunction and restoring the normal cranial blood flow.


Children with chronic pain syndromes are often admitted for acute or abortive treatment of unbearable pain. Headaches and abdominal pain are among the most frequent reasons for pain-related admissions. Hospital admission for new-onset headache requires workup for organic disease. Occipital neuralgia with pain over the distribution of the lesser occipital nerve is common in children with achondroplasia secondary to stenosis of the foramen magnum (Kondev and Minster 2003). These acute pain episodes in the presence of chronic pain syndromes require knowledge of the chronic pain philosophies and treatment trends as well as the armamentarium to address the patient in pain extremis. One of the most frequent causes for hospital admission is headache such as in intractable migraine. Abortive migraine treatment includes oral preparations of NSAIDs, caffeine, and isometheptene. Nausea and vomiting may require administration of intravenous anti-emetics. The use of opioids or bar-titurate...

Headache assessment

The clinical interview is essential and includes both open-ended and structured questions about headache duration, location, frequency, intensity, quality, triggers (puberty, diet, worries), associated affect (How did you feel when you had your last headache ''), and accompanying symptoms. Such a symptom checklist93 IV may include feeling These symptoms may accompany the pain or may occasionally present independent of the headache. Table 44.1 Criteria for migraine without aura. B. Headache attack lasting 1-72 hours C. Headache has at least two of the accompanies headache 2. History and or physical and or neurological examinations suggest an organic disorder, but migraine attacks do not occur for the first time in close temporal relation to the disorder. Table 44.2 Tension-type headache criteria. C. Headache with at least two of the following pain characteristics A. At least ten previous headache episodes fulfilling criteria B-D. Number of days with such headache < 180 per year (<...

Primary headaches

Migraine has a uniform worldwide prevalence with a lifetime prevalence of 16 4,5 . The male female ratio varies from 1 2 to 1 3 with a more pronounced female preponderance in migraine without aura than in migraine with aura 6 . In its milder and infrequent forms, tension-type headache is a nuisance rather than a disease, but in its frequent forms, it becomes distressing and socially disturbing like other primary headaches. The prevalence of chronic tension-type headache is quite uniform, 2-3 in most studies 4, 5, 7 , and the vast majority of patients with chronic tension-type headache suffer from a daily, almost constant head-ache.The male female ratio of tension-type headache is 4 5 indicating that, unlike migraine, females are only slightly more affected 4, 5 . The prevalence of cluster headache is 1 with a male female ratio of 1 5 8 . Pain character, severity and location in primary headaches The typical migraine attack is often dominated by a severe and pulsating, unilateral pain...

Evolving Concepts of Pain

Seasonal changes could evoke particular imbalances of the humors, yielding certain disorders. For example, headache was attributed to excessive cold humors thought to result in a mucus discharge requiring application of hot effusions to the head. Interestingly, a similar process of excess liver fire was one explanation of headache in the traditional system of Chinese medicine. Consistent with both ideologies was the custom of treating pain by applying opposites, such as hot applications to the head to counterbalance and evacuate cold humors of headaches (King 1988) in the Four Humors system, while the imbalance of excess liver fire could be dispersed through needles inserted along the liver meridian and then cooled with alcohol. Used in both Eastern and Western tradition was the technique called cupping. Warm suction cups were applied to the skin that on cooling resulted in raised reddened welts thought to draw out any unbalanced humors (Rey 1955) or unblock...

Expression Analyses Rnabased Studies

Permits simultaneous assay of all of the sequences (i.e. polymorphisms) featured on the microarray. Common uses of DNA microarrays include susceptibility gene discovery and drug development. Recent success in the application of DNA microarray-based gene discovery for migraine suggest that population genetic studies of pain phenotypes are now tenable.31 In addition, the recent release of commercial DNA microarray-based pain candidate gene panels (http www.congenics.com) represents an intriguing research tool to explore inter-individual variation in pain, analgesia, and allodynia in human populations.

Alprazolam Definition

Alprazolam is a high-potency, short-acting anxiolytic benzodiazepine medication used in the treatment of anxiety, panic, and phobic disorders. It has some antispas-modic and anticonvulsant effects. It is not antidepressant. It is sometimes used in conjunction with antipsychotic medication in acute psychotic episodes. Unwanted effects include sedation, headaches, paradoxical excitement, confusion, cognitive and psychomotor impairment, and confusion in the elderly. Long-term use may induce dependence with withdrawal reactions. Recreational use and abuse can occur alprazolam is a scheduled substance.

Role Of Economics In Developing Strategies For Managing Patients With Chronic Pain

The burden of suffering pain imposes on individuals and the enormous costs, which society has to bear as a result, demonstrate that policy-makers, commissioners, and healthcare decision-makers should adopt a broad, strategic, and coherent perspective in determining issues relating to service provision and resource allocation. Fragmented, budgetary-based interventions and programs based on at best inadequate evidence do little to alleviate the problems associated with chronic pain and deprive patients of those services that would have a positive impact. Differentials between the demands placed on health services for treatments for pain relief, and other aspects of health care and the resources available to meet such needs, continue to be major headaches for those involved in policy-making, decision-making, commissioning services, and the provision and delivery of healthcare services. It has therefore been advocated that decisions relating to patient management are made with regard to...

Differential Diagnosis

Many disease processes present with pain, thus associated pain syndromes should be part of the physician's differential diagnosis (Overcash et al. 2001). Diabetic neuropathy (Tesfaye et al. 1994) is a frequently encountered pain, characterized by burning, muscle cramps, lancinating pain, metatarsalgia, hyperalgesia, allodynia, loss of proprioception, tingling, and numbness in lower extremities. Human immunodeficiency virus (HIV) patients present with pain including neuropathic, somatic, visceral, and headache symptoms. Patients suffering from autoimmune disease will often present with joint pain associated with inflammation, achiness, and stiffness. Post-surgical pain is commonly encountered and is usually somatic or visceral in nature. Infectious processes involving intra-abdominal organs are more likely to present with visceral pain while infectious processes involving the skin (e.g., herpes zoster) will present with somatic or neuropathic pain.

Precautions Toxicity and Contraindications

Major contraindications to the use of the muscarinic agonists are asthma, hyperthyroidism, coronary insufficiency, and acid-peptic disease. Their bronchoconstrictor action is liable to precipitate an asthma attack hyperthyroid patients may develop atrial fibrillation. Hypotension induced by these agents can severely reduce coronary blood flow, especially if it is already compromised. Other possible undesirable effects of the cholinergic agents are flushing, sweating, abdominal cramps, belching, a sensation of tightness in the urinary bladder, difficulty in visual accommodation, headache, and salivation.

Central excitatory systems

Several classes of antidepressant including serotonin and noradrenaline reuptake inhibitors (SSRIs, SNRIs), and tricyclic antidepressants, in particular amitriptyline, have proved effective in the treatment of certain types of neuropathic pain 63, 64 . The analgesic mechanism of action of antidepressants is not fully understood but it is thought to be independent of their antidepressant effect. Since these agents increase synaptic levels of noradrenaline and 5HT, their central analgesic action is likely to involve either presynaptic mechanisms reducing nociceptive transmission or postsynaptic mechanisms enhancing the endogenous descending inhibitory pathways. Likely targets include the activation of central inhibitory a2-adrenoreceptors and members of the inhibitory 5HT-1 receptor family as well-known analgesics such as the antihypertensive drug clonidine and the triptan family, used in the treatment of migraine, exert their analgesic effects through these receptors respectively 65,...

Toxicity Adverse Effects And Contraindications

Epi may cause restlessness, throbbing headache, tremor, and palpitations these effects rapidly subside with rest, quiet, recumbency, and reassurance. More serious reactions include cerebral hemorrhage and cardiac arrhythmias. The use of large doses or the accidental, rapid intravenous injection of Epi may result in cerebral hemorrhage from the sharp rise in blood pressure. Ventricular arrhythmias may follow the drug's administration. Epi may induce angina in patients with coronary artery disease. Use of Epi generally is contraindicated in patients receiving nonselective b receptor blocking drugs, since its unopposed actions on vascular a1 receptors may lead to severe hypertension and cerebral hemorrhage.

Disorders of unknown pathology

The most troublesome conditions that befall a pain clinic are those for which no pathology is known (Table 12.7). For the visceral disorders, no special investigations are indicated once the condition has been established and other gynecological or gastrointestinal problems have been excluded. The various headaches are diagnosed by clinical features alone, and usually do not require further investigation. The investigation of temporomandibular dysfunction is highly controversial, and beyond the scope of this chapter. Options range from nothing to MR imaging and arthroscopy. No special investigations are known to be useful for burning mouth.

Preformulation Testing Criteria

The classical preformulation studies include the physicochemical characterization of the solid and solution properties of compounds that would be useful in formulating the drug into a suitable delivery system. It is in this critical decision-making about what constitutes the suitable that many a lead compound falls through. A good pharmacological and toxicological profile alone does not suffice. The drug delivery system must be able to take the molecules to the site of action, at a cost and convenience commensurate with the treatment trends. An excellent remedy for headache that requires intravenous injection would not go past this stage on the other hand, for those drugs where there are no alternatives, such as in cancer treatment or other diseases where the patient is hospitalized and critically ill, any dosage form would be acceptable if cost and reimbursement issues do not impair the commercial projections of sales. Besides delivering the drug, the dosage form must provide a...

Herpes simplex virus type

Of virus replication, cerebral inflammation and the predilection of HSV-1 to replicate in the medial temporal lobe and orbital surface of the frontal lobes. HSV-1 encephalitis occurs at any time of the year and is characterized by the acute onset of fever, headache, irritability, lethargy, confusion, seizures, aphasia and focal deficits.1 Before acyclovir, the mortality, often due to uncal herniation, was 60-70 . Even with treatment, the mortality approaches 30 , and survivors often have permanent seizure disorders, memory loss, higher cognitive dysfunction, aphasia and focal neurological deficits.2

Smallvessel Encephalitis

This condition is usually seen in immunocompro-mised patients. Initial symptoms include headache, fever, vomiting, mental status changes, focal deficits and seizures. Disease is often subacute or chronic.38 The CSF contains a mononuclear pleocytosis and may also reveal red blood cells, mild protein elevation, and normal to low glucose. PCR may reveal VZV DNA in CSF. MRI reveals mixed ischemic or hemorrhagic infarcts, with deep-seated lesions that involve white more than gray matter. Pathological examination reveals perivenous encephalomalacia with focal hemorrhage and necrosis. Plaque-like demyelinating lesions situated at gray-white junctions are common.39 Brain vessels and parenchyma contain inclusions and viral antigen and DNA. Aggressive treatment with intravenous acyclovir, 30 mg kg three times daily, is recommended. Immunocompromised individuals who survive VZV small-vessel encephalitis may need to be maintained on oral acyclovir or famciclovir to prevent further virus...

Caffeine Withdrawal Syndrome

Condition that follows the discontinuation of caffeine intake and that is characterized by symptoms such as fatigue, headache, irritability, depressed mood. Symptoms of caffeine withdrawal syndrome are not necessarily manifested all at the same time and their intensity may

Selective Serotonin Reuptake Inhibitors

Of all three groups of antidepressants, the SSRI group (see Table 5.2) has the poorest profile for pain relief (APS, 2006). When compared with placebo, these medications did not have any significant advantage for pain relief. Given the lack of efficacy for pain relief in these medications and the profile of side effects, sexual dysfunction, anxiety, sleep disorder, and headache, the SSRIs are not medications that should be given unless there is a specific indication for use. The recommended use for this group of medications is for patients who have concurrent depression, anxiety, or insomnia (APS, 2008).

Paracetamol Weak Opioid Combinations Versus Paracetamol Alone

There are many preparations available that combine paracetamol with other analgesics. In a large, doubleblind, randomized, parallel group, placebo-controlled trial, Diener et al.102 investigated efficacy, safety, and tolerability of two tablets of the fixed combination of 250 mg acetylsalicylic acid (ASA)+200 mg para-cetamol+50mg caffeine in comparison with two tablets of 250 mg ASA+200 mg paracetamol, two tablets of 500 mg ASA, two tablets of 500 mg paracetamol, two tablets of 50 mg caffeine, and placebo in patients with episodic tension-type headache or migraine attacks. The fixed combination of ASA, paracetamol, and caffeine was statistically significantly superior to the other combina-tions.102 Many over the counter remedies contain paracetamol with a wide variety of other agents and these have not been addressed in this chapter.

Citalopram Definition

Citalopram is a selective serotonin reuptake inhibitor (SSRI). It is commonly used in the treatment of depression and some of the more severe anxiety disorders (e.g., obsessive-compulsive disorder, panic disorder, social anxiety disorder). As with other SSRIs, the most troublesome side effect of citalopram is sexual dysfunction (dysorgas-mia and erectile dysfunction) mild side effects include drowsiness, headache, and nausea. Escitalopram, the S-enantiomer of racemic citalopram, is also marketed as an antidepressant.

Natural history of nonspecific neck pain and whiplash with factors associated with chronic disability

The prognosis for whiplash is also generally favouable 12 but as already mentioned, shows great variability as to the frequency, severity and duration of disability. This variability in outcome is at least in part related to the culture of litigation and compensation 1 but this cannot explain all the differences, particularly within the same population. Two comprehensive systematic reviews 12, 13 found little consistency as to factors influencing outcome, although societal factors like litigation and compensation culture were most important 1, 24, 25 . How other societal factors influence outcome is complex and even more poorly understood 26 . Systematic reviews of prognostic factors following whiplash injury 12, 13, 17 found conflicting evidence for pre-existing physical or psychologic factors, or crash-related factors. The most consistent predictors of an unfavorable outcome from the systematic reviews and subsequent studies were severity of pain, headache and disability at...

The Response to Placebo

In his landmark paper on the power of the placebo, Beecher found that the number of patients who responded to a placebo varied between 15 and 53 (Beecher 1955). Other investigators examining such various diseases as headaches, low back pain, and angina have even reported response rates higher than 50 . The oft-cited statement that the response rate to placebo is 30 likely derives from the average of Beecher's original observations.

Substance Abuse and Dependence

Although chronic pain patients may be vulnerable to developing new substance use disorders in the course of treatment (Dersh et al. 2002, Brown et al. 1996, Dunbar and Katz 1996), investigations assessing the presence of opioid dependence in chronic pain patients have reported contradictory conclusions. Some contend that this is an extraordinarily rare event (Zenz et al. 1992) whereas other investigators have found high rates of opioid dependence in chronic pain populations (Ives et al. 2006, Wu et al. 2006). Risk factors for opioid dependence include a prior history of substance abuse prior physical sexual abuse major depression, anxiety disorders, and personality disorders (Dersh et al. 2002, Ives et al., Fishbain et al. 1998). Opioids have been a predominant focus however, several other agents used in pain treatment are likewise prone to abuse and dependence including the muscle relaxant carisoprodol ketamine ergot alkaloids and barbiturates employed in migraine treatment and...

Pharmacotherapy Of Anxiety

Superior to fluoxetine, and both duloxetine and venlafaxine also may be effective) fibromyalgia peptic ulcer and irritable bowel syndrome hot flashes of menopause chronic fatigue cataplexy tics migraine and sleep apnea. These disorders may have some psychobiological relationship to mood or anxiety disorders.

Generalized painful symptoms of depression

Several randomized controlled trials of duloxetine for depression reported significant improvements in a variety of pain symptoms, including back pain, shoulder pain, and headache.96,97,98 II The findings from these and other similar trials have been summarized and subjected to further pooled analyses.99,100,101 I Painful physical symptoms among patients with depression was the primary outcome measure for a randomized placebo-controlled trial of duloxetine.102 In this particular study, subjects who received duloxetine 60 mg daily experienced significant improvements in pain and activity-related pain interference. These clinical improvements occurred independent of changes in depressive symptoms.

Adjuvant Roles of Other Psychopharmacologic Agents Benzodiazepines

Other uses for benzodiazepines have included treatment of restless legs syndrome, tension headache, and neuropathy (Bartusch et al. 1996, Bouckoms and Litman 1985, Dellemijn and Fields 1994). Clonazepam and alprazolam might be effective in patients with lancinating neuropathic pain in which allodynia is a prominent feature (Reddy and Patt 1994, Bouckoms and Litman 1985).

Clinical Aspects Of Bacterial Meningitis

Bacterial meningitis is clinically characterized by stiff neck, headache, fever, photophobia, malaise, vomiting, alteration of consciousness, seizures, confusion, irritability, and, rarely, acute psychosis. Cerebrospinal fluid (CSF) usually reveals an elevated white blood cell count of more than 1000 white blood cells l, consisting of more than 60 polymorphonuclear leukocytes, an elevated total protein content and a decreased CSF serum glucose ratio. A CSF white blood cell count of less than 1000 cells l may be found early in the disease, in partially treated bacterial meningitis, in overwhelming bacterial meningeal infection ('apurulent bacterial meningitis') and in immunosuppressed and leukopenic patients.

Other pain conditions

Single studies have been published in musculoskeletal pain and headache (for the latter, see Chapter 34, Headache). Fifty patients with orofacial pain due to myalgia of the masticatory muscles benefited from high-dose gabapentin (mean 3400 mg day) reporting an improvement in pain and tenderness which continued after dosing had peaked.48 II Pain was reduced by 52 percent in the gabapentin group versus 19 percent in the placebo group.

Other Antiepileptic Drugs

Used in various chronic pain conditions, usually neuropathic pain and or headache. The results are mostly disappointing and the few that claim efficacy are far from convincing. Some clearly negative results from large trials involving antiepileptic drugs remain unpublished. The clinician should therefore resist the temptation to try just another drug from this class when others have failed many old and new AEDs require good understanding of their pharmacological properties and attention to detail if they are to be used safely.

Complications of neurostimulation

As with any implanted device, the potential for adverse occurrences is always present. Most of the complications of stimulation devices are related to movement of the electrodes relative to the target of stimulation. Other complications of stimulation systems include infection, hardware failure, lead fracture or disconnection, hematoma, spinal fluid leak and resulting spinal headache, discomfort over the pulse generator site, and many other rarer complications.80 V In a large retrospective trial encompassing 22 years of implanting spinal stimulators, the authors noted a 21.5 percent incidence of displaced electrodes.80 Overall, most lead migrations were easily revised with prompt resumption of effective stimulation. Infection occurred in the same series at a rate of 3.4 percent. Infections sometimes responded to antibiotics, but often required explantation of the device. Significant and recurrent lead migrations are usually treated with replacement of percutaneous systems with paddle...

Pharmacological Actions And Side Effects

An intramuscular dose of 10 mg nalbuphine is equianalgesic to 10 mg morphine, with similar onset and duration of analgesia. Nalbuphine depresses respiration as much as morphine. However, it exhibits a ceiling effect such that increases in dosage beyond 30 mg produce no further respiratory depression or analgesia. in contrast to pentazocine and butorphanol, 10 mg nal-buphine given to patients with stable coronary artery disease does not increase cardiac index, pulmonary arterial pressure, or cardiac work, and systemic blood pressure is not significantly altered these indices also are relatively stable when nalbuphine is given to patients with acute myocardial infarction. Nalbuphine produces few side effects at doses of 10 mg or less sedation, sweating, and headache are most common. At much higher doses (70 mg), psychotomimetic side effects (e.g., dysphoria, racing thoughts, and distortions of body image) can occur. Nalbuphine is metabolized in the liver and has a t 2 in plasma of 2-3...

Other Antidepressants

Mirtazapine may be helpful in mitigating symptoms associated with fibromyalgia (Samborski et al. 2004) and prophylaxis of chronic daily tension headache (Bendtsen and Jensen 2004). Researchers in two studies one involving patients with neuropathy and the other involving chronic headache patients found pain-mitigating effects with nefazodone. Patients with migraine or tension headache experienced marked reductions in the frequency, severity, and duration of recurrent headache when treated with daily nefazodone (Goodnick et al. 2000 Saper et al. 2001). Nefazodone use has been linked with hepatic dysfunction, and its use should be avoided in patients concurrently taking medications with potential hepatotoxic effects (e.g., acetaminophen). Additional clinical trials investigating the roles of these antidepressants are warranted. Trazodone appears to be minimally, but not conclusively, efficacious in pain. Although two double-blind studies demonstrated efficacy of trazodone in diabetic...

Critical evaluation of a metaanalysis of CBT

In preparing this study,3 we made a number of a priori assumptions and exclusions. First, chronic pain was accepted as a label for a heterogeneous group of pain problems in which diagnosis, site of pain, or medical findings were not apparent major sources of variance in any of the targets of treatment. This probably reflects the assumptions made in many PMPs in clinical settings. Second, we excluded studies of psychological treatments of headache because the episodic nature of chronic headache is markedly different from nonheadache. Third, we also excluded trials reporting the effectiveness of psychological treatments for children with chronic pain, see Ref. 48 I . The study was designed to answer two questions.

Primary Angiitis Of The

The most common presentation is headache with encephalopathy accompanied by multifocal signs. Neurocognitive deficits, in the form of intermittent confusion or progressive dementia with or without behavioural and psychiatric symptoms, are not uncommonly reported in histologically verified cases. Cranial neuropathies, spinal cord disease and seizures may occur. Stroke-like episodes, as mentioned before, are uncommon. However, intra-cerebral or subarachnoid haemorrhages and atypical presentations suggestive of a mass lesion or chronic meningitis have been noted.6,7,10 Patients may complain of mild malaise and low-grade fever, together with myalgias and even muscle weakness at the time of presentation. Calabrese et al analysed their population and reviewed the literature to assess cases that had received a diagnosis of PACNS with angiography alone and compared them with cases in which a histo-logical verification was made in addition to imaging studies. Their subgroup analysis showed...

MMethylDAspartate Antagonists

The side effects associated with the NMDA antagonists include sedation, dry mouth, headache, and constipation in some cases these effects may be prohibitively severe, limiting usefulness (e.g., ketamine may produce dissociation, hallucinations, frightening nightmares, and delirium) (Eide et al. 1994). Ketamine at a dosage of 50-60 mg four to six times daily (taken in juice or oral suspension) may produce pain relief without incurring these serious effects. Ketamine's hallucinogenic properties have rendered it popular with drug abusers (Dillon et al. 2003). Long-term use of ketamine is not currently advocated, partly because the long-term effects are unknown. It may result in long-term cognitive changes, hepatic dysfunction, and gastric ulcers.

Factors to Be Addressed in Psychotherapy

The experience and expression of anger may have an impact on chronic pain. Higher levels of anger (as well as depression and anxiety) are found among patients with chronic low back pain than are found among asymptomatic control subjects (Feuerstein 1986). Poorly managed anger adversely affects pain levels. In one study, patients with chronic tension headache differed from control subjects in their experience and expression of anger (Hatch et al. 1991). Headache patients were prone to hostility (i.e., feelings of resentment, suspicion, and mistrust), anger arousal (i.e., perceiving situations as annoying or frustrating and aroused to anger frequently), and anger suppression (i.e., being more likely to suppress angry feelings once aroused). However, once overtly angry, headache patients tended to expend less control over the expression of anger than control subjects. Taken together, these studies suggest that modulation of anger and hostility might be a major determinant of the...

Sumatriptan Current Views On Mechanism Of Action

Chemical structures of some 5-HT1B 1D receptor agonists under development for the acute treatment of migraine. Published affinity estimates (-log KI or -log IC50 ) at human recombinant 5-HT1 receptor subtypes are shown in the table in Figure 2. (Modified from Ref. 73.) Chemical structures of some 5-HT1B 1D receptor agonists under development for the acute treatment of migraine. Published affinity estimates (-log KI or -log IC50 ) at human recombinant 5-HT1 receptor subtypes are shown in the table in Figure 2. (Modified from Ref. 73.) Table 2 Affinities (-log Kj or -log IC50 ) at Human Recombinant 5-HT1 Receptors of Antimigraine Drugs Known to Be or Putatively Effective in the Acute Treatment of Migraine Table 2 Affinities (-log Kj or -log IC50 ) at Human Recombinant 5-HT1 Receptors of Antimigraine Drugs Known to Be or Putatively Effective in the Acute Treatment of Migraine affinity for 5-HT1A and 5-HT if receptors 23, but neither of these subtypes is thought to contribute to its...

Development Of Zolmitriptan 311C90

The research program that culminated in the development of zolmitriptan was started in April 1988, shortly after proof-of-concept studies with AH25086 and subsequently sumatriptan itself had confirmed the utility of 5-HT 1B 1D agonists in the acute treatment of migraine. The rationale for pursuing development of a second drug of this type was founded on scientific as well as commercial beliefs first, that it was indeed possible to develop a drug with an improved pharmacodynamic and pharmacokinetic profile compared to sumatriptan that might offer therapeutic advantage, and second, that as an innovative new treatment for a debilitating illness with a poorly met therapeutic need, sumatriptan would increase awareness about the utility of 5-HT1B 1D agonists and prime the market for the entry of a newer, potentially advantageous drug. Against a scientific and clinical background indicating that sumatriptan was a peripherally acting, 5-HT1B 1D receptor full agonist with poor (14 ) oral...

Support for the Serotonin 2C Receptor

The 5-HT2C receptor has been implicated as a potential therapeutic target in a wide variety of conditions including obesity, anxiety, depression, obsessive-compulsive disorder, schizophrenia, migraine, and erectile dysfunction. The 5-HT2 receptor family currently accommodates three receptor subtypes, 5-HT2A, 5-HT2B and 5-HT2C receptors, which are similar in terms of their molecular structure, pharmacology, and signal transduction pathways. Because the binding properties of 5-HT toward the The involvement of 5-HT2C receptors in psychiatric disorders has been hypothesized based largely on pharmacological and clinical studies. A number of atypical and typical antipsychotic agents, including clozapine, loxapine, and chlorpromazine, have a relatively high affinity for 5-HT2C binding sites as well as 5-HT2A. Some conventional and atypical antidepressants (e.g., tricyclics, doxepin, mianserin, and trazodone) also exhibit a similar binding affinity (Canton et al. 1990, 1996 Roth and...

Regional Anesthesia and Other Interventions

Traumatic brain injury (TBI) is another common cause of chronic pain and disability, affecting nearly 1.5 million Americans per year. The prevalence of pain following TBI varies dramatically, ranging from 18 to over 90 depending on the surveillance method, severity, and associated trauma (Cohen et al. 2004). The most common pain complaints in patients with mild TBI (Glasgow Coma Scale 13-15, loss of consciousness < 1 h) are headache (69 ), neck pain (40 ), and back pain (32 ). First-line treatments for headache prophylaxis include tricyclic antidepressants, topiramate, and gabapentin. The most frequent cause of neck pain after trauma is facet arthropathy, which may be treated with radiofrequency denervation (Lord et al. 1996, Cohen et al. 2007). Other causes of chronic neck pain after trauma include occipital neuralgia, which may respond to nerve blocks and pulsed radiofrequency, cervical discogenic pain, and myofascial pain.

Choice of311C90 as Development Candidate

Priate balance between oral bioavailability and CNS penetration. Although the selection of a compound with access to the brain clearly represented a significant risk, the ability of such a compound to inhibit cranial nociceptive processing at a point of convergence within the brainstem was highly attractive and offered a real possibility of improving on the therapeutic profile of sumatriptan. This possibility was reinforced by the subsequent publication of two studies showing that sumatriptan is completely ineffective if administered subcutaneously 20-40 min before the anticipated onset of headache in cluster and migraine-with-aura patients (63,64). This result not only implies that patients must await the development of headache before they take the drug, it calls into doubt the relevance of peripheral actions, such as cerebral vasoconstriction, in the therapeutic actions of drugs in this class. It also implies that sumatriptan may indeed act at a central site of action, accessible...

Total or individual assays

This brief review of the literature pertaining to the diagnosis of pheochromocytoma indicates that 24-h urinary measurements of individual NE, E, NM and MN might be most useful for the diagnosis of pheochromocytoma in patients with suggestive symptoms such as headache, perspiration and palpitations. Urinary DA level could also be measured if malignancy is suspected. The traditional assay of urinary VMA may not be necessary if metanephrines are quantitated. There had also been much discussion with regard to the use

Historical Human Experiments

Surprisingly, the pathogenicity of H. pylori to humans was confirmed by human experimentation. Barry Marshall, a resident doctor, was the first to do this.1 After checking the absence of H. pylori in his stomach, he swallowed H. pylori isolated from a patient. After 8 days, he felt nausea, abdominal discomfort, headache, and foul breath. On the 10th day, acute gastritis with neutrophil infiltration was observed at the pyloric mucosa. Fortunately, on the 14th day, the bacteria spontaneously disappeared, and thereafter, the histology of the stomach was greatly improved. On the other hand, Morris swallowed 3*105 H. pylori after confirming the absence of this bacterium in his stomach.22 On the third to sixth days, he felt severe abdominal pain and nausea. After 2 weeks, abdominal distention and discomfort appeared. He unfortunately failed to remove the bacteria after several trials with antibiotics. After 5 years he finally succeeded in their removal with simultaneous oral administration...

Adverse Effects And Drug Interactions

Fibric acid compounds usually are well tolerated. Side effects, most often Gl-related, may occur in 5-10 of patients but most often are not sufficient to cause drug discontinuation. Other infrequent side effects include rash, urticaria, hair loss, myalgias, fatigue, headache, impotence, and anemia. Minor increases in liver transaminases and alkaline phosphatase have been reported. Clofibrate, bezafibrate, and fenofibrate reportedly can potentiate the action of oral anticoagulants by displacing them from their binding sites on albumin thus, monitoring of the prothrombin time and reduction in anticoagulant dosage may be appropriate.

Pregnancyinduced hypertension and preeclampsia

Pregnancy-induced hypertension (PIH) and pre-eclampsia are potentially severe complications of human gestation, occurring in approximately 5 of pregnancies. The clinical symptoms are hypertension, proteinurea and edema, which may be accompanied by growth retardation of the fetus. In advanced stages of the disease the patients also show cerebral symptoms, ranging from hyper-reflexia and headaches to general fits. Further, there is increased platelet activation leading to thrombopenia. Recent theories suggest that the beginning of the disease lies in a pathologically poor invasion of fetal trophoblast cells into the uterine arteries 129 . This is followed by a decreased blood supply to the placenta which then probably causes the general vasoconstriction in order to increase the placental perfusion. During the course of the disease a dysfunction of endothelial cells develops, resulting in a disorder of platelet-vessel-wall interaction which can explain many of the typical clinical...

Adverse Reactions And Drug Interactions

The H2 receptor antagonists generally are well tolerated, with a low (< 3 ) incidence of adverse effects including diarrhea, headache, drowsiness, fatigue, muscular pain, and constipation. Less common adverse effects include those affecting the CNS (confusion, delirium, hallucinations, slurred speech, and headaches), which occur primarily with intravenous administration or in elderly subjects. Long-term use of cimetidine at high doses decreases testosterone binding to the androgen receptor and inhibits a CYP that hydroxylates estradiol. Clinically, these effects can cause galactorrhea in women and gynecomastia, reduced sperm count, and impotence in men. Several reports have associated H2 receptor antagonists with various blood dyscrasias, including thrombocytopenia. H2 receptor antagonists cross the placenta and are excreted in breast milk.

Botulinum Toxin Botox Injection

Botulinum toxin (both A and B types) has been invoked in the treatment of cervical dystonia, migraine headache, tension headache, temporomandibular joint disorders, and chronic back pain (Argoff2005). Multiple series of injections may be required to achieve maximal analgesia. Contraindications include pregnancy, concurrent aminoglycoside antibiotic use (e.g., gentamicin, tobramycin), myasthenia gravis, Eaton-Lambert syndrome, and known sensitivity to toxins. Clinical resistance brought on by development of antibodies to toxins may reduce clinical efficacy after repeated administrations.

Betaadrenoceptor blocking drugs

Other uses Beta-blockers have been used to alleviate some symptoms of anxiety, probably patients with palpitation, tremor, and tachycardia respond best (see also section 4.1.2 and section 4.9.3). Beta-blockers are also used in the prophylaxis of migraine (section Betaxolol, carteolol, levobunolol, metipranolol, and timolol are used topically in glaucoma (section 11.6).

Biology Of Malarial Infection

Malaria is typified by high spiking fevers, chills, headache, myalgias, malaise, and gastrointestinal (GI) symptoms. Each Plasmodium species causes a distinct illness (1) P. falciparum is the most dangerous. By invading erythrocytes of any age, sequestering in the vasculature, and producing vasoactive products, this species can cause an overwhelming parasitemia, hypoglycemia, and shock with multiorgan failure. Treatment delay may lead to death. If treated early, the infection usually responds within 48 hours. If treatment is inadequate, recrudescence of infection may result. (2) P. vivax infection has a low mortality rate in untreated adults and is characterized by relapses due to reactivation of latent tissue forms. (3) P. ovale causes infection with a periodicity and relapses similar to those of P. vivax but is milder. (4) P. malariae causes a generally indolent infection. Clinical attacks may occur years or decades after infection.

Toxicity And Side Effects

Doses of chloroquine used for oral therapy of the acute malarial attack may cause GI upset, headache, visual disturbances, and urticaria. Pruritus also occurs, most commonly among dark-skinned persons. Prolonged medication with suppressive doses occasionally causes side effects such as headache, blurring of vision, diplopia, confusion, convulsions, lichenoid skin eruptions, bleaching of hair, widening of the QRS interval, and T-wave abnormalities. These complications usually disappear soon after the drug is withheld. Rare instances of hemolysis and blood dyscrasias have been reported. Chloroquine may cause discoloration of nail beds and mucous membranes.

The Prostaglandins And Nonsteroidal Antiinflammatory Agents

Aspirin 5.14 is the best known of a family of drugs that are known as the non-steroidal anti-inflammatory drugs (NSAIDs). These drugs are used because of their analgesic (pain-killing), anti-inflammatory and anti-pyretic (fever reducing) properties. Aspirin has its origins in folk medicine. Chewing the bark of the willow tree (Salix europea) alleviated pain associated with rheumatism, toothache and headache. Salicin 5.15 and salicylic acid 5.16 were originally isolated from this source. They were used in the nineteenth century for the treatment of rheumatic fever and for their anti-pyretic and anti-inflammatory properties. Salicylic acid became readily available from phenol 5.17 by the Kolbe reaction. However, it produced side effects involving gastrointestinal damage. It was found that acetylation reduced these side effects and aspirin was introduced in 1899. Other salicylates derived from natural sources have useful anti-inflammatory action. Oil of wintergreen (methyl salicylate) is...

Sodium Stibogluconate

Adverse effects noted most commonly include pain at the injection site chemical pancreatitis in nearly all patients elevation of serum hepatic transaminases bone marrow suppression manifested by decreased red cell, white cell, and platelet counts in the blood muscle and joint pain weakness and malaise headache nausea and abdominal pain and rashes. Reversible polyneuropa-thy has been reported. Hemolytic anemia and renal damage are rare manifestations of toxicity, as are shock and sudden death.

Introduction And Classification

Headache is the most frequent pain disorder and has been experienced by almost everyone. Despite the widespread prevalence, the pathophysiology behind the primary headache disorders is widely unknown. Treatment strategies are still nonspecific in most cases, although acute migraine therapy with the advent of the triptans (5-HT1B 1D receptor agonists) has improved considerably in the last decade. Headache disorders are classified as primary and secondary headaches on the basis of their clinical symptoms and by means of a hierarchical and operational diagnostic system. This classification system1 is used and accepted worldwide and has improved headache research considerably. Migraine and tension-type headache (TTH) are the most prevalent primary headaches. Migraine is classified as either migraine with or without aura (Table 34.1). Tension-type headache is divided into infrequent episodic tension-type headache (ETTH) (less than one day per month), frequent tension-type headache (less...

Nonpharmacological Treatment

Physical treatment modalities, such as hot and cold packs, ultrasound and electrical stimulation, improvement of posture, relaxation, and exercise programs, have all been used. However, the majority of these treatments have not been properly evaluated, and most of the reported studies are not controlled. In one open-label study, the beneficial long-term effect of physical therapy was excellent,114 IV whereas a controlled study reported only a minor effect on headache frequency after eight weeks of standardized treatment.115,116 II A recent controlled study concluded that there was no significant effect of spinal manipulation on patients with episodic tension-type headache.98 II Likewise botulinum toxin plays no role in the treatment of tension-type headache or migraine.117,118 II

Nonopioid Analgesic Agents

Another relatively recent addition to pain therapy armamentarium is tramadol (Ultram(R) Ortho-McNeil-Janssen, Titusville, NJ), a centrally acting, synthetic, non-narcotic analgesic that has been available in the United States since 1995. Its two mechanisms of action are (1) low-affinity binding to mu opioid receptors and (2) weak inhibition of norepinephrine and serotonin reuptake. Tramadol is, therefore, a weak opioid agonist and mimics some of the properties of tricyclic antidepressants (TCAs). A recent double-blind, randomized, placebo-controlled trail in patients with painful diabetic neuropathy found that those receiving an average dose of 210 mg day of tramadol had significant pain relief with better physical and social functioning compared with patients receiving placebo (Finnerup et al. 2005). Most frequently occurring side effects were headache, constipation, nausea, and somnolence.

Differential Diagnoses

During examination of a patient with chronic facial pain, many different pain conditions, for example dental pain, must be ruled out in order for the patient to receive a diagnosis of AFP. Sometimes, diagnostic local anesthetic blocks can be useful when dental pathology is suspected to cause the facial pain. Pain originating from the maxillary sinuses often cause pain in the mid-facial region and can be ruled out by nasal endoscopy, x-ray, or computed tomography (CT) of the sinuses. Examination of the masticatory muscles and the temporomandibular joint with palpation over joint and muscles, as well as evaluation of jaw function can reveal the presence of TMD. TN can usually be distinguished from AFP by the symptomatology. Trigeminal neuralgia patients are pain-free most of the time and suffer from attacks with short-lasting, shock-like pain paroxysms (see under Trigeminal neuralgia), whereas AFP pain is constant and non-paroxysmal. Furthermore, TN, and not AFP, is characterized by the...

Petasites frigidus L Frigs

Arctic butterbur, more commonly known as petasites or Western coltsfoot, is primarily used in Western herbal medicine for the treatment of migraine headaches, allergies, and urinary incontinence. Petasites contains potentially toxic pyrollizidine alkaloids (PAs). Plants that contain PAs are prohibited from internal use in the European Union. Petasites is being cultivated to be low in or free of PAs. Petasites may also be mistakenly traded as American coltsfoot (Tussilago farfara). For the differentiation of these two species, see entry for Tussilago.

Table 86 Treatment options for back pain

The nature of the pain can simulate other disorders (e.g., trigger points in trapezius and cervical muscles can produce headache pain, and those in the paravertebral muscles can produce low back pain). Identification of trigger points is essential in diagnosing myofascial pain.

Nicotinic Acetylcholine Receptor Subtypes

When the French doctor Jean Nicot brought tobacco plant powder to cure the headache of his queen in the sixteenth century, it would have been impossible to predict that Nicot would leave his name in the history of pharmacology. The natural alkaloid in the tobacco plant was termed nicotine however, it is only centuries later, with the discovery of receptors that are specifically activated by nicotine, nicotinic acetyl-choline receptors (nAChRs), that we are beginning to

Additional Resources

Finding relief for menstrually related migraines. The Nurse Practitioner, 34(7), 7-9. Hu, X. H., Markson, L. E., Lipton, R. B., Stewart, W. F., & Berger, M. L. (1999). Burden of migraine in the United States Disability and economic costs. Archives of Internal Medicine, 59, 813-818. Martin, V. T. (2004). Menstrual migraine A review of prophylactic therapies. Current Pain and Headache Reports, 8, 229-237. Pietrobon, D. (2005). Migraine New molecular mechanisms. Neuroscientist, 11, 373-386. Stovner, L. J., Hagen, K. Jensen, R., Katsarava Z., Lipton, R., et al. (2007). The global burden of headache A documentation of headache prevalence and disability worldwide. Cephalalgia, 27, 193-210. Tepper, S. (2006). Tailoring management strategies for the patient with menstrual migraine Focus on prevention and treatment. Headache, 46(Suppl. 2), S61-S68.

Box 156 Pain treatment options dysmenorrhea [6973

If no pelvic pathology is identified, then surgical neuroablative treatment may be considered. Other potential options with varying degrees of supportive evidence include long-acting hormonal therapies and nontraditional remedies such as vitamin E and B1 supplementation, magnesium supplementation, various other dietary and herbal remedies, acupuncture, and transcutaneous electrical nerve stimulation (TENS). A Cochrane review of high-frequency TENS for the treatment of dysmenorrhea found it to be more effective than placebo in relieving menstrual-related pain. However, the TENS group did experience a higher rate of muscle vibration, skin tightness, headache, and skin irritation 70-73 .

Oxcarbazepine Definition

Oxcarbazepine is used primarily as an antiepileptic drug to control seizures in patients. However, it has gained utility in various mood disorders including anxiety, depression, bipolar disorder, as well as in the management of neuropathic pain and migraine. Oxcarbazepine is structurally similar to an older antiepileptic carbamazepine, and like carbamazepine works by reducing excessive or inappropriate excitability of nerve cells that normally occurs in conditions such as epilepsy and neuropathic pain.

Pain from Cervical Spine

Pain from cervical structures referred to the head is called cervicogenic headache. It can be experienced in the occipital, parietal, frontal, or orbital regions. The sensory axons from C1, 2, and 3 converge on dorsal horn neurons that also receive afferent supply from the trigeminal nerve. Hence pain mediated by the C1, 2, and 3 nerves is perceived in areas supplied by the trigeminal nerve. A common cause of cervicogenic headache, particularly in patients after whiplash injury, is pain from the C2-3 facet joint mediated by the third occipital nerve. The source of pain can be diagnosed using controlled diagnostic blocks. Facet intra-articular injection with steroid and more so radiofrequency neurotomy is effective in relieving pain.

Responsive Delivery Systems

The simplest responsive delivery systems use human intelligence. It is possible to argue that all drug delivery is responsive. For example, a migraine headache sufferer takes a second dose of ibuprofen because the biological process signals her that more drug is needed. In this example, the smart element (the suffering patient) is activated by pain. Diabetics adjust their insulin doses throughout the day using a variety of biological signals they might take additional insulin with a heavy meal or adjust doses for exercise diabetics can also measure glucose levels in the blood or urine in order to evaluate their need for insulin more accurately. The need for regulation of drug delivery is often so important that hospitalization is required (i.e., the intelligence of multiple humans is required to adjust the doses). Heparin is administered by computer-controlled infusion the rate of heparin delivery is regulated by modifying the rate of infusion in order to maintain a desired...

Side Effects And Toxicology

The delineation of side effects during the treatment of depressed patients is complicated because depression itself is accompanied by a variety of somatic symptoms. For example, headache, constipation, and drowsiness symptoms usually considered as side effects have been observed in more than 50 of untreated inpatients with major depression if these symptoms were each directly assessed (Nelson et al. 1984). During treatment, patients may be quick to label these somatic symptoms as side effects even if the symptoms were preexisting. Another manifestation of this issue is the rate of spontaneously reported side effects on placebo in clinical trials. One of the best examples is headache. Clinical trial data for recently marketed antidepressants indicate that the rate of headaches on placebo in depressed outpatients ranges from 17 to 24 (Physicians' Desk Reference 2002). For fluoxetine, sertraline, paroxetine, and bupropion, the rate for drug was only 1 -2 higher than that for placebo. For...

Irritable bowel syndrome

Irritable bowel syndrome (IBS) is a diagnosis of exclusion that is based on symptomatology and has been demonstrated to have associated abnormalities of motility and or sensation in different subpopulations. A frequent companion of other disorders without identifiable histo-pathology such as fibromyalgia, noncardiac chest pain, functional dyspepsia, and mixed headaches, it has similarly been associated with significant DSM-IV diagnoses such as anxiety and depression. There exist many diverse hypotheses related to the etiology of IBS. These propose that the pain may be psychosocial in origin, that the pain may be due to motility dysfunction at one or multiple sites in the gut (with dietary modifiers), or that the pain is a manifestation of visceral hyperalgesia. This visceral hyperalgesia may be due to peripheral sensitizers (e.g. mast cells) or altered central nervous system processing. Like many diagnoses of exclusion, it is likely that multiple pathophysiologies are present in...

Polycystic kidney disease

This disorder is an autosomal-dominant genetic disease that eventually leads to kidney failure. Cyst formation, rupture, infection, and secondary compression traction of neighboring structures may produce low back pain, abdominal pain, headache, chest pain, flank pain, and or leg pain.134 Renal stone formation and liver cyst formation are both common comorbidities and so reports of pain may require an assessment of those etiologies. Bajwa et al.135 have proposed a general progression from non-pharmacological methods to non-narcotic analgesics and minimally invasive procedures to progressively more invasive procedures and use of opioids. Procedures unique to polycystic kidney disease include surgical or percutaneous drainage of the cysts with marsupialization to avoid fluid reaccumulation.136

Clinical presentation of muscle spasm

Muscle spasm presents with a number of features. The patient complains of tightness and stiffness and the location of this is in a non-dermatomal pattern. It can be intermittent, eased by exercise although exacerbations after a period of exercise are common. Where it affects the shoulder girdle and neck, headache is common. Generally heat has a relaxant effect on muscles in spasm, although the duration of relief is very variable. In some situations what is apparent is a mild increase in muscle tone while at the other end of the spectrum there can be complete spasm of the muscle so that it is tightly contracted. Complete spasm of a skeletal muscle can be intermittent and unexpected with sudden onset of incapacitating spasticity.

Caffeine and cognition

Research on the effects of caffeine in the workplace is also rather sparse. However, there have been some studies, and it appears that the drug can have positive effects on mental performance. In one study, for example, managerial effectiveness was reduced when employees abstained from caf-feine.177 Another study found that moderate doses of caffeine (6 mg kg) caused people to work harder because they underestimated how hard they were working. The workers thought they were working at the same speed they worked without caffeine, but they were actually working much faster.178 It is commonly assumed that the ubiquitous office coffee pot is heavily used by workers in order to increase their levels of wakefulness, alertness, and, more generally, arousal.176 There may, however, be a number of additional perceived or actual benefits of work-related caffeine intake.92 Headaches, for example, are often reported in work settings, and one study showed that workers sometimes consume caffeine...

Other Potential Untoward Effects

Nausea and vomiting occur in some women but often disappear with time and may be minimized by taking estrogens with food or just prior to sleeping. Breast fullness and tenderness and edema may occur, which may be diminished by lowering the dose. A more serious concern is that estrogens may cause severe migraine in some women. Estrogens also may reactivate or exacerbate endometriosis.

Avoiding Illicit Use by Ongoing Assessment and Documentation

They may exaggerate or feign medical problems, for example, complain of renal colic and prick a finger to add blood to the urine specimen, so you might believe a renal stone was not visible on x-ray. Their complaints may be hard to determine objectively, such as a migraine, tic, or toothache.

Emergency Contraceptive Pills

Other relative contraindications should be considered on an individual basis, including migraine headaches, hypertension, diabetes mellitus, obstructive jaundice of pregnancy or prior oral contraceptive use, and gallbladder disease. If elective surgery is planned, many physicians discontinue oral contraceptives for several weeks to minimize the possibility of thromboembolism. These agents should be used with care in women with prior gestational diabetes or uterine fibroids low-dose pills are preferred in such cases.

Associated Conditions

There are a group of disorders that have been termed affective spectrum disorders'' which frequently coexist with one another. These include fibromyalgia, but also irritable bowel syndrome, chronic fatigue syndrome, depression and anxiety disorders, and migraine. These are all associated with psychological distress. It had been thought that depression may lead to the development of widespread pain, and although it is commonly reported in fibromyalgia (in 20-30 percent of patients) it is more likely that it in fact occurs the other way round (the pain results in depression) as the majority of patients do not suffer from any psychiatric illness and, when present, the depression can be treated without improving the pain state.

Drugdrug Interactions

Sertraline has a number of drug-drug interactions of which clinicians need to be aware. Because the drug is tightly bound to plasma proteins, caution should be employed when sertraline is used in combination with pharmaceuticals possessing similar characteristics, such as warfarin, and prothrombin time should be monitored when sertraline and warfarin are used concurrently (Zoloft 2001). The potential for serotonin syndrome may be increased when sertraline is combined with other SSRls, serotonin-norepinephrine reuptake inhibitors, or triptans used for the acute treatment of migraines. The administration of sertraline and MAOIs is contraindicated because of the significant risk of serotonin syndrome with this combination.

Adaptive And Maladaptive Aspects Of Immunologic Allyinduced Depression

Obviously, adaptive immune-mediated depression-like syndrome should be transient and restricted to the time period in which the organism is sick. Indeed, many factors have been documented to tightly regulate and limit the behavioral, neural and neuroendocrine effects of cytokines, including glucocorticoids, vasopressin, and a-melanocyte stimulating hormone (a-MSH) (Dantzer et al., 1996). Disruption of these regulatory factors might lead to impairment in shutting off the immune and neural mechanisms underlying sickness behavior, thus resulting in maladaptive depressive symptomatology. This process may underlie the Chronic Fatigue Syndrome (CFS) and the Post-Viral Fatigue Syndrome (PVFS). Both syndromes are associated with psychological changes that persist long after recuperation from viral infection (Komaroff, Fagioli, Geiger, Doolittle, Lee, Kornish, Gleit, & Guerriero, 1996). They are mainly characterized by fatigue, which reduces patients' level of everyday activity by at least...

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