The Best Ways to Treat Fibromyalgia

From Pain To Freedom

From Pain To Freedom

From Pain To Freedom is the Latest Scientific and Natural Medicine Breakthroughs to Understand and Relieve the Symptoms of Fibromyalgia!

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30 Days To Feel Better From Fibromyalgia

This Book is For You If You Can Answer Yes to Even One of the Following Questions. Have you tried many different medications to help with your pain only to find they either never worked or stopped working after a while so you keep having to switch? Have you tried many different medications to help you sleep only to still lay awake at night listening to your mind go on and on? Have you ever tried a fibromyalgia medication and then decided to end it only to find it was addictive and your doctor didn't tell you? Are you strongly against taking any or another medication for fibromyalgia because you already know it will cause more problems than it solves? Have you ever tried a fibromyalgia diet only to discover it didn't actually work for you, or you were unable to stick to it? Are you staying sane and functioning only by taking a laundry list of medications that you'd rather not take but you are afraid to stop any of them because you really need to function? Do you need to know what is really causing fibromyalgia in your body before you feel you have a hope of reversing it?

30 Days To Feel Better From Fibromyalgia Summary


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Fibromyalgia Syndrome

Fibromyalgia syndrome (FMS) affects 2 to 5 of the general patient population in the United States. However, the syndrome is more prevalent in women, 3.5 to 7 , than in men, 0.5 to 2 (Had-hazy et al., 2007). In older women, the prevalence of FMS increases to 7 (Hadhazy et al., 2007). Because of the higher prevalence in women, FMS has been relegated to the more minor conditions and minimized as a health care problem. More recent research has demonstrated some direct causal factors that point to a central nervous system neuropathic origin for the pain and have made health care providers more confident in diagnosing and treating the condition.

New Ideas in the Pathophysiology of Fibromyalgia

Originally, fibromyalgia was thought to be a condition associated with the EBV, Lyme disease, and other inflammatory diseases, but no definitive links have been established. There was also a consideration that fibromyalgia could be divided into a primary condition that occurred with no precipitating event and secondary fibromyalgia that was thought to be associated with stress, emotional distress, viral infection, or surgery (D'Arcy & McCarberg, 2005). Current research is finding evidence that the widespread pain of fibromyalgia may be a form of centrally mediated neuropathic pain. The term central amplification of the pain response is being used to account for the highly sensitized pain response that patients with fibromyalgia experience. This can be exemplified by patients who cannot tolerate the pressure, and subsequent pain, of a hug. Fibromyalgia pain is not just a series of nociceptive stimuli activating the ascending neural pain pathway it also includes the descending neural...

Treating Sleep Disorders in Patients With Fibromyalgia

Summary This journal article for health professionals reviews current knowledge about sleep disorders in patients with fibromyalgia and the treatment strategies currently used. Sleep disturbance may be central to the fibromyalgia syndrome. Many patients have difficulty in falling and staying asleep and awaken unrefreshed with intensified morning aching. Alpha-delta sleep, in which internally triggered arousal results in delta sleep deprivation, appears responsible. Moreover, such triggers may also lead to depressed and anxious mood, fatigue, morning stiffness, and musculoskeletal pain, which, in turn, contribute to the nonrestorative sleep cycle. Success in improving sleep is greatest when general approaches and specific sleep interventions are combined. Psychotherapy, behavioral therapy, and exercise may lead to better sleep habits and symptomatic relief. Tricyclic agents improve sleep and overall functioning. Benzodiazepines administered with nonsteroidal anti-inflammatory drugs may...


Those with an interest in rheumatological conditions will know all too well the significant burden of patients with pain associated with fibromyalgia. The American Pain Society suggest in their Clinical Practice Guideline of 2005 the following rules when treating fibromyalgia syndrome (FMS) pharmacologically while pointing out that treatment should also be non-pharmacological as well

Using Drugs Outside Their Licensed Indication

The medications recommended are often, but not always, licensed by the regulatory authorities for their use in these conditions. When conventional therapies fail to provide relief, less conventional treatments can be recommended, and it is much more common in these circumstances for the suggested drugs not to have a specific licence for use in that condition. When these options are suggested, it is not unusual for other practitioners to express concern about their unlicensed, off-label use. In reality, even these practitioners often prescribe medication off-label. For example, the use of a tricyclic antidepressant (TCA) for its sleep-enhancing and analgesic effect is usual in patients who receive a diagnosis of fibromyalgia, and yet no TCA has a licence for use in patients with fibromyalgia.

Transporters as Targets for Drug Discovery

Whitlock et al. describe progress in the discovery of SSRIs, noradrenaline reuptake inhibitors (NRIs), and SNRIs from 2000 to the present day. Whilst Chen et al. focus on recent developments in the search for triple SERT, NET and DAT reuptake inhibitors. The interest in these areas stems not only from the potential for improved antidepressant efficacy and side effect profiles, as has been proposed for the triple reuptake inhibitors 38 , but the recognition that by tweaking the transporter profile potential therapies for other diseases associated with neurotransmitter imbalance can be developed. For example, although duloxetine 6 (Fig. 1), a dual SNRI, was initially launched in 2004 for the treatment of major depressive disorder (MDD) 39 , since 2004 additional approvals have been granted for pain associated with diabetic neuropathy 40 and fibromyalgia 41 , for stress urinary incontinence 42 and generalised anxiety disorder 43 . NRIs have been licensed for the treatment of attention...

Functional Imaging Pain And Depression

Activation of brain structures by acute pain stimuli is different among individuals with chronic pain. In general, the primary and secondary somatosensory, anterior cin-gulate, insula, and thalamus are activated significantly less compared to normal subjects. In the aforementioned meta-analysis, the average incidence of activation of these brain regions in normal controls was 82 percent compared to 42 percent for individuals with chronic pain.14 Alternatively, among adults with chronic pain, the incidence of prefrontal cortex activation was 81 percent compared to 55 percent in normal subjects.14 The observation that activity in brain structures associated with the affective-motivational dimension of pain are accentuated in patients with chronic pain is consistent with clinical observations that these patients experience more pain-related emotions and affective distress. This postulate is also consistent with neuroimaging findings from patients with comorbid depression and chronic...

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.

Irritable bowel syndrome

This chronic disabling condition is not infrequently associated with fibromyalgia. The 5HT3 antagonist alosetron currently holds a product licence in the US for use in females with diarrhea preponderant irritable bowel syndrome. This restrictive label is because this was the group who responded to treatment in the proving studies with others having a less

NMethylDAspartate Antagonists

Research implicates the excitatory neurotransmitter glutamate in the development of central sensitization and the maintenance of chronic pain. Some evidence suggests that N-methyl-D-aspartate (NMDA) antagonists, i.e., dextromethorphan, ketamine, memantine, and amanta-dine, may have a role in mitigating chronic pain, including neuropathy, chronic phantom pain, fibromyalgia, and in cases of pain associated with spinal cord injury (Fisher et al. 2000, Sang et al. 2002). However, the analgesic effects in various trials have demonstrated inconsistent results (Eisenberg et al. 1998, Enarson et al. 1999).

Other pain conditions

Another controlled trial was conducted to assess the efficacy of gabapentin in fibromyalgia.49 II Seventy-five patients were randomized to a flexible dose of gabapentin 1200-2400 mg day, or placebo. Pain severity measured on the 11-point Brief Pain Inventory Likert subscale was greater in those on gabapentin versus those on placebo, with an adjusted treatment difference after 12 weeks of treatment (95 percent CI -1.75, -0.71). Improvement was seen in scales measuring sleep disturbance, impact of fibromyalgia, and mood, but there was no reduction in the number of tender spots. The results are similar to those obtained in a clinical trial of pregabalin in this condition.50 II

Milnacipran Analogues

Milnacipran 12, a dual SNRI, is approved for the treatment of depression 42 and is currently in phase 3 trials for the treatment of fibromyalgia 43 (Fig. 15). Interestingly, milnacipran is a polar compound with a log D of 0, and as such is different from many other centrally acting monoamine reuptake inhibitors which are far more lipophilic. The polar nature of mil-nacipran delivers an attractive PK profile in humans, with high bioavail-ability, long half-life and renal elimination of unchanged drug as the primary route of clearance 44 . Despite its polar nature, milnacipran is still believed to exert its pharmacology via central inhibition of serotonin and noradrenaline reuptake. The lack of interaction of milnacipran with P450 enzymes as either substrate or inhibitor reduces the potential for drug-drug interactions, which are highly prevalent for many other marketed monoamine reuptake inhibitors. This attractive physicochemical and PK profile, coupled with clinical efficacy, has...

Prevalence in inpatients

In Israel, the prevalence of FMS in patients hospitalized on internal medicine wards was reported to be 15 26 . We found no data on the prevalence of FMS in pain clinics. The percentage of inpatients with chronic widespread pain in German pain clinics was reported to be 25-30 27 (Schiltenwolf, personal communication, 2008). The percentage of inpatients with the primary diagnosis of FMS in a German interdisciplinary secondary care pain clinic was 3.6 (Gockel, personal communication, 2008). The lack of data on FMS in German pain clinics can be explained by the skepticism of most pain therapists about the use of this diagnostic category. Most patients with FMS are coded as somatoform pain disorder (Schiltenwolf, personal communication, 2008). The fact that the diagnosis of a somatoform pain disorder and inpatient multidiscipli-nary treatment leads to higher remuneration than the diagnosis of FMS within the German diagnosis-related system might also explain the coding preferences of...

Duloxetine and Propanamine Analogues

Duloxetine 11 (DLX), a dual SNRI, is approved for the treatment of depression 49 , pain associated with diabetic neuropathy 50 , fibromyalgia 51 and stress urinary incontinence 52 . Gallagher et al. at Eli Lilly have recently described the medicinal chemistry programme which led to the discovery of duloxetine 53 . Phenyl-naphthalene lead 58 showed encouraging levels of dual SNRI activity (Fig. 21, Table 8) however, substitution on the phenyl ring generally led to an erosion of NA reuptake activity. Bio-isosteric replacements of the phenyl group were then sought, and the 2-thienyl 59 was identified as a lead compound. The separate enantiomers 60 and 11 showed subtly different pharmacology, and (S) enantiomer 11 (duloxetine) was progressed on the basis of increased 5-HT reuptake potency. Rat microdialysis experiments were then carried out with 11 to determine the increase in synaptic concentrations of 5-HT and NA. Following po dosing at 10 mg kg, increases over basal levels of 5-HT and...

Physical and occupational factors

A British population-based prospective survey found that pushing pulling heavy weights, repetitive wrist movements, kneeling and local pain complaints at baseline were associated with new-onset chronic widespread pain. However, the strongest predictor was a high score on the Illness Behavior Scale 44 . Harkness et al. 45 demonstrated in a prospective British study that those who reported low job satisfaction, low social support, and monotonous work had an increased risk of new-onset widespread pain.

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...

Risk factors for chronicity

In a British prospective, population-based study, persistent chronic widespread pain was strongly associated with baseline test scores for high psychologic distress and fatigue. In addition, these subjects were more likely to display a pattern of illness behavior characterized by frequent visits to medical practitioners for symptoms disrupting daily activities 46 .

MMethylDAspartate Antagonists

Although the mechanisms are complex and have yet to be fully elucidated, research implicates the excitatory neurotransmitter glutamate in the development and maintenance of chronic pain. Some evidence suggests that NMDA antagonists (i.e., dextromethorphan, ketamine, memantine, and amantadine) may therefore have a role in mitigating chronic pain, including neuropathy, chronic phantom pain, and fibromyalgia, and pain associated with spinal cord injury (Fisher et al. 2000 Sang et al. 2002). However, the analgesic effects in various trials have been inconsistent (Eisenberg et al. 1998 Enarson et al. 1999).

Human clinical pain

Fibromyalgia Several reports suggest that IV lidocaine can reduce the pain associated with fibromyalgia, a condition remarkable for its resistance to other forms of analgesic medication. These reports are of particular note, not only because they testify to an analgesic effect with IV lidocaine but also because of the duration of pain relief produced by infusion. In one study, daily lidocaine infusion produced pain relief that persisted until day 30 after treatment commenced, while in the other, over 40 of patients achieved between 13 and 18 weeks of pain relief after treatment.

Other Psychiatric Disorders and the Immune Response

Some evidence suggests that other stress-related neuropsychiatric conditions may be associated with immune activation, although these conditions are less well characterized than major depression. These disorders include posttraumatic stress disorder (PTSD), chronic fatigue syndrome (CFS), seasonal affective disorder (SAD), and fibromyalgia. Patients with combat-related PTSD have been reported to demonstrate increased plasma concentrations of IL-1 and increased CSF concentrations of IL-6 (Baker et al. 2001 Spivak et al. 1997). PTSD following civilian disasters appears to be associated with elevated plasma concentrations of IL-6 and its soluble receptor (Maes et al. 1999c). Although not found consistently (Maes et al. 1999c), both severity of symptoms and duration of illness have been reported to correlate positively with indices of immune activation in PTSD (Miller et al. 2001 Spivak et al. 1997). A growing body of literature suggests that patients exposed to early life trauma may be...

Bladder painbladder pain syndrome

There may be genetic influences on the development of BPS IC as first-degree relatives of sufferers have a higher prevalence than the general population. It has been demonstrated that there is a particularly high proportion in the American Indians of Cherokee descent, approximately 17 14 . BPS IC is also reported to be associated with inflammatory bowel disease, systemic lupus erythematosus, irritable bowel syndrome and fibromyalgia 15 .

Nonpharmacologic Options

Treating fibromyalgia requires a combination of therapeutic options in addition to pharmacologic prescriptions. It is not a condition than lends itself to monotherapy. Using a combination of medications with integrative medicine techniques typically yields the best outcomes and provides the biggest benefit to the patient. The APS Fibromyalgia Guidelines (2005) recommend the addition of one or more of the following therapies

Nonpharmacological Therapy

Fibromyalgia is a major chronic pain syndrome which can lead to a significant decrease in overall function, long-term disability, and a decrease in the quality of life. Its pathophysiology is complex and is still under investigation. Recent research has shown the probability of central sensitization and exaggeration of wind up as part of pain processing in these patients. The definitive diagnosis of fibromyalgia is not clear-cut, because of the multiple overlapping pain syndromes which can be part of the differential diagnosis. Also, its nonspecific nature can lead to underdiagnosis. Thus, a multidisciplinary treatment approach appears to be the most appropriate and effective method.

Musculoskeletal Pain Myofascial Disorders

This is a common presentation of pain in the orofacial region. Patients may present with diffuse aching pain affecting several muscle groups. Trigger points or tender points may be elicited and pain may radiate (e.g., masseter to the ear, temporalis to the frontal area). This type of pain presentation may be seen in patients with fibromyalgia and other systemic illnesses such as lupus erythematosus.

Interstitial cystitis

The frequent association of IC with other chronic diseases and pain syndromes such as inflammatory bowel disease, systemic lupus erythematosus, irritable bowel syndrome, sensitive skin, fibromyalgia, and allergies55 speaks to the fact there may be multiple different pathophysiologies grouped together under one diagnosis. Recent studies have demonstrated some histopathological differences in bladder biopsies from patients with IC versus normal controls with increased expression of substance P-con-taining nerve fibers and substance P receptor-encoding mRNA,5657 increased nerve growth factor content,58 and altered mast cell activity.59 The meaning of these findings is still to be determined.

Lidocaine intravenous

The intravenous (IV) infusion of lidocaine can produce pain relief that persists for much longer than the infusion period or the useful plasma half-life of the drug. Therefore, an infusion given over 30 h, for example, can be rewarded with pain relief that persists for weeks, and even months. The advantage of this form of therapy is that during the period of pain relief, the patient can reduce and even stop concomitant medication with all the advantages of the decrease in drug-related side effects that this can produce. The response to IV lidocaine is not universal. From experience it would seem that about half the fibromyalgia patients who receive IV lidocaine gain relief, although the period of relief can vary from weeks to months. No matter how impressive the relief is, one can expect with certainty that at some stage it will ware off and this can happen suddenly. The infusion can then be repeated as tachyphylaxis does not seem to occur.

Principles of treatment

Fibromyalgia is particularly noted for the lethargy, sleep disturbance, and mood change that accompany pain. While medication can be provided for pain relief, the potential for worsening the accompanying functional impairment that comes with the use of many types of medication may result in those analgesics exacerbating, rather than relieving the patient's overall condition. Therefore, any use of pain-relieving medication should be accompanied by an assessment not only of the pain relief that it produces, but also its overall effect on quality of life. In many cases a modest reduction in pain with no side effects is of more value than substantial pain relief accompanied by undue sedation, weight gain, or cognitive impairment, for example. Further, since patients with fibromyalgia have a variety of other symptoms apart from pain, they may need to take other non-analgesics for these symptoms. Therefore there is a danger that they consume ever increasing numbers of tablets with the...

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.

Neuroendocrine Alterations

Another hypothesis involves the role of proin-flammatory cytokines which could induce hyperalgesia in the central nervous system (CNS). Release of these cytokines can be triggered by chronic stress. They are known to directly contribute to peripheral and central neuropathic pain as well as depression and can lead to exaggerated pain states similar to those seen in FMS.47 A recent study in 40 patients with chronic widespread pain, including 26 with FMS and 40 age- and sex-matched healthy controls, found lower relative gene expression for the anti-inflammatory cytokines interleukin-4 and interleukin-10.48

Clinical Presentation

The primary presenting symptoms are diffuse persistent or intermittent MSP involving the extremities, back, and neck that may not manifest concurrently and are present for at least three months duration. Earlier criteria proposed for the diagnosis of JFS emphasized the combined importance of symptoms and tender points.23 III Subsequent revised criteria from multicenter adult study, the American College of Rheumatology (ACR) criteria, showed that concurrent presence of widespread pain and tenderness on palpation in at least 11 of 18 tender point sites have better sensitivity (88 percent) and specificity (81 percent).24 IV However, the proper diagnostic criteria of tender points are subject to assessors' training and performance of a thorough physical examination.23 III The pain is often associated with many subjective symptoms some investigators have noted overlapping complaints of fatigue ranging from 20 to 100 percent.25 V , 26 V A recent study suggested that a combination of a high...

Irritable bowel syndrome functional bowel disorders

With depression and or an anxiety disorder 23, 24 . IBS symptomatology is present in many cultures, with similar prevalences noted in Britain, China, India, Japan, New Zealand, the United States and South America. Other disorders without identifiable histopathology such as fibromyalgia and mixed headaches are common co-morbidities 24 .

Definition and classification

According to the criteria of the American College of Rheumatology (ACR), fibromyalgia syndrome is defined as chronic (> 3 months) widespread pain (CWP) (including pain on both sides of the body, above and below the waist, and axial pain) and tenderness on manual palpation in at least 11 out of 18 defined tender points 4 . Chronic widespread pain and tender points do not capture the essence of all FMS-associated symptoms 5, 6 . Other key symptoms of FMS are fatigue and nonrestorative sleep. Most patients complain of additional somatic and psychological symptoms 7, 8 . The term fibromyalgia syndrome is preferable to fibromyalgia because the definition of FMS according to the ACR-criteria is based on a combination of symptoms (CWP) and clinical findings (tenderness). Because no consistent anatomic or specific pathophysiological mechanisms have yet been identified 9 , FMS can be classified as a functional somatic syndrome 10, 11 . Fibromyalgia is listed in the International...

Painful bladder syndrome interstitial cystitis

Painful bladder syndrome (PBS alternatively known as bladder pain syndrome) is a descriptive diagnosis that has been recently advocated for use on an international level as descriptive of a complex of urologic complaints including pain 59 . Thought to be an early form of the disorder interstitial cystitis (IC), there is an expectation that a majority of patients with PBS might have a common etiology. Notably, IC has no agreed etiology, pathophysiology or treatment and nor does the less defined PBS. The prevalence of IC is estimated to be 2 in 10,000 with a female to male ratio of 10 1. Patients with IC are 10-12 times more likely to report childhood bladder problems than the general population 60 . IC is frequently associated with other chronic disorders such as inflammatory bowel disease, systemic lupus erythematosus, irritable bowel syndrome, sensitive skin, fibromyalgia and allergies 61 .

Clinical use of 5HT3 antagonists

Fibromyalgia It is suggested that ondansetron be used for neuropathic pain and fibromyalgia treatment and granisetron for tender point, intra-articular, and nerve block injections. There is no logic to why a differing 5HT3 antagonist is used in these circumstances and why other 5HT3 antagonists are not used. It merely reflects habit.

Topical Tricyclic Antidepressants

Few classes of drugs are more extensively used in the management of chronic pain conditions than the tricyclic antidepressants (TCAs). Substantial and convincing evidence supports their use in a variety of pain conditions including neuropathic pain and the pain associated with fibromyalgia. Their use is so common that it is now normal for them to be initiated by General Practitioners. The pain relief that may be apparent is independent of their antidepressant effects but any mood improvement that may occur is often welcome. In addition to pain reduction and mood improvement, muscle relaxation and normalization of sleep pattern may also occur. All oral TCA used for a pain indication is off label.

Noradrenaline Reuptake Inhibitors

Selective inhibition of noradrenaline reuptake has been shown to be an attractive approach for the treatment of a number of diseases. For example, reboxetine 14 (Sect. 4.1.1) is used clinically for the treatment of depression and atomoxetine 13 (Sect. 4.2.1) is a new therapy for the treatment of ADHD (Fig. 30). Furthermore, NRIs are under investigation as potential therapies for chronic pain, urinary incontinence, fibromyalgia and a variety of other indications 64,65 . A number of reviews have been published that summarize discoveries of NRIs 66-69 . The (+) enantiomer of reboxetine is being developed by Pfizer as a potential oral treatment of neuropathic pain and fibromyalgia 77 . Esreboxetine (+)-(S,S)-reboxetine SS-RBX 93 is more potent than reboxetine racemate with respect to inhibiting the uptake of NA and much weaker at inhibiting uptake of 5-HT the combination of these two pharmacologies makes esreboxetine highly selective for NRI over SRI 76 (Table 14). In addition,...

Key Learning Points

Fibromyalgia is characterized by chronic widespread pain, whereas pain in myofascial pain is localized. Fibromyalgia is a syndrome associated with a wide range of symptoms and other conditions, one of which is myofascial pain Fibromyalgia arises at least in part due to an alteration in central pain processing. There are (at least) three different subgroups of fibromyalgia patients who respond differently to management strategies.

Adjunctive Interventions

This technique is useful in tension headache, temporomandibular joint disorders, fibromyalgia, and other myofascial pain disorders. Thermal biofeedback monitors skin temperature to give the patient an indicator of the degree of peripheral vasodilation. The cooler the skin, the greater the vascular constriction this reflects the amount of prevailing sympathetic activity. By increasing the skin temperature, one is able to suppress the extent of sympathetic activity. This approach has been used in the treatment of migraine and sympathetically maintained pain. Electroencephalography has also been linked with biofeedback. Brain electrical activity is fed back to the patient and is subject to modification by the patient. The goal is to achieve states of alpha rhythm brain activity that reflect a state of relaxation. Customarily, electroencephalographic biofeedback is quite cumbersome and is not regularly used in pain treatment settings. Relaxation and imagery (R& I) has been employed in...


Literature searches on therapeutic options for treating mechanical neck pain were carried out using the following databases Chirolars (now called Mantis), Bioethicsline, CINAHL, Current Contents, and Medline, with data being used to prepare and update an article in Clinical Evidence 2 . I will summarize the evidence on treatment modalities currently in use, with an indication of questions which still need to be answered. Studies relating to specific conditions like fibromyalgia and disk prolapse will not be discussed.

Muscle Relaxants

Muscle relaxants are a good addition to a pain regimen for low back pain, where muscle spasms occur regularly. They are also useful for conditions such as fibromyalgia, where cyclobenzaprine is considered a first-line option (APS, 2005 D'Arcy & McCarberg, 2005). The group of medications generically called skeletal muscle relaxants (see Table 5.5) consists of several different groups of medications benzodiazepines, sedatives, antihistamines, and other centrally acting medications (APS, 2008).


Currently just three of the AEDs have a specific pain indication. Carbamazepine is indicated for trigeminal neuralgia with gabapentin having a US licence for postherpetic neuralgia (neuropathic pain in the UK) and pregabalin for fibromyalgia, postherpetic neuralgia and painful diabetic neuropathy (peripheral neuropathic pain in the UK). The gulf between what is officially licensed and what can be effective is as wide among the AEDs as any other drug group. The possession of a marketing authorization or specific indication does not suggest that a particular drug is superior than any other drug which may be used off-label. It merely suggests that evidence of efficacy has been sought and presented in an acceptable way to the licensing authorities. From a purely scientific perspective, we lack the comparative studies that would advise us as to the best drug choices in an individual drug class.


Several meta-analyses and evidence-based reviews suggest that antidepressants are useful in mitigating pain associated with neuropathy (Collins et al. 2000, Saarto and Wiffen 2007), headache (Tomkins et al. 2001), fibromyalgia (Arnold et al. 2000, O'Malley et al. 2000), and irritable bowel syndrome (Jackson et al. 2000, Lesbros-Pantoflickova et al. 2004). Although antidepressants are advocated for use in other chronic pain syndromes, e.g., rheumatologic pain conditions, chronic pelvic pain, interstitial cystitis, and oro-facial pain (Kelada and Jones 2007, Onghena and Van Houdenhove 1992, Reiter 1998), these assertions are not often based on a solid foundation of empirical work. In fact, in some of these conditions, e.g., chronic pelvic pain and interstitial cystitis, there are few randomized controlled trials with small sample sizes upon which such recommendations are based (Onghena and Van Houdenhove 1992, Sharav et al. 1987, Stones et al. 2007, Van Ophoven et al. 2004).


The first RCT on the effect of pregabalin in chronic pain was published in 2003, and in the following four years results from 11 such trials were published. Eight reports dealt with diabetic polyneuropathy and or PHN, two with central pain, and one fibromyalgia. In addition, reports on the usefulness of pregabalin as a perioperative adjunct medication to reduce postoperative pain have started to emerge. In 7 out of 11 chronic pain studies an enriched enrollment method was used, in the sense that the patients who previously had not responded to a moderate dose of gabapentin (1200 mg day) were excluded. Two studies specifically stated that all patients with previous


A fatigue score 6 on a 11-point visual analog scale (VAS). The use of standardized somatic symptom scales and questionnaires such as the Patient Health Questionnaire PHQ 59 can be considered in primary care. Restrictions of daily life associated with FMS symptoms can be assessed by the Brief Pain Inventory 60 or the Fibromyalgia Impact Questionnaire 61 .


Selective monoamine reuptake inhibitors (SSRIs and NRIs) have had a significant impact on the treatment of several serious diseases, including depression, ADHD, neuropathic pain and fibromyalgia. The discovery and launch of dual pharmacology SNRIs such as duloxetine has further expanded the treatment options for these diseases. This review has highlighted the discovery of many new compounds which combine selective inhibition of SERT and or NET activity with a large degree of both structural and physicochem-ical diversity. The coming years will determine whether any of these recently discovered compounds will advance to clinical development and ultimately to regulatory approval as new medicines.

Assessment Tools

There are two common assessment tools that are used with patients with fibromyalgia. The Fibromyalgia Impact Questionnaire (FIQ) assesses health status in patients with fibromyalgia. The format is a short 10-item survey that asks questions about physical functioning, work status, depression, anxiety, sleep, pain, stiffness, and fatigue. To score the FIQ, each of the 10 questions has a maximum value of 10. The values of the 10 questions are combined to yield an overall score. The higher the score, the greater the impact of FMS on the patient.

Treatment Options

There are a wide variety of medications being used to treat the pain and other elements of FMS. The three medications that have approval from the U.S. Food and Drug Administration for treating fibromyalgia pain are Other medications used to treat fibromyalgia that have evidence of efficacy are as follows

HT3 antagonists

It has earlier been described how 5HT3 antagonists can be used to treat fibromyalgia, irritable bowel syndrome, and neuropathic pain. It is now known that they can also be used by the intra-articular route and that the pain relief that is produced is at par with that produced by corticosteroid injection. When given into a joint, there is a clinical impression that they cause a flare of pain that can last for several days, before pain relief is produced. The benefit of use of this class of medication is that it is devoid of the risks associated with repeated corticosteroid injection.


The etiology of fibromyalgia is unclear, but evidence suggests that it is a heritable disorder. The etiology of fibromyalgia is now thought to be due to a combination of several factors associated with the presence of both chronic pain and affective disorders, similar to those postulated in irritable bowel syndrome, chronic fatigue syndrome, major depressive disorder, temperomandibular joint disorder, and tension and migraine headaches. The factors include genetic factors, aberrant pain processing in the central nervous system, abnormalities in the neuroendocrine system, and specific triggers in the environment. Genetic relationships have been found between fibromyalgia and several genes, including genes encoding proteins in neurotransmitter signaling, catechol-O-methyltransferase, and dopaminergic signaling. Patients with fibromyalgia have enhanced sensitivity to several stimuli including heat, pressure, and sound. Patients with fibromyalgia have been noted to have lower pain...

Signs and Symptoms

Other factors associated with fibromyalgia include fatigue and sleep disturbances such as reduction in delta sleep and nocturnal myoclonus. Fatigue has been seen in about 90 of cases studied. Cognitive deficits in memory and vocabulary are also seen in patients with fibromyalgia.


The foremost complaint of patients with fibromyalgia is pain. The American College of Rheumatology states that fibromyalgia is diagnosed when there is widespread pain involving three out of four quadrants of the body for at least 3 months in duration. The criteria for the diagnosis of fibromyalgia includes widespread pain encompassing the axial system and involving both sides of the body above and below the waist, and also includes the presence of tender points. Axial skeletal pain must be also be present, such as pain involving cervical or thoracic spine, anterior chest, and lower back. Despite these guidelines, the diagnosis of fibromyalgia still can be challenging, since there are many other conditions that have overlapping signs and symptoms. These conditions include It is important to remember that detailed medical evaluation and diagnosis by exclusion are important in order to distinguish fibromyalgia from these other conditions.


Treatment of fibromyalgia should be multimodal and include control of Table 25.1 Effectiveness of pharmacological agents in the treatment of fibromyalgia Table 25.1 Effectiveness of pharmacological agents in the treatment of fibromyalgia work, including housework, because of fibromyalgia Question 4. When you worked, how much did pain or other symptoms of your fibromyalgia interfere with your ability to do your work, including housework


Serotonin and norepinephrine reuptake inhibitors (such as duloxetine) and tricyclic antidepressants are commonly used to treat fibromyalgia. Cyclobenzaprine has been shown to be effective as a muscle relaxant in treating some of the symptoms of fibromyalgia, but it did not reduce the tender points or fatigue associated with the disease. Another potential useful agent is pregabalin - an antiepileptic drug which binds to the alpha-2 delta subunit of the voltage-gated calcium channels. It is approved by the Food and Drug Administration (FDA) for the treatment of fibromyalgia. Of the selective serotonin reuptake inhibitors, fluoxetine has shown reduction in symptoms. Tramadol, a weak opioid, also has been used with some success in patients with fibromyalgia. However, the use of strong opioids in fibromyalgia has yet to be evaluated. As described above, there are several pharmacological treatments that have been employed over the years for the treatment of fibromyalgia all showing varying...


Both animal and human studies have shown that carnitine can reduce neuropathic pain and in particular that associated with cancer chemotherapy. It can also have a useful effect in patient with fibromyalgia. In the UK carnitine is sold in health food shops and has a suggested indication of weight loss (it has an effect on fat metabolism) and depression. Many patients like the concept of using something that is freely available over the counter and perceive that type of availability as indicating safety with use. We know that carnitine has an effect of glutamate receptors and this is probably what endows it with pain-relieving properties. Side effects with use are few and any antidepressant effect in a patient group in whom depression is a frequent accompaniment is welcome. A number of the drugs used conventionally in fibromyalgia treatment, such as the tricyclic antidepressants, and certain anti-epileptics are known to cause weight gain, so the propensity of carnitine to achieve weight...


Sleep disturbance is a major problem in patients with fibromyalgia. Tricyclics are often initiated as much to regularize sleep patterns as to reduce pain. Clonazepam, a long-acting benzodiazepine, can be a useful alternative to a tricyclic. It combines analgesic, antispasmodic, and anxiolytic properties with its hypnotic effects. Morning hangover is a real possibility after dosing the previous evening and may require careful manipulation of dose to minimize this troublesome side effect. That said, clonazepam is a useful drug particularly as its major effects mirror what is problematical in the fibromyalgia patient.


While the use of oral tricyclic antidepressants in patients with fibromyal-gia is widespread, use of the topical formulations of these drugs, of which doxepin is the most readily available, is less common. Since the tricyclics may achieve pain relief by both peripheral and central modes of action, the topical, peripheral use of these drugs can achieve pain relief without the side effects associated with the systemic use of these drugs. Clearly fibromyalgia is a condition where pain is widespread and the extensive use of a topical tricyclic would be associated with significant systemic uptake and side effects, patients with fibromyalgia often complain of pain that is worse in certain locations and these can be therapeutically targeted with a topical tricyclic antidepressant such as doxepin.

Pain Syndromes

Fluoxetine has shown efficacy in reducing pain associated with diabetic neuropathy (Max et al. 1992). Fluoxetine (20 mg day) improved scores on measures of pain and discomfort in subjects with fibromyalgia, compared with subjects on placebo (Arnold et al. 2002 Goldenberg et al. 1996). The effect of fluoxetine combined with amitriptyline was superior to the effect of either agent used alone. Fluoxetine reduced the number of attacks in patients with migraine headaches (Saper et al. 1994). More recent work has demonstrated that antidepressants that also affect the NE system (i.e., serotonin-norepinephrine reuptake inhibitors SNRIs ) are more effective than the SSRIs in treating neuropathic pain (Mochizucki 2004 L. H. Pedersen et al. 2005). In fact, the SNRI duloxetine has received FDA approval for the treatment of neuropathic pain.

Muscle Anomalies

The generalized muscle pain frequently appears to be exhibited following suffering of localized muscle pain,29 often due to injury, such as whiplash30 or low back pain.31 Although no obvious muscle or tissue damage is present in FMS patients, some changes within the muscle have been reported. The microcirculation of muscles appears to be altered resulting in reduced muscle tissue oxyge-nation.32,33 This is not specific to FMS, but may be important for onset of pain and hypersensitivity in chronic pain conditions. This can cause other muscle changes which have also been observed in fibromyalgia patients, including red ragged and moth-eaten'' fibers, possibly due to distribution and proliferation of mitochondria and various metabolic effects. Hypoxia of muscle tissue may lead to the release of pain substances including serotonin, bradykinin, substance P, and histamine, which sensitize nociceptive fibers, and is exacerbated during contraction of the muscle.

Other Therapies

A range of dietary interventions has been studied in fibromyalgia, however, no one treatment has more than one study. A randomized controlled trial using Chlorella pyrenoidosa supplements showed improvements in the treated group for pain and function, however, the patients also continued their usual treatment.83 Vegan and vegetarian diets have also been reported to show some nonsignificant improvements, as have ascorbigen (with broccoli power) supplements.84,85,86 Complementary


Long-term cohort studies in the Americas and Europe found no significant change in FMS prognosis over a sixto eight-year period.6,125 Severity of pain, fatigue, disability, and quality of life remains unchanged. In America, the annual healthcare cost of FMS in 1996 was 2274 per patient. Confronted by such worrying statistics, the Chief Medical Officer in the UK wrote to all the doctors in the UK emphasizing the healthcare burden of chronic widespread pain, urging that more research is essential to address the problem and improve outcome.


Tropisetron belongs to the 5HT3 antagonist group of drugs. This group has been marketed for its antiemetic effect which is most well established in the fields of postoperative nausea and vomiting and in chemotherapy-induced nausea. More recently it has been shown that 5HT3 antagonists, when given systemically, can also have an analgesic effect on the pain associated with fibromyalgia and irritable bowel syndrome and even in patients with neuropathic pain. This effect is produced by their specific action on the NKl-expressing neurones in the superficial laminae of the dorsal horn. These NKl-expressing neurones contain receptors for substance P. The potential advantage of such use of tropisetron would be that steroid-related side effects could be avoided. There are, however, a number of unanswered questions. Is this effect shared by all 5HT3 antagonists How does the effect of tropisetron compare to other steroids such as triamci-nolone or depomedrone Is there a bell-shaped dose-response...

Anticonvulsant Drugs

Anticonvulsant drugs (ACDs) have efficacy in mitigating neuropathic pain, including trigeminal neuralgia and phantom limb pain (McQuay et al. 1995), as well as migraine (Pappagallo 2003, Snow et al. 2002). As with the antidepressants, analgesic differences exist among the ACDs with regard to utility across types of pain conditions. Carbamazepine is Food and Drug Administration (FDA)-approved for the treatment of trigeminal neuralgia gabapentin, for treatment of postherpetic neuralgia pregabalin, for postherpetic neuralgia, diabetic neuropathy, and fibromyalgia (Crofford et al. 2005) and divalproex sodium and topiramate have both been indicated for migraine prophylaxis. General uses neuropathic pain, headache, poststroke pain, thalamic pain, fibromyalgia, irritable bowel (diarrhea type), and chronic pelvic pain with or without comorbid depression anxiety Pain-related FDA approvals none available for any of the TCAs General uses neuropathic pain and fibromyalgia Pain-related FDA...

Neuronal Plasticity

A characteristic feature of FMS is hyperalgesia (increased sensitivity to mechanical, thermal, and electrical stimuli) and allodynia (painful response to normally non-noxious stimuli). These are likely to be due to altered mechanisms within the CNS such as wind-up and central sensitiza-tion which have been demonstrated in FMS patients.49, 50 Altered pain processing has been illustrated by studies using functional magnetic resonance imaging (fMRI) where painful pressure stimuli result in increased cerebral blood flow in areas associated with activation by noxious stimuli. This is exaggerated in FMS patients at stimulus intensities that may otherwise be seen as non-noxious.51 High levels of catastrophizing were also associated with increased activity in similar areas,52 as was depression.15 (See Table 42.1.) Neither catastrophizing nor depression affects hyperalgesia, therefore other mechanisms must also be involved in fibromyalgia.52,53 observed that pain catastrophizing is higher in...

Patient selection

There are various demographic characteristics of patients enrolled in clinical trials that must be routinely assessed, not only to accurately determine inclusion and exclusion criteria but also for use in data analyses. Depending on the condition being examined, age (e.g. in postherpetic neuralgia), sex (e.g. in fibromyalgia), and other demographic and clinical (e.g. pain duration) characteristics may be important co-variates in analyses of the data. Education, occupation, employment status, workers' compensation and other benefits, and presence of any litigation may also play a role in treatment outcome.