The Treatment of Pain

Clinically, pain can be described as a complex construct, integrating the physiologic, mechanical, and neurochemical responses with the social, behavioral, and psychological responses to noxious stimuli. It is therefore necessary to recognize myriad approaches to the treatment of pain and to assess and treat the patient within a larger biopsychosocial view. The choice of a given course of therapy for pain, therefore, is often more dependent on the beliefs of the caregiver and the prevalent world view of his/her place and time. Through history and continuing today, pain therapies have ranged from religious and spiritual practices, cognitive approaches, behavioral therapies, and pharmacotherapy, to highly anatomically specific treatment.

Physicians have long sought to categorize and form systematic means of understanding and addressing pain through the listing and classification of its causes. For example, during the time of the Roman emperor Trajan, who reigned from 98 CE until his death in 117 CE, 13 causes of pain were recorded. Avicenna, a noted Muslim healer and one of the early fathers of modern medicine, in the early 11th century described 15 separate causes of pain. Samuel Hahnemann, the founder of homeopathy, listed 75 (Fulop-Miller 1938). Despite these attempts at organization of pain etiologies, very few specific therapies for painful syndromes were utilized. Prior to the 18th century and the development of anatomical theories that could be clinically implemented in the treatment of pain, many nonspecific therapies were commonly used.

The view of the body as a representation of changes in the natural world, with energetic disproportions envisioned as the etiology of pain, required the development of treatments that would address these imbalances. Examples include the 4,000-year-old practice of acupuncture, which involves the insertion of needles at particular points or along particular meridians, which are then manipulated to either drive energies into or out of the affected system, thereby providing a direct revision of the imbalanced qi. Additionally, the application of humoral opposites (see Table 1.2), cupping, blood letting, purging, the use of topical and oral herbal compounds, and distraction by creating a competing, more severe pain, were all employed as means to return balance and alleviate pain.

The English word "pain" is derived from the Latin word poena, meaning punishment. It is then unsurprising that an early requirement for the relief of pain was through prayer (Parris 2004). This interpretation clearly reflects the idea of the painful stimulus as being harm inflicted by an omnipowerful presence in response to wrong doing. The iconography of tortured saints, with ecstatic faces, depicted pain as a spiritual discipline, primarily relieved by prayer, meditation, and righteousness.

The relationship between the psyche and the presence and importance of pain is not a new concept. Coping, learning, the role of anxiety, and concurrent psychiatric illness have all been identified as altering pain perception and success of pain therapies. In the 20th century, many new ideas in psychology emerged, which directly affected how pain is treated today. During World War II, Henry Beecher astutely noted that on the battlefield, seriously wounded soldiers reported less pain than civilian patients in the Massachusetts General Hospital recovery room. However, at a later time these same patients would complain vehemently about even minor physical insults. These observations caused Beecher to conclude that the experience of pain was derived from a complex interaction between physical sensation, cognition, and emotional reaction (Beecher 1946). In the 1950s, based on Freudian ideals, the link between psychiatric illness and pain was explored by Engel. By the mid-1960s, it was confirmed that chronic pain patients also often had coexisting psychiatric disease (Engel 1959) and behavior and cognitive therapies were emerging as rational alternatives to more traditional psychoanalytic thought.

The advent and advancement of pharmacological approaches to pain ultimately revolutionized the physician's capacity to provide a therapy that could yield direct relief. While pain-relieving drugs are alluded to in the writings of many ancient societies, the modern pharmacological treatment of pain has been mostly influenced by the cultivation of opioids. While it is not known precisely when in history the opium poppy was first cultivated, it is believed that the Sumerians isolated opium from its seed capsule by the end of the third millennium BCE and that its use spread along trade routes. Beginning in the 16th century, opioid abuse was identified in Turkey, Egypt, Germany, and England. Famously, Thomas Sydenham concocted the recipe for laudanum, consisting of opium, sherry, wine, and spices, in the mid-17th century, and it was quickly and widely employed to treat a broad range of ailments, from dysentery to hysteria and gout. In 1806, the active ingredient in opium was identified by Serturner, who dubbed it morphine after Morpheus, the god of dreams. Soon after, codeine was isolated (Brownstein 1993). Without the ability to inject medications, the routes of convenient administration of drugs were limited. This was revolutionized in the 1850s, following the development of the hypodermic needle by Rynd (1845) and the syringe by Wood (Mann 2006). In the years that followed, accompanying increased medicinal use of opiates, many attempts were made to synthesize a more potent, safer, less addicting alternative to morphine, yielding the development of heroin in 1898 and methadone in 1946 (Brownstein 1933).

Other classes of drugs still in use today take their roots in traditional medicines of antiquity. In South America, coca leaves were traditionally used as a remedy for altitude sickness, physical pain, and as a topical anesthetic. From the coca plant, the alkaloid anesthetic cocaine was isolated by Albert Niemann in the 1860s. Niemann touted the use of cocaine as a cure-all, including for treatment of alcohol and morphine addiction (Niemann 1860). Soon after, in 1884, Carl Koller demonstrated the local anesthetic effects of cocaine (Koller 1884). Additionally, nonsteroidal anti-inflammatory drugs are known to have been used in the form of myrtle leaf, a natural source of salicylates, by the ancient Egyptians. By 200 BCE willow bark, another natural source of salicylic acid, was in use by Greek physicians; however, the first scientific report of the power of willow derivatives was not published until 1763 by the Reverend Edmund Stone (Leake 1975). Salicylic acid was identified as the active ingredient in willow leaf extract by the French pharmacist Henri Leroux in 1829. A more palatable and well-tolerated version of the drug was prepared by Charles von Gerhardt in 1873 with the addition of an acetyl group, synthesizing what is commonly known today as aspirin (Fairley 1978). Quickly thereafter, in 1899, aspirin was registered and marketed by Bayer.

As the adage goes, "a chance to cut is a chance to cure," requiring that the medical caregiver believes that the nature of a pain lies in the body. Inspired by specificity theory and its derivatives, more and more refined specific anatomical treatments were developed for the treatment of pain, in both the peripheral and central nervous systems. Multitudes of surgical approaches to pain have been employed, predominantly based on the tenet of interruption of a specific path of sensory conduction, including neurotomies, dorsal root excision, thalamectomy, mesencephalic lesioning, psychosurgical lobotomies, and other procedures specifically designed to alter the anatomy and interrupt pain signal reception.

In addition to open surgical procedures, direct interventional approaches to the disruption of pain signals developed. As early as 1784, James Moore, a British surgeon, demonstrated that the compression of specific nerves could provide reversible surgical anesthesia, thereby piloting regional nerve blockade (Moore 1784). However, the use of injection of neurolytics to provide long-lasting interruption of nerve conduction was not performed until 1903 by Schloesser (1903). Later, in response to patients with sympathetic nerve injuries in World War I, René Leriche developed the technique of injecting the local anesthetic procaine and surgical sympathectomy, which later became a standard therapy (Leriche 1937). In the 1920s, nerve ablation procedures became a treatment of choice, even for chronic unexplained pain syndromes, cementing the role of nerve blocks, and in 1936, at Bellevue Hospital in New York City, the first nerve block clinic for pain management was established (Rovenstine 1941).

While electrical modalities for pain relief were used by the ancient Egyptians, Greeks, and Romans, typically by means of medical use of electric fish, the underlying explanation of how electricity caused pain relief was not explained until gate control theory became a part of the pain practitioner's lexicon (Sabatowski et al. 1992). Modern extrapolations of gate control theory now include implantable dorsal column stimulators, transcutaneous electric nerve stimulation (TENS) units, and deep brain stimulation.

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