Source: ScienceWeek
Date: 12 December 2003


The following points are made by Marcia L. Meldrum (J. Am. Med. Assoc. 2003 290:2470):

1) Pain is the oldest medical problem and the universal physical affliction of mankind, yet it has been little understood in physiology until very recently. The philosophical, political, and religious meanings of pain defined the suffering of individuals for much of human history. Pain is the central metaphor of Judeo-Christian thought: the test of faith in the story of Job, the sacrificial redemption of the Crucifixion. In the utilitarian dialectic of the 18th and 19th centuries, pleasure was balanced against pain to determine the good of society.

2) But pain was also a medical problem. European physicians did their best to relieve their patients' pain, most often through the judicious use of opium or, after 1680, laudanum, the mixture of opium in sherry introduced by Thomas Sydenham (1624-1689). But physicians also inflicted pain when necessary, to relieve evil humors or to amputate diseased limbs. The physician valued pain as a symptom, a sign of the patient's vitality, of the prescription's effectiveness. "[T]he greater the pain, the greater must be our confidence in the power and energy of life," one commented in 1826.(1) That men, women, and children endured physical suffering was inevitable; the meaning, rather than the fact of pain, was what mattered to the good life.

3) In the early 1800s, however, the utilitarian philosophy, with its emphasis on reducing the pain of the greatest number, combined with the new philosophy of individual rights and the Romantic poets' insistence on the importance of individual experience, gradually changed attitudes.(2) Was it not a positive good to relieve pain? The skilled surgeon took pride in his ability to operate rapidly, minimizing his patient's agony. But a few experimenters realized the possibilities of the sedative gases, particularly ether, often used as an analgesic for toothache. Following an unsuccessful attempt by his colleague Horace Wells, the American dentist William T. G. Morton (1819- 1868) gave his famous demonstration of anesthesia with ether on October 16, 1846. The British obstetrician James Young Simpson (1811-1870) proposed the use of chloroform in childbirth and surgery soon after, in 1848.(1)

4) The introduction of surgical anesthesia was one of the great revolutions of modern medicine, but not all physicians were immediately enthusiastic. There was an extended debate over the ethics of operating on an unconscious patient in both Europe and the US, a debate about the possibility that the relief from pain might actually retard the healing process. Religious writers called anesthesia a violation of God's law, whom they believed inflicted pain to strengthen faith and to teach the new mother the need for self-sacrifice for her children. But the surgeons could not long resist their new power to perform longer and more complex procedures, and most patients thought anesthesia a divine blessing. Still, for much of the mid-19th century, the practice was not universal. Physicians used a "calculus" to determine which patients were of the correct sensibility to need or benefit from the use of anesthesia.(1,3-5)

References (abridged):

1. Pernick MS. A Calculus of Suffering: Pain, Professionalism, and Anesthesia in Nineteenth-Century America. New York, NY: Columbia University Press; 1985

2. Morris DB. An invisible history of pain: early 19th-century Britain and America. Clin J Pain. 1998;14:191-196

3. Rey R. The History of Pain. Wallace LE, Cadden JA, Cadden SW, trans. Cambridge, Mass: Harvard University Press; 1993

4. Morris DB. The Culture of Pain. Berkeley: University of California Press; 1991

5. Schmitz R. Friedrich Wilhelm Sertürner and the discovery of morphine. Pharm Hist. 1985;27:61-74

J. Am. Med. Assoc.



The following points are made by J. Yang and C. Wu (American Scientist 2001 89:126):

1) Running parallel to its long history of misconception and misinterpretation is an almost 400-year history of legitimate scientific inquiry into pain's etiology and mechanism. Such considerations began with the 17th-century philosopher, mathematician and physiologist Rene Descartes (1596-1650), who first proposed a link between peripheral sensation and the brain. While contemplating the mind-body connection, Descartes suggested that sensations stimulated in the body are conveyed directly to the brain, where they are actually perceived. Although this view is now considered overly simplistic, that should not diminish Descartes's insightful realization that sensory perception is in fact a function of the brain. The Cartesian model gave rise to the notion of a "hard-wired system", where pain signals were carried by fixed connections within the nervous system. This idea was reinforced by anatomical studies conducted during the 19th century and has endured, with a few modifications, until fairly recently.

2) In the mid-1960s R. Melzack and P. Wall (Science 1965 150:971) challenged the notion of a hard-wired system with their view that sensory information undergoes dynamic integration and modulation. The current view of nociceptive pain (pain arising from tissue damage) derives from this idea. Neuroscientists now think of the nervous system as plastic. They no longer believe the relay of pain information to be based on an immutable relationship between a painful stimulus and the sensory output of pain. Rather, the perception of pain results from the integration of information from a variety of sources. Of course information is relayed from the injured tissue or organ in the periphery, but the strength of this signal can be modified by emotional and behavioral information coming down from the brain, as well as by inputs from other peripheral sensations. Furthermore, biologists now think that the integration of these signals actually takes place in the spinal cord, not in the brain, and that the integrated information is then carried up to the brain for further processing.

3) C. Woolf and M. Salter (Science 2000 288:1765) recently enumerated the three general levels at which neural information could be modified in response to chronic pain. They noted that the extent and duration of the response to the stimulus at the periphery could be modified. Alterations can also take place at a chemical level within any one or several of the neurons along the pain-conduction pathway. These include changes in the number or sensitivity of receptors, ion channels and internal signaling molecules. Finally, chronic pain can induce a modulation of the neurotransmitters that affect the flow of information from one neuron to the next, or it can even alter the anatomical features of these neurons and their interconnections. The set of alterations described by Woolf and Salter may lead to long-term changes in the connectivity and organization among nerve cells. This, in turn, may lead to a "pain memory", not much different from ordinary memory in the brain.

American Scientist



In mammals, including humans, the receptors for pain, called "nociceptors", are free nerve endings (i.e., endings not terminating on other neurons or muscle fibers or specialized sense receptors) found in almost every tissue of the body. These free nerve endings may respond to any type of stimulus if the stimulus is strong enough to cause tissue damage. When stimuli for other sensations, such as touch, pressure, heat, and cold, reach a certain intensity, they provoke the sensation of pain as well as the relevant primary sensation.

Excessive stimulation of most sensory receptors causes pain, but pain is also caused by excessive distension or dilation of a structure, prolonged muscular contractions, muscle spasms, inadequate blood flow to an organ, or the presence of certain specific chemical substances. For example, tissue injury releases chemical entities (e.g. prostaglandins and kinins [see below]) that stimulate nociceptors.

In general, pain persists even after an initial tissue trauma occurs, since these substances linger and nociceptors adapt to stimuli only slightly or not at all. Because of their sensitivity to all excessive stimuli, pain receptors perform a protective function as they respond to changes that might endanger the organism.

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