Pain and suffering are especially resistant to definition because they are plural concepts. The history of pain is a record of pain's multiple re-inventions.50 The English word "pain'' refers to innumerable different experiences linked together not by a common essence (or by an immutable shared core) but by what philosopher Ludwig Wittgenstein calls "family resemblances'' (cited in Ref. 51). Pain (an abstract concept) exists only through concrete, multiple, and very distinctive pains. Even if we exclude metaphorical applications of pain to unhappiness and disappointment, as when coaches talk about the agony of defeat, it is now clear that the pain of migraine differs from cancer pain, that cancer pain differs from the pain of arthritis, that arthritis pain differs from the pain of fibromyalgia. Such differences go beyond variations in the quality, length, and intensity of sensation. They may correspond to distinctive biological processes and to particular experiences. As neuroscientist Tony Yaksh said in 1992, "At this moment, we're becoming just barely sufficiently sophisticated to say that all pain is not the same, and therefore to know why some analgesics may be very effective in some pain states and less effective in others. We need to learn the precise nature and mechanism of all the pain producers'' (cited in Ref. 52).
The invention of pain medicine rests upon an awareness that pain is never a simple unity. The centers and clinics emerging in the late 1960s and the 1970s were mostly committed to a bedrock distinction between acute and chronic pain. The distinction is not trouble free, but the basic principle won rapid acceptance. Chronic pain differs in kind - not in degree - from acute pain, and neither holds its traditional status as a symptom. Ronald Dubner, another neuroscientist who focused on pain, summed up changes that constitute a thorough challenge to traditional biomedical thinking. "We know now that pain is not merely a passive symptom of disease,'' he stated in 1992, "but an aggressive disease in itself, producing changes in the brain that underlie the pathology of persistent or chronic pain'' (cited in Ref. 52). Soon it became necessary to abandon even the ancient medical truism that nobody ever died from pain. Psychologist John Liebeskind showed in laboratory animals that pain depresses the immune system and destroys cancer-fighting cells. As the title of his seminal essay puts it bluntly, "Pain can kill.''53
The specific syndromes discussed in the IASP Classification of chronic pain tabulate almost as many kinds of pain as there are strains of roses, from the steady sharp or throbbing ache of gout to the sudden severe stab of tri-geminal neuralgia.22 There is visceral pain in the neck, chest pain, vascular disease of the limbs, abdominal pain of neurological origin, pain in the bladder and rectum, lumbar spine syndromes, pain syndromes of the hip and thigh, musculoskeletal syndromes of the leg, and multiple pains of the foot, as well as burns to the skin, arthritis in the joints, nerve damage, and lesions to the central nervous system (called central pain). There is stiff man syndrome, sickle cell arthropathy, and the pain of acquired immunodeficiency syndrome (AIDS). No single sensory process underlies all these diverse forms of affliction, but the last place where most patients would expect to find a common source for their pains is in a region devoid of sensory neurons. This, however, is exactly the paradox that neurosurgeon John Loeser confronts us with. "The brain,'' he writes, "is the organ responsible for all pain. All sensory input, including nociception, can be altered by conscious or unconscious mental activity.''54 The brain is also the putative generator of the placebo and nocebo effects (see Chapter 41, Placebo and nocebo in the Practice and Procedures volume of this series). The cerebral location of these effects is not yet known, but it is reasonable to suppose that they are related to the reward-aversion curcuitry. Study of reward-aversion functions is a fruitful area of basic reseach.55 Pain is typically aversive, and analgesia (particularly via opioids) seems to be rewarding. These circuits are not pure as other functions are also subserved. Pain and pain relief are thus possibly entangled with such reward-aversion functions as probability assessment, reward-intensity evaluation, motivationally salient stimuli, and cognitive/emotional outcome prediction.
The brain, as the organ responsible for all pain, holds a dual function. One function is biological and internal. The brain is crucial not only to the cortical activities that process nociceptive impulses from the periphery, but also to painful experiences generated in the absence of noci-ceptive input. You do not need a leg to feel pain in your leg - as patients with phantom limbs know, all you need is a working brain. The other function of the brain connects us with the external, interpersonal world of human culture. In effect, the brain is a natural interface between culture and biology. Your pain and my pain (even when evoked by nearly identical tissue damage) may differ significantly owing to variations in our social backgrounds and personal histories, including differences in our individual memories, beliefs, and emotional states.
The multiplicity of pain and suffering has no clear limit because our brains situate us within an open-ended matrix of biology and culture.56 Gender, for example, plays a significant role in pain. The relationship between gender and pain is complex, since identifiable patterns change with different medical conditions and across the life cycle.57 Men and women, however, show quantitative differences in sensitivity to pain and to analgesia that suggest differences in neural processing. Women also compose the majority of chronic pain patients, although it is unclear whether women face greater risk of pain or merely use healthcare services more often.58 Women are certainly more likely to experience a variety of recurrent pains, to report more severe levels of pain, more frequent pain, and pain of longer duration.59 While good evidence suggests that females exhibit greater sensitivity to noxious stimuli than do males, other studies suggest that women are better at coping with discomfort and that they complain less over time.60 Biological differences are important in this gender-influenced pain. Kappa opioids work twice as well for women as for men.61 Migraine affects about 6 percent of men and 15-18 percent of women.62 (The diminished frequency of migraines during pregnancy suggests a link with estrogen.) A significant implication of this research on gender differences in pain is that we should also expect gender differences in suffering. Women are overrepresented among battered spouses, whose suffering often combines physical injury with emotional trauma. A woman's position as caregiver in dysfunctional or chaotic families also suggests that suffering may be inflected by the social distribution of gender roles. Social beliefs about gender certainly affect clinical decisions regarding pain treatment.63 We should expect that suffering too, both inside and outside medical contexts, will reveal significant biocultural differences associated with gender.
The multidimensional quality of pain and suffering -situated within cultures, as well as within nervous systems - implies a need to resist the temptation to eliminate from research and from treatment all the messy local variations that come with living in societies. Low back pain is simply not the same experience in the USA as it is in Japan. In one study, Japanese patients proved significantly less impaired in psychological, social, vocational, and avocational function.64 Research comparing ten American cancer patients with ten cancer patients from India found significant differences in quality of life and in the meaning of the pain experience.65 Indian patients, who sought medical assistance only after their pain became intolerable, saw their suffering as the fulfillment of a "higher good,'' whereas American patients interpreted their own suffering as a form of "punishment.'' The authors of a review article focusing on numerous cross-cultural investigations conclude that more such studies are needed to explore the diverse "social and psychological variables that govern pain perceptions, beliefs, and reactions.''66 The culture-inflected character of pain is well illustrated in the reflections, commentaries, and essays collected in the Canadian-American anthology When pain strikes, with its self-conscious resolve to speak from and to the condition known as postmodernity.67 In one sign of postmodern change, researchers are increasingly interested in relations between the religion/spirituality dyad and the trio of physical health, mental health, and pain.68 One study of predominantly white, Christian, mid-western patients with chronic musculoskeletal pain produced some surprising information. Pain patients' religious and spiritual beliefs appeared different from the beliefs of a healthy population. Private religious practices, such as prayer and meditation, were inversely related to physical health outcomes. Patients experiencing worse physical health were more likely than less-challenged patients to engage in private religious activities, perhaps as a coping mechanism. The longer time that patients had been living with pain, the less "forgiving'' they were, and the less support they received from their church community. Such patients tend to lose hope, become bitter, grow angry at themselves, at society, and at God. Forgiveness, negative religious coping, daily spiritual experiences, religious support, and self-rankings of religious/spiritual intensity significantly predicted mental health status.
Suffering and pain are persistent features of human life, but they are not timeless or placeless states. They can involve specific churches and local communities, as well as widely shared genes and neurons. We cannot fully understand them apart from an awareness of how the human brain situates us inescapably within the modifying environments of a particular time and place, and culture.
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