The Pain Chronicles (19 page)

PAIN THRESHOLD AND PAIN TOLERANCE

Confusion about pain sensitivity continues, and many of its myths still exert a pernicious influence on patient care by justifying discriminatory treatment. Is there actually an invisible hierarchy of feeling? Or does the curse of
‘etsev
and
‘itstsabown
afflict all mortals equally?

Pain sensitivity is measured in three ways. The first measure is on a cellular level, where the
nociceptive threshold
marks the point at which a thermal (burning or freezing), mechanical (pinching or pulling), or chemical (poisonous or acidic) stimulus is sufficient to trigger the peripheral nerves (nociceptors) designed to sense cell damage. Because it is hardwired by evolution, the nociceptive threshold is common to all members of a species and can be altered only by disease processes, such as leprosy and diabetes, that eat away the peripheral nerves, causing local areas of numbness (called peripheral neuropathies).

A second measure of pain sensitivity is called simply the
pain threshold.
The pain threshold is a function of consciousness; it is the point at which the brain processes information from the nociceptors and perceives a stimulus as painful—for example, the sensation of pressure turns to the sensation of crushing pain or the sensation of warmth turns to the sensation of burning. Although it is not as uniform across a species as the nociceptive threshold, the pain threshold is also fairly similar from individual to individual.

The third measure of pain sensitivity—
pain tolerance
—accounts for the variability of what we can endure. Pain tolerance is commonly measured in experiments, for example, as the point at which a subject declares a painful stimulus unbearable and asks for it to be discontinued. Pain tolerance depends not only on the temperament of the individual but also on the circumstances of the pain. Not surprisingly, participants in pain studies have no particular motivation to suffer for the sake of an experiment, so their tolerance tends to be low; by contrast, the study’s conductors are very motivated to sacrifice in the service of their own work and therefore tend to discover that their own pain thresholds are high.

Yet the very participants who are quick to find a mild heat stimulus unbearable in a laboratory would respond quite differently if they had a compelling reason (or, indeed, any reason) to endure it—say, if they were rescuing their cat from a fire, or fire walking in a Hindu rite or a Western team-building exercise. Even in an experimental context, pain toleration varies with circumstances; subjects asked to hold their hands in icy water will endure it twice as long if they are not alone.

Is pain tolerance affected by gender, race, age, ethnicity, weight, or educational level? Are whites more sensitive than blacks, women than men, the slender than the stout, the fair-haired than the dark-haired, the young than the old, the educated than the ignorant? Clearly, different cultures respond differently to pain. A well-known study of housewives in the late 1960s found that in the United States, what were then known as “Yankees” (white Protestants of British descent) had the highest pain tolerance, followed by first-generation Irish, Jews, and, lastly, among those studied, Italians. (Interestingly, another paper found pain tolerance markedly increased for Jewish subjects with the presence of a non-Jewish, as compared with a Jewish, investigator.)

But perhaps the Italians being studied simply expressed more pain because their culture permits greater expressiveness, and since expressing pain can ease it, perhaps they actually suffered less. Indeed, a recent study by British researchers asked volunteers to hold their hands in painfully icy water; one group was allowed to continually swear aloud with a curse word of their choice, and the other had to repeat a non-swear mantra. The people who were allowed to swear were able to keep their hands in the water longer, and they perceived it as less painful. The testers theorized that the swearing induced a fight-or-flight response (release of stress hormones), which reduced fear of pain and therefore pain perception.

A benchmark 1972 Stanford University study, led by Dr. Kenneth M. Woodrow, of more than forty thousand patients belonging to a large HMO found that age, sex, and race do modify pain tolerance. Older men’s pain tolerance was two-thirds to three-fourths of that of younger men’s. In women, the decline was less pronounced, however, and even the oldest men had a higher pain tolerance on average than the youngest women. Pain tolerance, in general, varied less among women than men. Whites showed more pain tolerance than blacks, and blacks showed more tolerance than Asian Americans. Another study found Hispanics to be more sensitive to pain than non-Hispanic whites.

The Woodrow study made no claims as to whether the differences in pain toleration between ethnic groups are culturally or biologically determined. But the more that subjective differences in pain sensitivity are studied, the more frequently they appear to have a biological basis. Although the data is complicated and debated, numerous studies suggest (irritatingly) that nature may indeed be sexist and females simply have lower pain tolerance than males. Perhaps as an adaptive response to males as warriors and hunters sustaining more acute injuries than females, there seem to be differences in male and female pain-modulatory systems, with males enjoying more robust pain modulation. Female hormones are a potential mediator of the sex difference in pain sensitivity. Certain phases of the menstrual cycle are associated with a lower pain threshold.

There are interesting differences in male and female opioid receptors. (The differences are also present in male and female rats.) There are three types of opioid receptors, most notably
mu
and
kappa
; most opioid drugs such as morphine target mu receptors. Few drugs that target kappa receptors have been developed, because early trials found them ineffective. The research, however, was conducted largely on men, and it turns out that women are more responsive to kappa-receptor drugs. One study of a rarely prescribed kappa-receptor analgesic (nalbuphine) on postoperative pain in men and women who had their wisdom teeth removed found that the drug had opposite effects on the two sexes, ameliorating female pain and exacerbating male pain. Studies of mice suggest that the sex differences in the analgesic effect of kappa opioids could be traced to one gene, known as melanocortin-1 receptor, or MC1R.

The common mu-receptor analgesics, by contrast, are less effective in women than in men (and less effective in female rats than in male rats). A 2003 study by Dr. M. Soledad Cepeda and Dr. Daniel Carr of postsurgical pain following general anesthesia found that “women have more intense pain and require 30% more morphine [on a per-weight basis] to achieve a similar degree of analgesia compared with men.” The study advises that “clinicians should anticipate the differences in opioid requirement to avoid under-treatment of pain in women.” So although women are less likely to be prescribed opioids, they actually require more. There is also some limited evidence that women respond differently to nonsteroidal anti-inflammatory drugs (NSAIDs): although the drugs act equally on inflammation in both genders, men receive more analgesic benefit from the drugs than women do (a finding that may provide clues to why women suffer more from chronic inflammatory conditions).

Even the far-fetched Victorian notion that hair color affects pain sensitivity turns out to have a grain of truth in regard to fair-skinned redheads. A certain type of opioid pain medication that acts on kappa receptors (pentazocine) was found to work dramatically better for red-haired women; it turned out that the same gene MC1R that accounts for women’s responsiveness to kappa opioids is also responsible for red hair and fair skin pigmentation. Interestingly, common opioids work less well in redheads. Redheaded women need an average of about 20 percent more general anesthesia than dark-haired women. They also derive less analgesia from novocaine and are more likely to avoid going to the dentist.

Puzzlingly, studies prior to Dr. Woodrow’s agreed with the Victorian notion that the old are less pain sensitive than the young. But those studies employed thermal pain (heat or cold stimuli applied to the skin), whereas the Woodrow study employed mechanical pressure on the Achilles tendon (which produces a deep pain). Aging, it turns out, has contradictory effects on pain: sensitivity to cutaneous pain
decreases
, while sensitivity to deep pain
increases
(which is more clinically relevant because it more closely resembles the pain produced by disease processes and injuries than does a superficial stimulus). This finding may be of great value in developing analgesia for elderly populations.

Although Galen believed that fat, phlegmatic types had diminished pain sensitivity, the contrary seems to be true. Unsurprisingly, obesity creates pain-causing conditions, such as greater rates of degenerative arthritis, because of the extra weight that joints must support. (Degenerative arthritis, also known as osteoarthritis or wear-and-tear arthritis, involves a deterioration of the cartilage that cushions the bones at joints, which results in pain, stiffness, and inflammation.) But do the obese also suffer from lower pain toleration? Do painful stimuli actually hurt them more?

Many studies have shown that the obese
report
more pain in laboratory pain-toleration studies. But does this reflect a difference in their bodies’ innate pain sensitivity? A 2006 Ohio State University study attempted to answer that question by measuring the muscular response to electrical stimulation of a nerve in the legs of patients suffering from osteoarthritis of the knee. The obese patients reported no more pain than non-obese people (and rated their pain in a similar fashion in questionnaires). But their ankles demonstrated a greater muscular pain reflex. When all the volunteers were given a pain-toleration training session that included a progressive muscle relaxation exercise, both groups reported less pain and showed diminished pain responsiveness. But the obese continued to show greater pain sensitivity.

The view that children were not sensitive to pain continued to hold sway through the first half of the twentieth century. Many in the medical profession held that infants felt no pain at all and that young children were simply not developed enough to suffer. Until the late
1970s
(this is not a typo), most surgeries in the United States and around the world were performed on infants with little or inadequate anesthesia (although they were paralyzed with a neuromuscular blocker) because general anesthesia was believed to introduce unnecessary risk. Pain medication was also withheld from infants and young children during recovery from surgery, cancer, and even severe burns.

Even after the practice was recognized as harmful, anesthesiologists and hospitals resisted change. As late as 1987, an editorial in
The New England Journal of Medicine
still found it necessary to argue that the evidence was “so overwhelming that physicians can no longer act as if all infants were indifferent to pain.” Finally, a study conclusively demonstrated that babies who were operated on without anesthesia were more likely to die! By contrast, those given anesthesia recovered more quickly from surgery and suffered fewer complications.

Although pain generates less lasting
emotional
reaction in infants and young children than in older children and adults (hence children can emit bloodcurdling screams of pain at one moment and then laugh the next),
physiologically
, young children are much more adversely affected by pain because the nervous pathways that conduct pain develop earlier than the brain’s ability to modulate pain. While the ancient Assyrians were concerned enough about pain to asphyxiate their baby boys to the point of unconsciousness before circumcision, many infants today continue to be circumcised without anesthesia, even though the practice has been shown to have long-lasting detrimental effects.

A doctor who worked for the French pain-treatment charity Douleurs Sans Frontières (Pain Without Borders), found that physicians in Africa had to be trained to recognize pain. A pediatrician at a good hospital in Mozambique, for example, assured the French doctor that none of his patients had pain. He took him to the children’s ward to prove it. “You see,” he said, “none of the children are crying or fussing. They are lying quietly in their beds.” The French doctor had to explain that it is natural for children to cry and move about and that
not
crying can be a sign of terrible pain. Daniel Carr recalled a paper submitted to
Pain
, a professional journal he edits, in which a Chinese physician argued that children in China recovering from abdominal surgery were not given—and did not ask for—pain medication and concluded that Western children are wimps.

The Victorians were also right that race affects pain sensitivity—but in the opposite way from what they believed. African Americans are more hampered by chronic pain; they report suffering greater pain severity and disability in connection with a variety of pain-causing conditions. Moreover, this phenomenon holds true over a wide variety of age-groups and populations, including young children.

Part of the reason is now thought to lie in ethnic differences in pain-modulation systems. Although it has been extensively documented that African Americans have lower pain tolerance than whites in laboratory studies, the relevance of the finding has been unclear. Most of the studies relied on healthy volunteers, often college students. Acute pain and chronic pain are known to involve different physiological mechanisms: the nervous system of a healthy person may differ profoundly from that of someone with chronic pain. Moreover, the psychological experience of suffering from chronic pain is utterly unlike that of the test of acute pain in a lab, where subjects are explicitly reassured that they will not be hurt (and ethical guidelines require that tests be discontinued prior to tissue damage, even if the subject does not request it).