“A person’s past experience of pain often impacts a person’s current response to painful stimuli,” says Robert Coghill, PhD, assistant professor in neurobiology and anatomy at Wake Forest University School of Medicine. For example, a man in Dr. Coghill’s study who had been stung many times during his years as a beekeeper did not feel as much pain as others in the test group when all received a stimulus that felt like a bee sting. The beekeeper’s experience with stinging decreased the pain he felt from a similar sensation years later.

Learning how the brain processes pain signals may be a key to understanding why people respond to pain differently. Researchers are just discovering that one reason pain becomes chronic is because of a “memory imprint,” in which the pain experience is recorded in the CNS and can contribute to ongoing pain. Neurons in the CNS might remain hypersensitive for long periods and respond in an amplified way. 

Using imaging technology, Dr. Coghill found that of the 17 patients in his test group, all of whom received the same pain stimulus, those who were highly sensitive to pain had frequent activation in regions of the brain involving the processing of pain. The people who reported less pain had minimal activation in those areas of the brain. Could this be due to individual past experiences? 

Individual differences may make sense, but what about gender differences? Why are more women than men affected by arthritis or fibromyalgia, and why do women often seem to experience more intense pain from these conditions? Researchers now know the pain sensory neurons that detect injury differ by sex. A woman’s pain sensory neurons tend to be highly refined, receiving more pain signals than a man’s. Estrogen receptors amp up the signaling of pain pathways, and researchers now believe this may contribute to women reporting more pain.

Amazing Maze

The “ouch” type of pain – which protects us from danger by letting us know when, say, a pot on the stove is too hot – involves a dedicated high-threshold, high-speed pain pathway starting at the site of the pain, shooting its way to and through the spinal cord and ending in the brain, all within a split second. In contrast, inflammatory pain such as arthritis pain develops when neurons in the CNS and PNS become hypersensitive, says Dr. Woolf.

“Multiple chemicals interacting at the site of inflammation – including cytokines such as tumor necrosis factor-alpha (TNF-a) – act on peripheral “pain-sensing” neurons and sensitize them,” says Dr. Woolf. Studies show that in people with RA, the nerve fibers within the joints become hypersensitive with repeated stimulus and then require only the smallest stimulus to create severe pain – a phenomenon called peripheral sensitization. 

Pain arising from changes within the CNS is referred to as central sensitization. “If the pain pathway in the spinal cord is excessively activated, for example in response to injury or tissue damage, the central pathway becomes hypersensitive so that neurons begin to respond to things that normally wouldn’t activate them, like light touch, vibration, movement of a joint or even just rubbing the skin,” says Dr. Woolf.