Pain itself has two major divisions: neuropathic and nociceptive. Neuropathic pain is caused by injury to the nervous system, such as nerve pain associated with diabetes or shingles. It is typically treated with antidepressants, anticonvulsants, antispasmodics, anesthetics and adrenergic blockers. 

Nociceptive pain results from injury to tissues outside the nervous system, such as a cut on your skin, pain after surgery or the chronic pain of arthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, muscle relaxants, local anesthetics and opioids are used to treat nociceptive pain. Sometimes pain can be a mix of both types, such as a headache or a herniated disc in the back, requiring mixed treatments. Other times the source of pain remains a mystery, but researchers continue to sleuth.

Mean Genes

Working at the molecular level, researchers isolating genes associated with pain are finding that certain genetic predispositions may make people more or less susceptible to developing pain syndromes, says Dr. Woolf.

Genes control the type and amount of proteins produced by cells, and proteins affect cells and tissues in a variety of ways, from acting as enzymes that speed up metabolic reactions to inhibiting the metabolic pathway. Genes associated with pain can produce higher or lower levels of proteins, with dramatic effects on cells and tissues. One example, says Dr. Woolf, is stimulation of the enzyme cyclooxygenase-2 (COX-2), which leads to the production of prostaglandins, which, in turn, promote pain. “People are born with genes that control the level of pain they experience, but the level of proteins being expressed by those genes can be turned upward or downward by diseases,” says Dr. Woolf.

Researchers are beginning to find genetic underpinnings in fibromyalgia, partly explaining why it tends to run in families. And fibromyalgia is teaching researchers important lessons about pain. “If someone has the genetic propensity toward fibromyalgia and experiences stress – anything from an infection to physical trauma to emotional stress – the combination figures into the development of the condition,” says Daniel Clauw, MD, professor of medicine at the University of Michigan and a leading researcher on fibromyalgia pain. 

How exactly a stressor figures into the development of fibromyalgia remains to be determined, he says. “Evidence shows that fibromyalgia is not a psychiatric disease and is not depression; it’s something totally different,” says Dr. Clauw. Is that “something” partly a genetic factor? Possibly, but genetic research relating to fibromyalgia will take years, he explains. “Fibromyalgia differs from diseases like RA or lupus because it is more a disorder of the central nervous system than of the immune system. Proteins of the immune system circulate in the blood, so they can easily be tested. But nervous system proteins don’t circulate, so testing them is tough.”

Sex and Sensitivity

In addition to genetic scripting, the ways that people respond to pain depend on a range of factors, including cultural influences, past experiences and perhaps even gender, say researchers. As a result, the expression and experience of pain varies widely and is subjective. Culturally, some people are encouraged to vocalize when they are feeling pain; other societies promote stoicism. Society may be one factor that molds you; your life experiences are another.