Not all patients with pain are the same. But what makes them different? Two pain medicine experts addressed that question in Tuesday’s session “Pain Perception and Treatment: We Are Not All the Same.” Pain perception is influenced by a variety of factors, including sex, hormones, stress and the presence of centralized pain. Research suggests that better attention to these differences may help make pain treatment more effective.

Subjective assessment of pain differs between men and women, and psychosocial and cultural factors associated with masculine and feminine roles can be attributed to the differences. But they are not the only factors, said Andrea L. Nicol, M.D., M.S., Assistant Professor, Department of Anesthesiology at the University of Kansas School of Medicine, Kansas City.

Andrea L. Nicol, M.D., M.S., says better attention to differences in people may help make pain treatment more effective.

“Physiologically, men are different than women in pain sensitivity,” she said.

Dr. Nicol explained that many pain syndromes occur only in women and other pain syndromes are more prevalent in women. In addition, the results of quantitative sensory testing have shown that women have a lower pain threshold and a higher pain sensitivity compared with men.

Hormones also have an impact on pain perception. High or low estrogen levels in women tend to enhance pain, while testosterone generally improves pain and quality-of-life measures. Additionally, functional MRI and PET findings show differences in pain processing between men and women.

Stress, trauma and abuse also have clinical implications for pain. A history of lifetime trauma is associated with chronic pain syndromes, and 28 to 71 percent of people with fibromyalgia report a history of trauma. The potential mechanisms for the relationship between stress/trauma and pain include dysregulation of the hypothalamic-pituitary-adrenal axis, central sensitization, changes in corticotrophin-releasing hormone circuits and alterations in brain morphology.

Dr. Nicol said that these findings have led her to ask different questions when evaluating patients with pain. For example, in addition to traditional questions, she asks about stress, extreme traumatic injury, war-related trauma and early life stress or abuse.

The presence of centralized pain also appears to play a role in pain perception, said Chad M. Brummett, M.D., Associate Professor, Department of Anesthesiology and Division of Pain Medicine at the University of Michigan Medical School. He noted a study in which the number of locations with pain problems was a significant and independent determinant of persistent pain after total knee or hip replacement. Differentiating pain that is more centralized could provide a mechanistic rationale for interventions, said Dr. Brummett.

To address this issue, he and his colleagues conducted research using a Total Fibromyalgia Survey, a combination of a symptom severity index (to score CNS-derived symptoms that accompany centralized pain) and a widespread pain index (to measure the number of areas of chronic pain). The score indicates a degree of “fibromyalgia-ness,” he said. Among patients who had a total knee or hip replacement, higher scores on the survey were associated with distinct differences in a preoperative pain phenotype. This consisted of such factors as severity of surgical site pain and overall body pain, duration of pain in the surgical site, neuropathic pain, depressive and anxiety symptoms, catastrophizing and positive affect. Each factor, except duration of pain, differed significantly between low, moderate and high scores.

In another study, Dr. Brummett found that the fibromyalgia survey score was a predictor of poorer outcomes after arthroplasty, even for patients who had a score that was well below the threshold for a diagnosis of fibromyalgia.

“We could be mechanistically treating patients incorrectly,” said Dr. Brummett.

To apply these findings to practice, Dr. Brummett said that a fibromyalgia survey score could help differentiate between patients who can proceed with an arthroplasty and patients for whom additional information should be sought and other therapies considered before the procedure is done.