One factor in gender differences in pain & rheumatic diseases … is the role the extracellular matrix plays as an interface between the immune system & the nervous system.
It would help clinicians, he said, to alter the way in which they think about chronic pain—it’s not how long the pain lasts, but the mechanism of it. Thinking in terms of pain duration “gives us no insight into the biology of this pain,” and, therefore, no insight into how to treat it.
Chronic pain, he said, can come in two forms: one that can last for months or decades, but disappears when you remove the underlying cause; and another in which patients feel pain even when they’re in “remission,” with no sign of inflammation or disease, or when a patient becomes resistant to a kind of therapy that used to work.
Gender Differences
For all its limitations, research has produced some striking illustrations of gender pain mechanisms.
A key gender difference, Dr. Levine said, is in the mechanism underlying “hyperalgesic priming,” a process that leads to chronic pain. But the stimuli and pathways involved in this process vary greatly between men and women. For example, certain inflammatory stimuli—such as TNF-alpha and IL-6—initiate the process in men, but not in women.
In male rats, when male sex hormones are removed, the mechanisms involved in sensitization in the nociceptor are unchanged. In females, they are very different, with a protein kinase C-epsilon pathway that doesn’t exist in those in which the sex hormones are intact.
Studies of gender differences in the effectiveness of analgesics have been scant, but one study of the kappa-agonist, nalbuphine—led by Dr. Levine—shows a striking disparity. Women on a 10 mg dose of the drug had pain levels improve dramatically and continue to be improved; however, in men, the drug led to some relief at first, but ultimately resulted in worse pain levels than baseline.
Further study found that a mix of 5 mg of nalbuphine and 0.4 mg of naloxone led to pain relief that was similar in both men and women. This indicates that a completely separate receptor is at work in men, Dr. Levine said.
“There’s a second receptor that these drugs work in that makes pain worse,” he said. “Dramatically different between men and women.”
Dr. Levine expressed wonder that 5,000 years after opioids began to be used for pain relief, we only began to recognize gender differences about 20 years ago. Even now, he said, there is still an element of “it’s all in your head,” when it comes to women and pain, he said.
