Pain: It’s complicated

Pharmaceutical companies are knocking themselves out trying to find new pain relievers. So far, they aren’t having much luck. Pain is complicated and not fully understood. Bear in mind that pain is a crucial survival mechanism. It keeps us from harming ourselves. Case in point: word got out to pain researchers that a boy from Pakistan was entertaining tourists by sticking knives through his arms and walking across burning coals. He could do this because of a genetic abnormality called congenital insensitivity to pain (CIP). That is, his pain-sensing neurons were ineffective. Before the researchers could study him, he’d jumped off a building and died. He might have felt no pain, but he was not immune to death.

At the opposite end of the pain spectrum is the “man on fire” syndrome: searing, excruciating, pain in response to mild warmth—as mild as walking into a 68-degree room. In this case, the pain-sensing neurons are hyperactive. In both these extreme cases—hyperactivity and insensitivity—the same gene is implicated. Both cases also are variations of the ordinary pain we all experience when we’re injured or sick: the pain is caused by the activation of peripheral neurons that send their pain signals up our spinal cords and into our brains. This type of pain falls into the acute category.

The other category is persistent pain, characterized by chronic burning, deep aching, and electric shock-like sensations. Its mechanism is completely different from acute pain and is caused by cells in the brain called glia, which function as a kind of glue to hold neurons in place, but which also, as scientists have recently learned, supply them with nutrients and oxygen, insulate one neuron from another, and destroy pathogens. Unfortunately, they also promote an exaggerated pain response by enhancing neuronal firing when stimulated by a variety of triggers, such as a protein sent from sensory neurons following an injury. They’re also triggered by immune cells sent to the brain by the central nervous system’s lymphatic system.

Researchers are now recognizing that glial cells are probably implicated in inflammatory diseases such as rheumatoid arthritis and osteoarthritis. They’ve also discovered that women are more prone to persistent pain than men, but they haven’t figured out why. What’s more, opioid drugs are not useful—and can be harmful—in persistent pain.

As my source, The Scientist online magazine says, “…persistent pain is a very complex, multicellular disease state.” So far, there’s not much on the horizon in the way of help.

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