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Make it stop: New frontiers in pain research offer hope

A Stanford anesthesiologist is working to understand why pain becomes agonizing and chronic by examining the role of cells known as microglia.

Stacey Morris didn't mean to overdose. She'd been taking prescription pain medications following a surgery six months earlier to remove some calcium deposits from her right shoulder. Instead of subsiding as pain normally should after surgery, her pain had grown into a monster that tormented her all day, every day. Then, one night she happened to take her pain medication -- gabapentin -- along with a common sleep medication and a small glass of wine. The combination nearly ended her life.

In her story for the latest issue of Stanford Medicine magazine, Nicoletta Lanese recounts the decade-long struggle with pain experienced by Morris -- whose name was changed for this story -- and the work that her doctor at Stanford, Vivianne Tawfik, MD, PhD, is doing to understand and stop chronic pain.

Lanese gives a vivid description of what patients like Morris commonly experience:

The classic symptom of complex regional pain syndrome is long-lasting pain that is stronger than expected given the injury that triggered it. Other symptoms include muscle tremors and weakness, brittle nails, slow-growing hair, swelling, redness or unexplained warmth in the affected limb. Those with the syndrome may become hypersensitive: A minor cut or bruise might cause severe pain while normally painless sensations, such as feeling clothing against their skin, can become excruciating. For instance, when Morris walks on pebbles with bare feet, it can feel as if she's walking on jagged shards of glass.

Tawfik is working to understand complex regional pain syndrome by focusing on microglia, a type of cell found in the brain and spinal cord, that can amplify pain. She's made encouraging progress, learning that, in the mice she has studied, altering the microglia, even temporarily, can have dramatic effects. As the article describes:

By disabling or deleting 25 percent or more of a mouse's microglia, Tawfik can block their abnormally strong pain response before it takes hold. When she allows the mice's microglia to increase back to a normal level, they're still fine. It seems Tawfik may be flipping pain's off switch.

Those early results are encouraging, especially to women like Morris, for whom an alternate treatment might do more than bring relief; it could be lifesaving. That's because women between the ages of 45 and 54, writes Lanese, have the highest risk of dying from a prescription painkiller overdose. And even though, chronic pain affects far more women than men, the overwhelming majority of pain studies have been conducted on male mice, the article points out. Tawfik's studies tip the scale in the other direction, focusing on female mice.

For Morris, results can't come soon enough. As she manages her days with medication -- while managing the side effects and risks that go with them -- she, like Tawfik, looks to a day when a new therapy could change the course of pain treatment.

"I keep trying to find ways to be optimistic -- that's the hard part," Morris said. "I don't want to think that I won't get better."

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