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Cambridge University Science Magazine
Chronic pain is a medical condition that’s both debilitating and poorly understood. New research in mice, published in Nature Neuroscience a few months ago, has revealed more about how this type of pain is detected – and that it matters whether the mice are male or female.

In mouse models of chronic pain, microglia cells in the spine are thought to react to tissue or nerve damage, with effects including hypersensitivity to mechanical stimuli. Previous studies provided convincing evidence for this ‘glia hypothesis’: give a drug interfering with glial function to mice with hypersensitivity, and the mice are cured.

...If, that is, the mice are male.  Sorge and colleagues, who performed the Nature Neuroscience study, had noticed that all the experiments supporting the glia hypothesis were done in male mice. When they tried the same drug on female mice with the same condition, it didn’t work, suggesting that something other than microglia was involved. This mystery player turned out to be circulating immune cells - particularly T cells. What’s more, female mice could switch to the ‘male’ signalling method if necessary: when the researchers gave females testosterone, or depleted their T cells, the microglia-inhibiting drug started to work again.

Importantly, this study was only concerned with sex differences in the detection of chronic pain, not its perceived intensity. What is certain, though, is that researchers studying chronic pain can no longer use male and female mice interchangeably. If a similar difference shows up in humans, it would also be important when designing potential therapies for chronic pain. For example, a drug targeting spinal microglia might work for men, but not necessarily for women. The mice with chronic pain are a useful reminder that males and females often use different biological pathways to achieve the same result.

(Read the full article on the Nature website here.)