Role of molecules expressed in spinal microglia in neuropathic pain

Physiological pain is an essential experience that alerts us to the presence of external or internal stimuli that are damaging or are potentially tissue-damaging. By contrast, pathological pain is not tied to the presence of tissue-damaging stimuli. One type of pathological pain-neuropathic pain-is often a consequence of nerve injury or of diseases such as diabetes, HIV AIDS or cancer, that damage peripheral nerves. Neuropathic pain can be agonizing, persistent over long periods, and, unfortunately, is often resistant to known pain-killers. Recent advances in our understanding of the mechanisms producing neuropathic pain have been made by defining causal roles of spinal microglia in the pathogenesis of neuropathic pain as several molecules including P2X ₄ receptors, which are present in activated microglia, have been found to be required molecular mediators. We expect that understanding the key roles of these molecules in spinal microglia may lead to new strategies for the management of neuropathic pain, strategies not previously anticipated by a neuron-centric view of pain plasticity in the dorsal horn.