Neuropathic pain decoded by microglial heterogeneity

Lesion or diseases affecting the somatosensory system causes neuropathic pain, a debilitating chronic pain condition. Previous studies using its experimental models have demonstrated the critical contribution of microglia to the development of neuropathic pain. Upon sensing nerve damage, spinal cord microglia alter their morphology, gene expression and function, which lead to an increase in the excitability of pain-transmission neural pathway, causing the pain onset. Recently, newly identified CD11c-positive microglia as a subset that increases during the remission phase of neuropathic pain has been shown to be required for spontaneous remission of neuropathic pain and to play an important role in maintaining the remission state. Thus, these findings suggest that the functions and roles of microglia under neuropathic pain conditions are not one-dimensional but change during the onset, maintenance, and remission phases, and they also provide a clue to establish a new strategy to decipher neuropathic pain and other neurological diseases from the heterogeneity of microglia.