How microglia contribute to the induction and maintenance of neuropathic pain

Neuropathic pain is a debilitating condition caused by damage to the nervous system that results in changes along the pain pathway that lead to persistence of the pain sensation. Unremitting pain conditions are associated with maladaptive plasticity, disruption of neuronal activity that favours excitation over inhibition, and engagement of immune cells. The substantial progress made over the last two decades in the neuroimmune interaction research area points to a mechanistic role of spinal cord microglia, which are resident immune cells of the CNS. Microglia respond to and modulate neuronal activity during establishment and persistence of neuropathic pain states, and microglia–neuron pathways provide targets that can be exploited to attenuate abnormal neuronal activity and provide pain relief. Neuropathic pain caused by nerve damage results in neuronal pathway changes and immune cell engagement. In this Review, Malcangio and Sideris-Lampretsas discuss how microglia respond to and modulate neuronal activity and suggest that microglia–neuron pathways offer novel approaches for the attenuation of neuropathic pain.