Pain-Resolving Microglia

Neuropathic pain after peripheral nerve damage is a lasting condition that generally persists even when the cause of damage disappears (1). The immune system is integral to the development of neuropathic pain: In the spinal cord, microglia—the central nervous system–resident macrophages—respond to neuronal activity and set up a positive feedback loop with neurons that promotes pain onset. Thus, disruption of microglia-neuron communication is being considered as a strategy to produce analgesia. On page 86 of this issue, Kohno et al. (2) describe a spinal cord–resident pool of microglia that emerges during pain maintenance and contributes to the resolution of neuropathic pain in mice. Microglial heterogeneity is a well-accepted concept that is underexplored in the context of chronic pain (3). The finding that spinal cord microglia acquire spatial and temporal transcriptional heterogeneity that affects pain could identify new therapeutic strategies to relieve pai