Purinergic system, microglia and neuropathic pain

Extracellular nucleotides play pivotal roles in the regulation of neuronal and glial functions in the nervous system through P2X receptors (P2XRs) and P2Y receptors (P2YRs). A growing body of evidence shows that microglia express several subtypes of P2XRs and P2YRs, and that these receptors play a key role in pain signaling in the spinal cord under pathological conditions, such as following peripheral nerve injury (neuropathic pain). Following peripheral nerve injury, dorsal horn microglia become activated and show upregulated expression of purinergic receptors, and interference with the function or expression of these receptors strongly suppresses neuropathic pain. This article highlights recent advances that further increase our understanding of the mechanisms by which microglial purinergic receptors contribute to the pathogenesis of neuropathic pain.

► Peripheral nerve injury increases expression of purinergic receptors in microglia. ► Purinergic signaling is required for microglial functions. ► Microglial purinergic signaling contributes to dorsal horn neuron hyperexcitability. ► Microglial purinergic signaling contributes to neuropathic pain after nerve injury. ► Microglial purinergic receptors are potential targets for treating neuropathic pain.