A state-of-the-art perspective on microgliopathic pain

Acute nociceptive pain is an undesirable feeling but has a physiological significance as a warning system for living organisms. Conversely, chronic pain is lacking physiological significance, but rather represents a confusion of nerve functions. The neuropathic pain that occurs after peripheral nerve injury (PNI) is perhaps the most important type of chronic pain because it is refractory to available medications and thus remains a heavy clinical burden. In recent decades, studies have shown that spinal microglia play a principal role in the alterations in synaptic functions evoking this pain. It is also clear that the P2X4 receptor (P2X4R), a subtype of ionotropic ATP receptors, is upregulated exclusively in spinal microglia after PNI and plays a key role in evoking neuropathic pain. Neuropathic pain is caused by several conditions associated with activated microglia without nerve damage. 'Microgliopathic pain' is a new concept indicating such abnormal pain related to activated microglia.