Pathological and protective roles of glia in chronic pain

Abstract

Pain processing involves neurons, microglia and astrocytes. The functions of glia extend beyond basic support for neurons. Once activated, they release various classic immune factors that are also neuroactive substances. Glia express receptors for neurotransmitters and neuromodulators, so they can respond to neural activity. Despite the integral part that glia play in neuronal communication, most of the drugs that are available for treating pathological pain in humans target neuronal mechanisms. This may be one reason for their limited therapeutic efficacy in pain control. Early evidence from preclinical studies with animal models of neuropathic pain suggest that shifting glial activation from a pro-inflammatory to an anti-inflammatory state may prove to be important in clinical pain phenomena. Activated glia exert crucial neuroprotective and anti-inflammatory effects. Identifying ways to regulate the switch between the proinflammatory and the anti-inflammatory state of glial activation, rather than simply blocking glial actions, could be key to the development of more powerful strategies to treat clinical pain.