Recent advances in neuroimmune interactions in neuropathic pain: The role of microglia

Neuropathic pain is a debilitating condition that continues to challenge the clinic. This is largely due to the fact that current analgesics have limited efficacy and considerable side-effect profiles. A body of preclinical evidence supports a critical role of glial cells in chronic pain mechanisms, and remote damage in the peripheral nervous system has been shown to induce neuronal plasticity and changes in microglial and astrocyte activity. The release of glial-derived pronociceptive mediators such as ATP, cytokines and chemokines sensitise neurons via their cognate receptors, thereby contributing to central sensitisation and the resultant generation of allodynia, hyperalgesia and spontaneous pain. In this chapter we discuss the current evidence for the role of microglia, astrocytes and gliotransmitters in mediating spinal neuron-non-neuronal cell communication. Selective control of chemokine-mediated neuronal-glial interactions provides analgesic effects in rodent models of neuropathic pain and thus presents a potential avenue for therapeutic intervention.