Spinal Microglia in Neuropathic Pain Plasticity

Abstract

Neuropathic pain affects a growing number of people worldwide, arising from a diversity of causes including traumatic nerve injury, neurotoxic chemicals or diseases that affect peripheral nerves, such as diabetes, HIV/AIDS and cancer. Despite these varying causes, it is clear that a principal cause of neuropathic pain is pathological alterations in the balance of excitation and inhibition in dorsal horn of the spinal cord resulting in hyperexcitability and enhanced activity in central nociceptive networks. It is the neuropathology that must be targeted for effective therapy of which there is none presently available. The focus of understanding of neuropathic pain mechanisms has been on neuronal processes that produce lasting enhancement of excitation or suppression of inhibition. There is, however, growing evidence that critical cellular processes are not restricted to neurons in the dorsal horn. Rather recent findings demonstrate involvement of glia, and of glia-neuronal signaling, in initiating and sustaining enhancement of nociceptive transmission. In particular, a role has emerged for microglia in pain hypersensitivity following nerve injury. Thus, an expanded understanding of cellular and molecular signalling mechanisms in the dorsal horn that will provide a basis of creating new types of strategies for management, and also for diagnosis, of neuropathic pain needs to include both neurons and glia.