Mechanisms of Plasticity of Inhibition in Chronic Pain Conditions

The balance between inhibition and excitation in the dorsal spinal cord plays a critical role in ensuring that sensory information is relayed accurately to the brain. In particular, a loss of inhibitory control, and the ensuing increase in excitability in spinal dorsal horn neuronal circuits, appears to be a key substrate of pain hypersensitivity. In this Chapter, we summarize the most current knowledge on the involvement of altered GABA and glycine-mediated inhibition in pathological pain. Particular emphasis has been given to the recent finding that altered intracellular chloride homeostasis in neurons of the superficial dorsal horn may explain how inhibition is impaired following peripheral nerve injury and how this may underlie the development of neuropathic pain syndromes. Of particular interest is the finding that this mechanism of injury-induced central disinhibition results from a neuroimmune interaction involving a neuron-to-microglia-to-neuron signalling cascade.