Neuropathic pain, a chronic pain condition following nerve damage and degeneration, involves aberrant excitability in the dorsal horn of the spinal cord. A growing body of evidence has shown that the aberrant excitability might not be a consequence merely of changes in neurons, but rather of multiple alterations in glial cells, such as microglia, the immune cells of the central nervous system. Extracellular nucleotides play an important role in neuron-microglia communication through purinergic P2X and P2Y receptors expressed in microglia. Importantly, inhibiting the function or expression of these microglial molecules suppresses aberrant excitability of dorsal horn neurons and neuropathic pain, suggesting a crucial role for microglial purinergic signaling in mechanisms of neuropathic pain. Here, we describe recent advances in the understanding of neuron-microglia interactions by purinergic signaling in neuropathic pain following neurodegeneration. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'.
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