Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury

Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to n...

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Veröffentlicht in:Cell reports (Cambridge) 2015-11, Vol.13 (6), p.1246-1257
Hauptverfasser: Petitjean, Hugues, Pawlowski, Sophie Anne, Fraine, Steven Li, Sharif, Behrang, Hamad, Doulia, Fatima, Tarheen, Berg, Jim, Brown, Claire M., Jan, Lily-Yeh, Ribeiro-da-Silva, Alfredo, Braz, Joao M., Basbaum, Allan I., Sharif-Naeini, Reza
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Sprache:eng
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Zusammenfassung:Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to neuropathic pain, the molecular and cellular mechanisms underlying this disinhibition are unclear. Here, we combined pharmacogenetic activation and selective ablation approaches in mice to define the contribution of spinal cord parvalbumin (PV)-expressing inhibitory interneurons in naive and neuropathic pain conditions. Ablating PV neurons in naive mice produce neuropathic pain-like mechanical allodynia via disinhibition of PKCγ excitatory interneurons. Conversely, activating PV neurons in nerve-injured mice alleviates mechanical hypersensitivity. These findings indicate that PV interneurons are modality-specific filters that gate mechanical but not thermal inputs to the dorsal horn and that increasing PV interneuron activity can ameliorate the mechanical hypersensitivity that develops following nerve injury. [Display omitted] •Parvalbumin (PV) neurons of the dorsal horn synapse onto PKCγ excitatory neurons•After nerve injury, many PV-PKCγ synapses are lost and touch stimuli become painful•Specific activation of PV neurons after nerve injury alleviates mechanical pain Improved therapy for neuropathic pain requires a better understanding of the spinal cord neuronal networks that process peripheral sensory inputs in health and disease. Petitjean et al. find that a subset of inhibitory interneurons, containing the marker parvalbumin (PV), prevent touch inputs from activating pain circuits. After nerve injury, a decrease is seen in the number of these synapses, and light touch can elicit pain.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2015.09.080