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Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
The neurobiology of persistent pain and its clinical implications
1Department of Biomedical Sciences, University of Maryland Dental School, Baltimore, MD 21201-1586, USA. rnd001@dental.umaryland.edu
Abstract:
Descending modulation of nociception is enhanced following tissue injury. These changes include suppression and facilitation of nocifensive behavior and spinal dorsal horn hyperexcitability originating at brain stem sites. Evidence has been presented that such descending modulation undergoes time-dependent changes following persistent inflammation. There is an initial decrease and a subsequent increase in the excitability of neurons in the RVM involving facilitation and inhibition. The enhanced descending modulation includes changes in the activation and gene expression of the NMDA and AMPA excitatory amino acid receptors. In vivo electrophysiological recordings further reveal a change in the response profile of RVM neurons during the development of inflammation: cells previously unresponsive to nociceptive stimuli, exhibit response profiles characteristic of pain-modulating neurons. These findings demonstrate activity-dependent plasticity in brain stem circuits that includes changes in excitatory amino acid receptor activation and sensitivity and a phenotypic switch of some RVM neurons.
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