Loss of cortical control over the descending pain modulatory system determines the development of the neuropathic pain state in rats

Robert A R Drake*, Bridget M Lumb, R Apps, Anthony E Pickering

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

17 Citations (Scopus)
170 Downloads (Pure)

Abstract

The loss of descending inhibitory control is thought critical to the development of chronic pain but what causes this loss in function is not well understood. We have investigated the dynamic contribution of prelimbic cortical neuronal projections to the periaqueductal grey (PrL-P) to the development of neuropathic pain in rats using combined opto- and chemogenetic approaches. We found PrL-P neurons to exert a tonic inhibitory control on thermal withdrawal thresholds in uninjured animals. Following nerve injury, ongoing activity in PrL-P neurons masked latent hypersensitivity and improved affective state. However, this function is lost as the development of sensory hypersensitivity emerges. Despite this loss of tonic control, opto-activation of PrL-P neurons at late post-injury timepoints could restore the anti-allodynic effects by inhibition of spinal nociceptive processing. We suggest that the loss of cortical drive to the descending pain modulatory system underpins the expression of neuropathic sensitisation after nerve injury.
Original languageEnglish
Article numbere65156
Pages (from-to)1-22
Number of pages22
JournaleLife
Volume10
DOIs
Publication statusPublished - 8 Feb 2021

Bibliographical note

Funding Information:
We would like to thank Mrs Rachel Bissett for her assistance with histological processing and the Wolfson Bioimaging Facility for their support and assistance with image acquisition. We would like to thank Dr Eric J Kremer for his kind gift of CAV-CMV-CRE, and Dr Brian Roth and Dr Karl Deisseroth for the supply of viral vectors used in this work. This work was supported by the Medical Research Council Grant number MR/P00668/X1.

Publisher Copyright:
© Drake et al.

Structured keywords

  • Brain and Behaviour
  • prefrontal cortex
  • periaqueductal grey
  • brain networks
  • Physical and Mental Health
  • peripheral injury
  • pain
  • nociception
  • Anaesthesia Pain and Critical Care

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