Loss of cortical control over the descending pain modulatory system determines the development of the neuropathic pain state in rats
- University of Bristol, United Kingdom
- University of Cardiff, United Kingdom
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 chemo-genetic 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.
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All data generated or analysed are included in the manuscript
Article and author information
Author details
Anthony E Pickering
Funding
Medical Research Council (MR/P00668/X1)
- Robert A R Drake
- Richard Apps
- Bridget M Lumb
- Anthony E Pickering
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental and surgical procedures were conducted in accordance with the UK Animals (Scientific Procedures) Act (1998) and local Animal Welfare and Ethical Review Body (AWERB).
Copyright
© 2021, Drake et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Loss of cortical control over the descending pain modulatory system determines the development of the neuropathic pain state in rats
eLife 10:e65156.
https://doi.org/10.7554/eLife.65156
