Periaqueductal grey EP3 receptors facilitate spinal nociception in arthritic secondary hypersensitivity

Drake, Robert A.R.; Leith, J.L.; Almahasneh, F.; Martindale, J.; Wilson, A.W.; Lumb, B.M.; Donaldson, Lucy F.

Abstract

Descending controls on spinal nociceptive processing play a pivotal role in shaping the pain experience following tissue injury. Secondary hypersensitivity develops within undamaged tissue adjacent, and distant to, damaged sites. Spinal neuronal pools innervating regions of secondary hypersensitivity are dominated by descending facilitation that amplifies spinal inputs from un-sensitized peripheral nociceptors. Cyclooxygenase–prostaglandin E2 signaling within the ventrolateral periaqueductal grey (vlPAG) is pro-nociceptive in naïve and acutely inflamed animals but its contributions in more prolonged inflammation and, importantly, secondary hypersensitivity remain unknown. In naïve rats, prostaglandin EP3 receptor (EP3R) antagonism in vlPAG modulated noxious withdrawal reflex (EMG) thresholds to preferential C-, but not A-, nociceptor activation, and raised thermal withdrawal thresholds in awake animals. In rats with inflammatory arthritis, secondary mechanical and thermal hypersensitivity of the hind-paw developed, and this was associated with spinal sensitization to Anociceptor inputs alone. In arthritic rats, blockade of vlPAG EP3R raised EMG thresholds to C-nociceptor activation in the area of secondary hypersensitivity to a degree equivalent to that evoked by the same manipulation in naïve rats.

Citation

Drake, R. A., Leith, J., Almahasneh, F., Martindale, J., Wilson, A., Lumb, B., & Donaldson, L. F. (2016). Periaqueductal grey EP3 receptors facilitate spinal nociception in arthritic secondary hypersensitivity. Journal of Neuroscience, 36(35), https://doi.org/10.1523/JNEUROSCI.4393-15.2016

• Journal Article Type: Article
• Acceptance Date: Jun 22, 2016
• Publication Date: Aug 31, 2016
• Deposit Date: Jul 7, 2016
• Publicly Available Date: Aug 31, 2016
• Journal: Journal of Neuroscience
• Electronic ISSN: 1529-2401
• Publisher: Society for Neuroscience
• Peer Reviewed: Peer Reviewed
• Volume: 36
• Issue: 35
• DOI: https://doi.org/10.1523/JNEUROSCI.4393-15.2016
• Keywords: Arthritis, Descending Facilitation, Inflammation, Periaqueductal grey, Prostaglandins, Secondary Hyperalgesia
• Public URL: https://nottingham-repository.worktribe.com/output/803615
• Publisher URL: http://www.jneurosci.org/content/36/35/9026
• Contract Date: Jul 7, 2016