Periaqueductal grey EP3 receptors facilitate spinal nociception in arthritic secondary hypersensitivity
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 hypersensitivit...
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Society for Neuroscience
2016
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| Online Access: | https://eprints.nottingham.ac.uk/34730/ |
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| author | Drake, Robert A.R. Leith, J.L. Almahasneh, F. Martindale, J. Wilson, A.W. Lumb, B.M. Donaldson, Lucy F. |
| author_facet | Drake, Robert A.R. Leith, J.L. Almahasneh, F. Martindale, J. Wilson, A.W. Lumb, B.M. Donaldson, Lucy F. |
| author_sort | Drake, Robert A.R. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:23:54Z |
| format | Article |
| id | nottingham-34730 |
| institution | University of Nottingham Malaysia Campus |
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| last_indexed | 2025-11-14T19:23:54Z |
| publishDate | 2016 |
| publisher | Society for Neuroscience |
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| spelling | nottingham-347302020-05-04T18:05:01Z https://eprints.nottingham.ac.uk/34730/ 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. 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. Society for Neuroscience 2016-08-31 Article PeerReviewed Drake, Robert A.R., Leith, J.L., Almahasneh, F., Martindale, J., Wilson, A.W., Lumb, B.M. and Donaldson, Lucy F. (2016) Periaqueductal grey EP3 receptors facilitate spinal nociception in arthritic secondary hypersensitivity. Journal of Neuroscience, 36 (35). pp. 9026-9040. ISSN 1529-2401 Arthritis Descending Facilitation Inflammation Periaqueductal grey Prostaglandins Secondary Hyperalgesia http://www.jneurosci.org/content/36/35/9026 doi:10.1523/JNEUROSCI.4393-15.2016 doi:10.1523/JNEUROSCI.4393-15.2016 |
| spellingShingle | Arthritis Descending Facilitation Inflammation Periaqueductal grey Prostaglandins Secondary Hyperalgesia Drake, Robert A.R. Leith, J.L. Almahasneh, F. Martindale, J. Wilson, A.W. Lumb, B.M. Donaldson, Lucy F. Periaqueductal grey EP3 receptors facilitate spinal nociception in arthritic secondary hypersensitivity |
| title | Periaqueductal grey EP3 receptors facilitate spinal nociception in arthritic secondary hypersensitivity |
| title_full | Periaqueductal grey EP3 receptors facilitate spinal nociception in arthritic secondary hypersensitivity |
| title_fullStr | Periaqueductal grey EP3 receptors facilitate spinal nociception in arthritic secondary hypersensitivity |
| title_full_unstemmed | Periaqueductal grey EP3 receptors facilitate spinal nociception in arthritic secondary hypersensitivity |
| title_short | Periaqueductal grey EP3 receptors facilitate spinal nociception in arthritic secondary hypersensitivity |
| title_sort | periaqueductal grey ep3 receptors facilitate spinal nociception in arthritic secondary hypersensitivity |
| topic | Arthritis Descending Facilitation Inflammation Periaqueductal grey Prostaglandins Secondary Hyperalgesia |
| url | https://eprints.nottingham.ac.uk/34730/ https://eprints.nottingham.ac.uk/34730/ https://eprints.nottingham.ac.uk/34730/ |