Journal article
Gi-Protein Coupled 5-HT1B/D Receptor Agonist Sumatriptan Induces Type I Hyperalgesic Priming
Pain (Amsterdam), Vol.157(8), pp.1773-1782
08/01/2016
DOI: 10.1097/j.pain.0000000000000581
PMID: 27075428
Abstract
We have recently described a novel form of hyperalgesic priming (type II) induced by agonists at two clinically important Gi-protein coupled receptors (Gi-GPCRs), mu-opioid and A1-adenosine. Like mu-opioids, the anti-migraine triptans, which act at 5-HT1B/D Gi-GPCRs have been implicated in pain chronification. We determined if sumatriptan, a prototypical 5-HT1B/D agonist produces type II priming. Characteristic of hyperalgesic priming, intradermal injection of sumatriptan (10 ng) induced a change in nociceptor function such that a subsequent injection of prostaglandin-E2 (PGE2) induces prolonged mechanical hyperalgesia. However, onset to priming was delayed 3 days, characteristic of type I priming. Also characteristic of type I priming, a protein kinase Cε (PKCε), but not a PKA inhibitor attenuated the prolongation phase of PGE2 hyperalgesia. The prolongation of PGE2 hyperalgesia was also permanently reversed by intradermal injection of cordycepin, a protein translation inhibitor. Also, hyperalgesic priming did not occur in animals pre-treated with pertussis toxin or IB4-positive nociceptor toxin, IB4-saporin. Finally, as observed for other agonists that induce type I priming, sumatriptan did not induce priming in female rats. The prolongation of PGE2 hyperalgesia induced by sumatriptan was partially prevented by co-injection of antagonists for the 5-HT1B and 5-HT1D, but not 5-HT7, serotonin receptors, and completely prevented by co-administration of a combination of the 5-HT1B and 5-HT1D antagonists. Moreover, the injection of selective agonists, for 5-HT1B and 5-HT1D receptors, also induced hyperalgesic priming. Our results suggest that sumatriptan, which signals via Gi-GPCRs, induces type I hyperalgesic priming, unlike agonists at other Gi-GPCRs, which induce type II priming.
Details
- Title: Subtitle
- Gi-Protein Coupled 5-HT1B/D Receptor Agonist Sumatriptan Induces Type I Hyperalgesic Priming
- Creators
- Dioneia Araldi - University of California, San FranciscoLuiz F. Ferrari - University of California, San FranciscoJon D. Levine - University of California, San Francisco
- Resource Type
- Journal article
- Publication Details
- Pain (Amsterdam), Vol.157(8), pp.1773-1782
- DOI
- 10.1097/j.pain.0000000000000581
- PMID
- 27075428
- ISSN
- 0304-3959
- eISSN
- 1872-6623
- Number of pages
- 10
- Language
- English
- Date published
- 08/01/2016
- Academic Unit
- Neuroscience and Pharmacology
- Record Identifier
- 9985177944502771
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