Abstract | OBJECTIVE:
Melittin is the main peptide in bee venom and causes both persistent spontaneous nociception and pain hypersensitivity. Our recent studies indicated that both transient receptor potential (TRP) vanilloid receptor 1 (TRPV1) and canonical TRPs (TRPCs) are involved in mediating the melittin-induced activation of different subpopulations of primary nociceptive cells. Here, we further determined whether TRPC channels are involved in melittin-induced inflammatory nociceptive responses in behavioral assays. METHODS: The anti-nociceptive and anti-hyperalgesic effects of localized peripheral administration of three doses of the non-selective TRPC antagonist, SKF-96365 (1-{β-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenyl}-1H- imidazole hydrochloride), were evaluated in melittin tests. Pain-related behaviors were rated by counting the number of paw flinches, and measuring paw withdrawal thermal latency (s) and paw withdrawl mechanical threshold (g), over a 1-h time-course. RESULTS: Localized peripheral SKF-96365 given before melittin prevented, and given after melittin significantly suppressed, the melittin-evoked persistent spontaneous nociception. Pre-blockade and post-suppression of activation of primary nociceptive activity resulted in decreased hypersensitivity to both thermal and mechanical stimuli applied to the primary injury site of the ipsilateral hindpaw, despite dose-effect differences between thermal and mechanical hyperalgesia. However, local administration of SKF-96365 into the contralateral hindpaw had no significant effect on any pain-associated behaviors. In addition, SKF-96365 had no effect on baseline threshold for either thermal or mechanical sensitivity under normal conditions. CONCLUSION:
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Authors | Jing Ding, Jia-Rui Zhang, Yan Wang, Chun-Li Li, Dan Lu, Su-Min Guan, Jun Chen |
Journal | Neuroscience bulletin
(Neurosci Bull)
Vol. 28
Issue 2
Pg. 173-81
(Apr 2012)
ISSN: 1995-8218 [Electronic] Singapore |
PMID | 22466128
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Calcium Channel Blockers
- Imidazoles
- Inflammation Mediators
- TRPC Cation Channels
- Melitten
- 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
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Topics |
- Animals
- Calcium Channel Blockers
(pharmacology)
- Chronic Pain
(chemically induced, drug therapy, pathology)
- Disease Models, Animal
- Ganglia, Spinal
(drug effects, pathology)
- Imidazoles
(pharmacology)
- Inflammation
(complications, drug therapy, pathology)
- Inflammation Mediators
(physiology)
- Male
- Melitten
(pharmacology)
- Nociceptors
(drug effects, pathology)
- Rats
- Rats, Sprague-Dawley
- TRPC Cation Channels
(antagonists & inhibitors, physiology)
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