Cannabinoid modulation of cutaneous Aδ nociceptors during inflammation

Carl Potenzieri, Thaddeus S. Brink, Cholawat Pacharinsak, Donald A Simone

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Previous studies have demonstrated that locally administered cannabinoids attenuate allodynia and hyperalgesia through activation of peripheral cannabinoid receptors (CB1 and CB2). However, it is currently unknown if cannabinoids alter the response properties of nociceptors. In the present study, correlative behavioral and in vivo electrophysiological studies were conducted to determine if peripheral administration of the cannabinoid receptor agonists arachidonyl-2′-chloroethylamide (ACEA) or (R)-(+)-methanandamide (methAEA) could attenuate mechanical allodynia and hyperalgesia, and decrease mechanically evoked responses of Aδ nociceptors. Twenty-four hours after intraplantar injection of complete Freund's adjuvant (CFA), rats exhibited allodynia (decrease in paw withdrawal threshold) and hyperalgesia (increase in paw withdrawal frequency), which were attenuated by both ACEA and methAEA. The antinociceptive effects of these cannabinoids were blocked by co-administration with the CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophen yl)-4-methyl-1H- pyrazole-3-carboxamide (AM251) but not with the CB2 receptor antagonist 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-y l](4-methoxyphenyl)methanone (AM630). ACEA and methAEA did not produce antinociception under control, non-inflamed conditions 24 h after intraplantar injection of saline. In parallel studies, recordings were made from cutaneous Aδ nociceptors from inflamed or control, non-inflamed skin. Both ACEA and methAEA decreased responses evoked by mechanical stimulation of Aδ nociceptors from inflamed skin but not from non-inflamed skin, and this decrease was blocked by administration of the CB1 receptor antagonist AM251. These results suggest that attenuation of mechanically evoked responses of Aδ nociceptors contributes to the behavioral antinociception produced by activation of peripheral CB1 receptors during inflammation.

Original languageEnglish (US)
Pages (from-to)2794-2806
Number of pages13
JournalJournal of neurophysiology
Volume100
Issue number5
DOIs
StatePublished - Nov 1 2008

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Nociceptors
Cannabinoids
Hyperalgesia
Cannabinoid Receptor CB1
Inflammation
Skin
Cannabinoid Receptor CB2
Dichlorophen
Cannabinoid Receptor Agonists
Injections
Freund's Adjuvant
arachidonyl-2-chloroethylamide

Cite this

Cannabinoid modulation of cutaneous Aδ nociceptors during inflammation. / Potenzieri, Carl; Brink, Thaddeus S.; Pacharinsak, Cholawat; Simone, Donald A.

In: Journal of neurophysiology, Vol. 100, No. 5, 01.11.2008, p. 2794-2806.

Research output: Contribution to journalArticle

Potenzieri, Carl ; Brink, Thaddeus S. ; Pacharinsak, Cholawat ; Simone, Donald A. / Cannabinoid modulation of cutaneous Aδ nociceptors during inflammation. In: Journal of neurophysiology. 2008 ; Vol. 100, No. 5. pp. 2794-2806.
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