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The role of central and peripheral Cannabinoid 1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain. (Novartic Institute for Medical Sciences, London, United Kingdom) Pain. 2001;92:91–100.
Author(s) -
Fox Alyson,
Kesingland Adam,
Gentry Clive,
McNair Kara,
Patel Sadhana,
Urban Laszlo,
James Iain
Publication year - 2001
Publication title -
pain practice
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 58
eISSN - 1533-2500
pISSN - 1530-7085
DOI - 10.1046/j.1533-2500.2001.1039_18.x
Subject(s) - rimonabant , medicine , cannabinoid , hyperalgesia , neuropathic pain , pharmacology , catalepsy , cannabinoid receptor , antagonist , anesthesia , allodynia , cannabinoid receptor antagonist , nociception , receptor , dopamine , haloperidol
This study examined the effects of cannabinoid agonists on hyperalgesia in a model of neuropathic pain in the rat and investigated the possible sites of action. The antihyperalgesic activity of the cannabinoids was compared with their ability to elicit behavioral effects characteristic of central cannabinoid activity. WIN55, 212‐2 (0.3–10 mg/kg −1 ), CP‐55, 940 (0.03–1 mg/kg −1 ), and HU‐210 (0.001–0.03 mg/kg −1 ) were all active in a “tetrad” of tests consisting of tail‐flick, catalepsy, rotarod, and hypothermia following subcutaneous administration, with a rank order of potency in each of HU‐210> CP‐55, 940> WIN55, 212‐2. The effects of WIN55, 212‐2 in each assay were blocked by the Cannabinoid 1 (CB 1 ) antagonist SR141716A. In the partial sciatic ligation model if neuropathic pain WIN55, 212‐2, CP‐55, 940, and HU‐210 produced complete reversal of mechanical hyperalgesia within 3 hours of subcutaneous administration with D 50 values of 0.52, 0.08, and 0.005 mg/kg −1 , respectively. In this model WIN55, 212‐2 was also effective against thermal hyperalgesia and mechanical allodynia. WIN55, 212‐2 produced pronounced reversal of mechanical hyperalgesia following intrathecal administration that was blocked by the CB 1 antagonist SR141716A. Following intraplantar administration into the ipsilateral hindpaw, WIN55, 212‐2 produced up to 70% reversal of mechanical hyperalgesia, although activity was also observed at high doses following injection into contralateral paw. The antihyperalgesic effect of WIN55, 212‐2 injected into the ipsilateral paw was blocked by subcutaneously administered SR141716A, but was not affected by intrathecally administered SR141716A. Conclude that cannabinoids are highly potent and efficacious antihyperalgesic agents in a model of neuropathic pain. This activity is likely to be mediated via action in both the CNS and in the periphery. Comment by Leland Lou, M.D. Rat study that looked at the potential of cannabinoids in the management of neuropathic pain. The data seem to indicate the presence of peripheral cannabinoid receptors for suppression of neuropathic pain. Historically, a central mechanism of action for cannabinoid's analgesic and antihyperalgesic properties is thought to be responsible. Unfortunately, this report only confirms previous studies finding a peripheral mechanism of action.