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Restricting cannabinoid delivery to peripheral tissues at systemically inactive doses offers a potential solution to this problem.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>WIN 55,212\u20102 was continuously delivered to the site of a partial ligation injury to the sciatic nerve via a perineural catheter connected to a mini\u2010osmotic pump implanted at the time of injury. Bilateral reflex limb withdrawal behaviour was measured in adult male Wistar rats in response to mechanical and cooling stimulation of the hind paw.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>Compared with vehicle treatment, WIN 55,212\u20102 (1.4\u03bcg \u03bcl<jats:sup>\u22121<\/jats:sup> hr<jats:sup>\u22121<\/jats:sup>) reduced hypersensitivity to stimuli applied to the injured limb at 2, 4 and 6 days after injury. The effects of WIN 55,212\u20102 (0.6\u20102.8\u03bcg \u03bcl<jats:sup>\u22121<\/jats:sup> hr<jats:sup>\u22121<\/jats:sup>) were dose\u2010dependent. Estimated EC<jats:sub>50<\/jats:sub> values for reduction in mean responses to mechanical and cooling stimulation (day 4 post\u2010surgery) were 1.55 (95% C.I, [1.11\u20102.16]) \u03bcg \u03bcl<jats:sup>\u22121<\/jats:sup> hr<jats:sup>\u22121<\/jats:sup> and 1.52 (95% C.I, [1.07\u20102.18]) \u03bcg \u03bcl<jats:sup>\u22121<\/jats:sup> hr<jats:sup>\u22121<\/jats:sup>, respectively. When delivered to the contralateral side to injury, WIN 55,212\u20102 (1.4 or 2.8\u03bcg \u03bcl<jats:sup>\u22121<\/jats:sup> hr<jats:sup>\u22121<\/jats:sup>) did not significantly affect nerve injury\u2010associated hypersensitivity. Co\u2010perineural application of a CB<jats:sub>1<\/jats:sub> receptor antagonist SR141716a and WIN 55,212\u20102 prevented the effects of WIN 55,212\u20102 on hypersensitivity. Co\u2010application of CB<jats:sub>2<\/jats:sub> receptor antagonist SR144528 reversed WIN 55,212\u20102's effect on mechanical hypersensitivity on day 2 only.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>These data support a peripheral antihyperalgesic effect of WIN 55,212\u20102 when delivered directly to the site of a nerve injury at systemically inactive doses.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2007) <jats:bold>151<\/jats:bold>, 292\u2013302. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" 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