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Continuous infusion of the cannabinoid WIN 55,212-2 to the site of a peripheral nerve injury reduces mechanical and cold hypersensitivity.
Br J Pharmacol 2007; 151(2):292-302BJ

Abstract

BACKGROUND AND PURPOSE

Cannabinoids have analgesic and anti-inflammatory properties but their use is limited by psychotropic activity at CNS receptors. Restricting cannabinoid delivery to peripheral tissues at systemically inactive doses offers a potential solution to this problem.

EXPERIMENTAL APPROACH

WIN 55,212-2 was continuously delivered to the site of a partial ligation injury to the sciatic nerve via a perineural catheter connected to a mini-osmotic 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.

KEY RESULTS

Compared with vehicle treatment, WIN 55,212-2 (1.4 microg microl(-1) hr(-1)) reduced hypersensitivity to stimuli applied to the injured limb at 2, 4 and 6 days after injury. The effects of WIN 55,212-2 (0.6-2.8 microg microl(-1) hr(-1)) were dose-dependent. Estimated EC(50) values for reduction in mean responses to mechanical and cooling stimulation (day 4 post-surgery) were 1.55 (95% C.I, [1.11-2.16]) microg microl(-1) hr(-1) and 1.52 (95% C.I, [1.07-2.18]) microg microl(-1) hr(-1), respectively. When delivered to the contralateral side to injury, WIN 55,212-2 (1.4 or 2.8 microg microl(-1) hr(-1)) did not significantly affect nerve injury-associated hypersensitivity. Co-perineural application of a CB(1) receptor antagonist SR141716a and WIN 55,212-2 prevented the effects of WIN 55,212-2 on hypersensitivity. Co-application of CB(2) receptor antagonist SR144528 reversed WIN 55,212-2's effect on mechanical hypersensitivity on day 2 only.

CONCLUSIONS AND IMPLICATIONS

These data support a peripheral antihyperalgesic effect of WIN 55,212-2 when delivered directly to the site of a nerve injury at systemically inactive doses.

Authors+Show Affiliations

Department of Anaesthetics, Intensive Care and Pain Medicine, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital Campus, London, UK.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17375083

Citation

Lever, I J., et al. "Continuous Infusion of the Cannabinoid WIN 55,212-2 to the Site of a Peripheral Nerve Injury Reduces Mechanical and Cold Hypersensitivity." British Journal of Pharmacology, vol. 151, no. 2, 2007, pp. 292-302.
Lever IJ, Pheby TM, Rice AS. Continuous infusion of the cannabinoid WIN 55,212-2 to the site of a peripheral nerve injury reduces mechanical and cold hypersensitivity. Br J Pharmacol. 2007;151(2):292-302.
Lever, I. J., Pheby, T. M., & Rice, A. S. (2007). Continuous infusion of the cannabinoid WIN 55,212-2 to the site of a peripheral nerve injury reduces mechanical and cold hypersensitivity. British Journal of Pharmacology, 151(2), pp. 292-302.
Lever IJ, Pheby TM, Rice AS. Continuous Infusion of the Cannabinoid WIN 55,212-2 to the Site of a Peripheral Nerve Injury Reduces Mechanical and Cold Hypersensitivity. Br J Pharmacol. 2007;151(2):292-302. PubMed PMID: 17375083.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Continuous infusion of the cannabinoid WIN 55,212-2 to the site of a peripheral nerve injury reduces mechanical and cold hypersensitivity. AU - Lever,I J, AU - Pheby,T M, AU - Rice,A S C, Y1 - 2007/03/20/ PY - 2007/3/22/pubmed PY - 2007/8/8/medline PY - 2007/3/22/entrez SP - 292 EP - 302 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 151 IS - 2 N2 - BACKGROUND AND PURPOSE: Cannabinoids have analgesic and anti-inflammatory properties but their use is limited by psychotropic activity at CNS receptors. Restricting cannabinoid delivery to peripheral tissues at systemically inactive doses offers a potential solution to this problem. EXPERIMENTAL APPROACH: WIN 55,212-2 was continuously delivered to the site of a partial ligation injury to the sciatic nerve via a perineural catheter connected to a mini-osmotic 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. KEY RESULTS: Compared with vehicle treatment, WIN 55,212-2 (1.4 microg microl(-1) hr(-1)) reduced hypersensitivity to stimuli applied to the injured limb at 2, 4 and 6 days after injury. The effects of WIN 55,212-2 (0.6-2.8 microg microl(-1) hr(-1)) were dose-dependent. Estimated EC(50) values for reduction in mean responses to mechanical and cooling stimulation (day 4 post-surgery) were 1.55 (95% C.I, [1.11-2.16]) microg microl(-1) hr(-1) and 1.52 (95% C.I, [1.07-2.18]) microg microl(-1) hr(-1), respectively. When delivered to the contralateral side to injury, WIN 55,212-2 (1.4 or 2.8 microg microl(-1) hr(-1)) did not significantly affect nerve injury-associated hypersensitivity. Co-perineural application of a CB(1) receptor antagonist SR141716a and WIN 55,212-2 prevented the effects of WIN 55,212-2 on hypersensitivity. Co-application of CB(2) receptor antagonist SR144528 reversed WIN 55,212-2's effect on mechanical hypersensitivity on day 2 only. CONCLUSIONS AND IMPLICATIONS: These data support a peripheral antihyperalgesic effect of WIN 55,212-2 when delivered directly to the site of a nerve injury at systemically inactive doses. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/17375083/Continuous_infusion_of_the_cannabinoid_WIN_55212_2_to_the_site_of_a_peripheral_nerve_injury_reduces_mechanical_and_cold_hypersensitivity_ L2 - https://doi.org/10.1038/sj.bjp.0707210 DB - PRIME DP - Unbound Medicine ER -