Pharmacological evaluation of the selective spinal nerve ligation model of neuropathic pain in the rat.
Rodent models of neuropathic pain are used to investigate the underlying mechanisms of pain associated with damage to peripheral nerves and to evaluate the efficacy of novel compounds. However, few models have been adequately characterized and the validity of many models remains unclear. The present experiment examined the activity of known anti-allodynic compounds in the L5 spinal nerve ligation (SNL) model of peripheral mononeuropathy in the rat, a modified version of the L5/L6 SNL model [S.H. Kim, J.M. Chung, An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat, Pain 50 (1992) 355-363]. Tactile sensitivity was measured 7-21 days post-surgery using von Frey monofilaments before and following treatment with gabapentin (30, 60 and 120 mg/kg), morphine (1, 3 and 6 mg/kg), amitriptyline (1.5, 3 and 10 mg/kg), fluoxetine (3, 10 and 30 mg/kg), WIN55,212-2 (0.5, 1 and 2.5 mg/kg), indomethacin (1 and 5 mg/kg) or U-50,488H (3 and 6 mg/kg). Compared to sham-operated control animals, L5 SNL animals displayed significant tactile allodynia in the ipsilateral hindpaw that was completely reversed by treatment with gabapentin, morphine, and WIN55,212-2, partially reversed by amitriptyline and fluoxetine, and unaffected by U-50,488H or indomethacin. The robust effects of the non-selective cannabinoid receptor agonist WIN55,212-2 and morphine support reports in the literature that systemic cannabinoid receptor agonists and opioids are active in neuropathic pain. These results suggest that the L5 SNL model can be utilized to determine the anti-allodynic activity of novel compounds.
LaBuda
Christopher J
CJ
Department of Pharmacology, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA. clabuda@adolor.com
Little
Patrick J
PJ
D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D003714:Denervation; D004195:Disease Models, Animal; D008026:Ligation / Q000379:methods; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D019635:Neurosurgical Procedures / Q000379:methods*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid / Q000378:metabolism; D013127:Spinal Nerves / Q000293:injuries* / Q000503:physiopathology / Q000601:surgery*; D016896:Treatment Outcome
D000700:Analgesics; D000701:Analgesics, Opioid; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; D043882:Receptors, Cannabinoid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone