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The importance of genetic background on pain behaviours and pharmacological sensitivity in the rat spared serve injury model of peripheral neuropathic pain.
Eur J Pharmacol. 2007 Jun 14; 564(1-3):103-11.EJ

Abstract

Neuropathic pain conditions can encompass a diverse constellation of signs and symptoms consisting of sensory deficits, allodynia and hyperalgesia. Animal models of neuropathic pain have enabled the identification of key pathophysiological changes occurring within nociceptive pathways as a result of injury, and serve an invaluable role for preclinical screening of novel analgesic candidates. We have produced the first systematic description of the development and maintenance, and the pharmacological sensitivity of nociceptive behaviours in four rat strains with different genetic background (outbred Sprague-Dawley and inbred Brown Norway, Lewis and Fischer 344 rats), using the spared nerve injury model of peripheral neuropathic pain. Hindpaw mechanical hypersensitivity was evident from 7 to 30 days post-injury in all four strains, developing most quickly and severely in Fischer 344 rats; Lewis rats were least affected. Morphine (6 but not 3 mg/kg, s.c.) and gabapentin (100 but not 50 mg/kg, s.c.) had significant antiallodynic and antihyperalgesic actions in all four strains after spared nerve injury, although marked differences in potency across strains were observed. Two strains (Fischer 344 rats and Lewis) were insensitive to the antihyperalgesic properties of gaboxadol (15 mg/kg) whereas gaboxadol (6 mg/kg) was equipotent to morphine (6 mg/kg) in two other strains (Sprague-Dawley and Brown Norway). The observed pharmacogenetic variations have important implications for the preclinical testing of drugs, and provide a basis for development of pharmacogenomics in neuropathic pain.

Authors+Show Affiliations

Department of Pharmacology, Danish University of Pharmaceutical Sciences, Jagtvej 120, Copenhagen, Denmark. Frederikrode@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17383631

Citation

Rode, Frederik, et al. "The Importance of Genetic Background On Pain Behaviours and Pharmacological Sensitivity in the Rat Spared Serve Injury Model of Peripheral Neuropathic Pain." European Journal of Pharmacology, vol. 564, no. 1-3, 2007, pp. 103-11.
Rode F, Thomsen M, Broløs T, et al. The importance of genetic background on pain behaviours and pharmacological sensitivity in the rat spared serve injury model of peripheral neuropathic pain. Eur J Pharmacol. 2007;564(1-3):103-11.
Rode, F., Thomsen, M., Broløs, T., Jensen, D. G., Blackburn-Munro, G., & Bjerrum, O. J. (2007). The importance of genetic background on pain behaviours and pharmacological sensitivity in the rat spared serve injury model of peripheral neuropathic pain. European Journal of Pharmacology, 564(1-3), 103-11.
Rode F, et al. The Importance of Genetic Background On Pain Behaviours and Pharmacological Sensitivity in the Rat Spared Serve Injury Model of Peripheral Neuropathic Pain. Eur J Pharmacol. 2007 Jun 14;564(1-3):103-11. PubMed PMID: 17383631.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The importance of genetic background on pain behaviours and pharmacological sensitivity in the rat spared serve injury model of peripheral neuropathic pain. AU - Rode,Frederik, AU - Thomsen,Mads, AU - Broløs,Tine, AU - Jensen,Dorthe G, AU - Blackburn-Munro,Gordon, AU - Bjerrum,Ole J, Y1 - 2007/02/17/ PY - 2006/05/08/received PY - 2007/02/05/revised PY - 2007/02/06/accepted PY - 2007/3/27/pubmed PY - 2007/8/19/medline PY - 2007/3/27/entrez SP - 103 EP - 11 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 564 IS - 1-3 N2 - Neuropathic pain conditions can encompass a diverse constellation of signs and symptoms consisting of sensory deficits, allodynia and hyperalgesia. Animal models of neuropathic pain have enabled the identification of key pathophysiological changes occurring within nociceptive pathways as a result of injury, and serve an invaluable role for preclinical screening of novel analgesic candidates. We have produced the first systematic description of the development and maintenance, and the pharmacological sensitivity of nociceptive behaviours in four rat strains with different genetic background (outbred Sprague-Dawley and inbred Brown Norway, Lewis and Fischer 344 rats), using the spared nerve injury model of peripheral neuropathic pain. Hindpaw mechanical hypersensitivity was evident from 7 to 30 days post-injury in all four strains, developing most quickly and severely in Fischer 344 rats; Lewis rats were least affected. Morphine (6 but not 3 mg/kg, s.c.) and gabapentin (100 but not 50 mg/kg, s.c.) had significant antiallodynic and antihyperalgesic actions in all four strains after spared nerve injury, although marked differences in potency across strains were observed. Two strains (Fischer 344 rats and Lewis) were insensitive to the antihyperalgesic properties of gaboxadol (15 mg/kg) whereas gaboxadol (6 mg/kg) was equipotent to morphine (6 mg/kg) in two other strains (Sprague-Dawley and Brown Norway). The observed pharmacogenetic variations have important implications for the preclinical testing of drugs, and provide a basis for development of pharmacogenomics in neuropathic pain. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17383631/The_importance_of_genetic_background_on_pain_behaviours_and_pharmacological_sensitivity_in_the_rat_spared_serve_injury_model_of_peripheral_neuropathic_pain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00194-X DB - PRIME DP - Unbound Medicine ER -