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Comparison of antinociceptive actions of standard analgesics in attenuating capsaicin and nerve-injury-induced mechanical hypersensitivity.
Neuroscience. 2006 Dec 01; 143(2):587-96.N

Abstract

Intradermal capsaicin injection produces immediate spontaneous pain behaviors, and a secondary mechanical hypersensitivity (SMH) that is employed in the clinic as a model potentially predictive of human neuropathic pain. Presently, we have characterized capsaicin-induced SMH in rats, and compared pharmacological actions of standard analgesics in this and two nerve injury models, the L5/L6 spinal nerve ligation (SNL) and sciatic nerve chronic constriction injury (CCI) models. Intraplantar capsaicin produced dose-related SMH (enhanced paw withdrawal response to von Frey monofilament stimulation at an area away from injection site) that lasted for over 4 h. While pretreatment with a potent selective transient receptor potential vanilloid receptor-1 (TRPV1) antagonist A-425619 (1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea) prevented development of acute nocifensive (flinching) behavior immediately following capsaicin injection (ED(50)=4.9 mg/kg), the compound failed to attenuate the SMH when administered 2 h following capsaicin (10 microg/10 microl). Additional standard analgesics were also tested 3 h following intraplantar capsaicin in the SMH model. Comparison of their potencies in attenuating mechanical hypersensitivity in capsaicin, SNL and CCI models revealed similar ED(50)s for morphine (2.3 mg/kg, 1.6 mg/kg and 3.2 mg/kg, respectively), gabapentin (33.1 mg/kg, 33.9 mg/kg and 26.3 mg/kg, respectively) and lamotrigine (9.1 mg/kg, 8.9 mg/kg and 15.5 mg/kg, respectively). Duloxetine produced 50-65% effect at the highest tested dose (50 mg/kg), whereas the highest tested doses of morphine (10 mg/kg), gabapentin (85.5 mg/kg) and lamotrigine (30 mg/kg) all produced >70% efficacy in capsaicin SMH, SNL and CCI models. In contrast, celecoxib and ibuprofen showed weak effects in all three models. All standard analgesics generally had weak efficacy in attenuating capsaicin-induced immediate acute flinching behavior when administered before capsaicin. These results provide further support to the suggestions that distinct pharmacological mechanisms underlie capsaicin-induced acute nocifensive and SMH behaviors, and certain neuronal mechanisms underlying neuropathic pain states are also contributory to capsaicin-induced SMH.

Authors+Show Affiliations

Abbott Laboratories, Neuroscience Research, GPRD R4N5 100 Abbott Park Road, Abbott Park, IL 60064, USA. shailen.joshi@abbott.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16962719

Citation

Joshi, S K., et al. "Comparison of Antinociceptive Actions of Standard Analgesics in Attenuating Capsaicin and Nerve-injury-induced Mechanical Hypersensitivity." Neuroscience, vol. 143, no. 2, 2006, pp. 587-96.
Joshi SK, Hernandez G, Mikusa JP, et al. Comparison of antinociceptive actions of standard analgesics in attenuating capsaicin and nerve-injury-induced mechanical hypersensitivity. Neuroscience. 2006;143(2):587-96.
Joshi, S. K., Hernandez, G., Mikusa, J. P., Zhu, C. Z., Zhong, C., Salyers, A., Wismer, C. T., Chandran, P., Decker, M. W., & Honore, P. (2006). Comparison of antinociceptive actions of standard analgesics in attenuating capsaicin and nerve-injury-induced mechanical hypersensitivity. Neuroscience, 143(2), 587-96.
Joshi SK, et al. Comparison of Antinociceptive Actions of Standard Analgesics in Attenuating Capsaicin and Nerve-injury-induced Mechanical Hypersensitivity. Neuroscience. 2006 Dec 1;143(2):587-96. PubMed PMID: 16962719.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of antinociceptive actions of standard analgesics in attenuating capsaicin and nerve-injury-induced mechanical hypersensitivity. AU - Joshi,S K, AU - Hernandez,G, AU - Mikusa,J P, AU - Zhu,C Z, AU - Zhong,C, AU - Salyers,A, AU - Wismer,C T, AU - Chandran,P, AU - Decker,M W, AU - Honore,P, Y1 - 2006/09/08/ PY - 2006/03/29/received PY - 2006/07/06/revised PY - 2006/08/01/accepted PY - 2006/9/12/pubmed PY - 2007/1/27/medline PY - 2006/9/12/entrez SP - 587 EP - 96 JF - Neuroscience JO - Neuroscience VL - 143 IS - 2 N2 - Intradermal capsaicin injection produces immediate spontaneous pain behaviors, and a secondary mechanical hypersensitivity (SMH) that is employed in the clinic as a model potentially predictive of human neuropathic pain. Presently, we have characterized capsaicin-induced SMH in rats, and compared pharmacological actions of standard analgesics in this and two nerve injury models, the L5/L6 spinal nerve ligation (SNL) and sciatic nerve chronic constriction injury (CCI) models. Intraplantar capsaicin produced dose-related SMH (enhanced paw withdrawal response to von Frey monofilament stimulation at an area away from injection site) that lasted for over 4 h. While pretreatment with a potent selective transient receptor potential vanilloid receptor-1 (TRPV1) antagonist A-425619 (1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea) prevented development of acute nocifensive (flinching) behavior immediately following capsaicin injection (ED(50)=4.9 mg/kg), the compound failed to attenuate the SMH when administered 2 h following capsaicin (10 microg/10 microl). Additional standard analgesics were also tested 3 h following intraplantar capsaicin in the SMH model. Comparison of their potencies in attenuating mechanical hypersensitivity in capsaicin, SNL and CCI models revealed similar ED(50)s for morphine (2.3 mg/kg, 1.6 mg/kg and 3.2 mg/kg, respectively), gabapentin (33.1 mg/kg, 33.9 mg/kg and 26.3 mg/kg, respectively) and lamotrigine (9.1 mg/kg, 8.9 mg/kg and 15.5 mg/kg, respectively). Duloxetine produced 50-65% effect at the highest tested dose (50 mg/kg), whereas the highest tested doses of morphine (10 mg/kg), gabapentin (85.5 mg/kg) and lamotrigine (30 mg/kg) all produced >70% efficacy in capsaicin SMH, SNL and CCI models. In contrast, celecoxib and ibuprofen showed weak effects in all three models. All standard analgesics generally had weak efficacy in attenuating capsaicin-induced immediate acute flinching behavior when administered before capsaicin. These results provide further support to the suggestions that distinct pharmacological mechanisms underlie capsaicin-induced acute nocifensive and SMH behaviors, and certain neuronal mechanisms underlying neuropathic pain states are also contributory to capsaicin-induced SMH. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/16962719/Comparison_of_antinociceptive_actions_of_standard_analgesics_in_attenuating_capsaicin_and_nerve_injury_induced_mechanical_hypersensitivity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(06)01074-8 DB - PRIME DP - Unbound Medicine ER -