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Self-medication of a cannabinoid CB2 agonist in an animal model of neuropathic pain.
Pain 2011; 152(9):1976-87PAIN

Abstract

Drug self-administration methods were used to test the hypothesis that rats would self-medicate with a cannabinoid CB(2) agonist to attenuate a neuropathic pain state. Self-medication of the CB(2) agonist (R,S)-AM1241, but not vehicle, attenuated mechanical hypersensitivity produced by spared nerve injury. Switching rats from (R,S)-AM1241 to vehicle self-administration also decreased lever responding in an extinction paradigm. (R,S)-AM1241 self-administration did not alter paw withdrawal thresholds in sham-operated or naive animals. The percentage of active lever responding was similar in naive groups self-administering vehicle or (R,S)-AM1241. The CB(2) antagonist SR144528 blocked both antiallodynic effects of (R,S)-AM1241 self-medication and the percentage of active lever responding in neuropathic (but not naive) rats. Neuropathic and sham groups exhibited similar percentages of active lever responding for (R,S)-AM1241 on a fixed ratio 1 (FR1) schedule. However, neuropathic animals worked harder than shams to obtain (R,S)-AM1241 when the schedule of reinforcement was increased (to FR6). (R,S)-AM1241 self-medication on FR1, FR3, or FR6 schedules attenuated nerve injury-induced mechanical allodynia. (R,S)-AM1241 (900μg intravenously) failed to produce motor ataxia observed after administration of the mixed CB(1)/CB(2) agonist WIN55,212-2 (0.5mg/kg intravenously). Our results suggest that cannabinoid CB(2) agonists may be exploited to treat neuropathic pain with limited drug abuse liability and central nervous system side effects. These studies validate the use of drug self-administration methods for identifying nonpsychotropic analgesics possessing limited abuse potential. These methods offer potential to elucidate novel analgesics that suppress spontaneous neuropathic pain that is not measured by traditional assessments of evoked pain.

Authors+Show Affiliations

Neuroscience and Behavior Program, Department of Psychology, University of Georgia, Athens, GA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21550725

Citation

Gutierrez, Tannia, et al. "Self-medication of a Cannabinoid CB2 Agonist in an Animal Model of Neuropathic Pain." Pain, vol. 152, no. 9, 2011, pp. 1976-87.
Gutierrez T, Crystal JD, Zvonok AM, et al. Self-medication of a cannabinoid CB2 agonist in an animal model of neuropathic pain. Pain. 2011;152(9):1976-87.
Gutierrez, T., Crystal, J. D., Zvonok, A. M., Makriyannis, A., & Hohmann, A. G. (2011). Self-medication of a cannabinoid CB2 agonist in an animal model of neuropathic pain. Pain, 152(9), pp. 1976-87. doi:10.1016/j.pain.2011.03.038.
Gutierrez T, et al. Self-medication of a Cannabinoid CB2 Agonist in an Animal Model of Neuropathic Pain. Pain. 2011;152(9):1976-87. PubMed PMID: 21550725.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Self-medication of a cannabinoid CB2 agonist in an animal model of neuropathic pain. AU - Gutierrez,Tannia, AU - Crystal,Jonathon D, AU - Zvonok,Alexander M, AU - Makriyannis,Alexandros, AU - Hohmann,Andrea G, Y1 - 2011/05/08/ PY - 2011/01/04/received PY - 2011/03/15/revised PY - 2011/03/28/accepted PY - 2011/5/10/entrez PY - 2011/5/10/pubmed PY - 2012/6/5/medline SP - 1976 EP - 87 JF - Pain JO - Pain VL - 152 IS - 9 N2 - Drug self-administration methods were used to test the hypothesis that rats would self-medicate with a cannabinoid CB(2) agonist to attenuate a neuropathic pain state. Self-medication of the CB(2) agonist (R,S)-AM1241, but not vehicle, attenuated mechanical hypersensitivity produced by spared nerve injury. Switching rats from (R,S)-AM1241 to vehicle self-administration also decreased lever responding in an extinction paradigm. (R,S)-AM1241 self-administration did not alter paw withdrawal thresholds in sham-operated or naive animals. The percentage of active lever responding was similar in naive groups self-administering vehicle or (R,S)-AM1241. The CB(2) antagonist SR144528 blocked both antiallodynic effects of (R,S)-AM1241 self-medication and the percentage of active lever responding in neuropathic (but not naive) rats. Neuropathic and sham groups exhibited similar percentages of active lever responding for (R,S)-AM1241 on a fixed ratio 1 (FR1) schedule. However, neuropathic animals worked harder than shams to obtain (R,S)-AM1241 when the schedule of reinforcement was increased (to FR6). (R,S)-AM1241 self-medication on FR1, FR3, or FR6 schedules attenuated nerve injury-induced mechanical allodynia. (R,S)-AM1241 (900μg intravenously) failed to produce motor ataxia observed after administration of the mixed CB(1)/CB(2) agonist WIN55,212-2 (0.5mg/kg intravenously). Our results suggest that cannabinoid CB(2) agonists may be exploited to treat neuropathic pain with limited drug abuse liability and central nervous system side effects. These studies validate the use of drug self-administration methods for identifying nonpsychotropic analgesics possessing limited abuse potential. These methods offer potential to elucidate novel analgesics that suppress spontaneous neuropathic pain that is not measured by traditional assessments of evoked pain. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/21550725/abstract/Self_medication_of_a_cannabinoid_CB_2__agonist_in_an_animal_model_of_neuropathic_pain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3959(11)00251-X DB - PRIME DP - Unbound Medicine ER -