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Self-medication of a cannabinoid CB2 agonist in an animal model of neuropathic pain.

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.

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  • Authors+Show Affiliations

    ,

    Neuroscience and Behavior Program, Department of Psychology, University of Georgia, Athens, GA, USA.

    , , ,

    Source

    Pain 152:9 2011 Sep pg 1976-87

    MeSH

    Animals
    Cannabinoids
    Conditioning, Operant
    Disease Models, Animal
    Male
    Neuralgia
    Rats
    Rats, Sprague-Dawley
    Receptor, Cannabinoid, CB2
    Self Medication

    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 -