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Spinal and peripheral analgesic effects of the CB2 cannabinoid receptor agonist AM1241 in two models of bone cancer-induced pain.
Br J Pharmacol 2010; 160(3):561-73BJ

Abstract

BACKGROUND AND PURPOSE

The activation of CB(2) receptors induces analgesia in experimental models of chronic pain. The present experiments were designed to study whether the activation of peripheral or spinal CB(2) receptors relieves thermal hyperalgesia and mechanical allodynia in two models of bone cancer pain.

EXPERIMENTAL APPROACH

NCTC 2472 osteosarcoma or B16-F10 melanoma cells were intratibially inoculated to C3H/He and C57BL/6 mice. Thermal hyperalgesia was assessed by the unilateral hot plate test and mechanical allodynia by the von Frey test. AM1241 (CB(2) receptor agonist), AM251 (CB(1) receptor antagonist), SR144528 (CB(2) receptor antagonist) and naloxone were used. CB(2) receptor expression was measured by Western blot.

KEY RESULTS

AM1241 (0.3-10 mg.kg(-1)) abolished thermal hyperalgesia and mechanical allodynia in both tumour models. The antihyperalgesic effect was antagonized by subcutaneous, intrathecal or peri-tumour administration of SR144528. In contrast, the antiallodynic effect was inhibited by systemic or intrathecal, but not peri-tumour, injection of SR144528. The effects of AM1241 were unchanged by AM251 but were prevented by naloxone. No change in CB(2) receptor expression was found in spinal cord or dorsal root ganglia.

CONCLUSIONS AND IMPLICATIONS

Spinal CB(2) receptors are involved in the antiallodynic effect induced by AM1241 in two neoplastic models while peripheral and spinal receptors participate in the antihyperalgesic effects. Both effects were mediated by endogenous opiates. The use of drugs that activate CB(2) receptors could be a useful strategy to counteract bone cancer-induced pain symptoms.

Authors+Show Affiliations

Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Asturias, Spain.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20233215

Citation

Curto-Reyes, V, et al. "Spinal and Peripheral Analgesic Effects of the CB2 Cannabinoid Receptor Agonist AM1241 in Two Models of Bone Cancer-induced Pain." British Journal of Pharmacology, vol. 160, no. 3, 2010, pp. 561-73.
Curto-Reyes V, Llames S, Hidalgo A, et al. Spinal and peripheral analgesic effects of the CB2 cannabinoid receptor agonist AM1241 in two models of bone cancer-induced pain. Br J Pharmacol. 2010;160(3):561-73.
Curto-Reyes, V., Llames, S., Hidalgo, A., Menéndez, L., & Baamonde, A. (2010). Spinal and peripheral analgesic effects of the CB2 cannabinoid receptor agonist AM1241 in two models of bone cancer-induced pain. British Journal of Pharmacology, 160(3), pp. 561-73. doi:10.1111/j.1476-5381.2009.00629.x.
Curto-Reyes V, et al. Spinal and Peripheral Analgesic Effects of the CB2 Cannabinoid Receptor Agonist AM1241 in Two Models of Bone Cancer-induced Pain. Br J Pharmacol. 2010;160(3):561-73. PubMed PMID: 20233215.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinal and peripheral analgesic effects of the CB2 cannabinoid receptor agonist AM1241 in two models of bone cancer-induced pain. AU - Curto-Reyes,V, AU - Llames,S, AU - Hidalgo,A, AU - Menéndez,L, AU - Baamonde,A, Y1 - 2010/03/03/ PY - 2010/3/18/entrez PY - 2010/3/18/pubmed PY - 2010/10/15/medline SP - 561 EP - 73 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 160 IS - 3 N2 - BACKGROUND AND PURPOSE: The activation of CB(2) receptors induces analgesia in experimental models of chronic pain. The present experiments were designed to study whether the activation of peripheral or spinal CB(2) receptors relieves thermal hyperalgesia and mechanical allodynia in two models of bone cancer pain. EXPERIMENTAL APPROACH: NCTC 2472 osteosarcoma or B16-F10 melanoma cells were intratibially inoculated to C3H/He and C57BL/6 mice. Thermal hyperalgesia was assessed by the unilateral hot plate test and mechanical allodynia by the von Frey test. AM1241 (CB(2) receptor agonist), AM251 (CB(1) receptor antagonist), SR144528 (CB(2) receptor antagonist) and naloxone were used. CB(2) receptor expression was measured by Western blot. KEY RESULTS: AM1241 (0.3-10 mg.kg(-1)) abolished thermal hyperalgesia and mechanical allodynia in both tumour models. The antihyperalgesic effect was antagonized by subcutaneous, intrathecal or peri-tumour administration of SR144528. In contrast, the antiallodynic effect was inhibited by systemic or intrathecal, but not peri-tumour, injection of SR144528. The effects of AM1241 were unchanged by AM251 but were prevented by naloxone. No change in CB(2) receptor expression was found in spinal cord or dorsal root ganglia. CONCLUSIONS AND IMPLICATIONS: Spinal CB(2) receptors are involved in the antiallodynic effect induced by AM1241 in two neoplastic models while peripheral and spinal receptors participate in the antihyperalgesic effects. Both effects were mediated by endogenous opiates. The use of drugs that activate CB(2) receptors could be a useful strategy to counteract bone cancer-induced pain symptoms. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/20233215/Spinal_and_peripheral_analgesic_effects_of_the_CB2_cannabinoid_receptor_agonist_AM1241_in_two_models_of_bone_cancer_induced_pain_ L2 - https://doi.org/10.1111/j.1476-5381.2009.00629.x DB - PRIME DP - Unbound Medicine ER -