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Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain.
Pharmacol Biochem Behav 2008; 91(1):38-46PB

Abstract

Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model. Furthermore, this treatment strategy was not found to induce measurable CNS related side effects or tolerance. Cancer cell viability assays and bone volume fraction assessed by micro computed tomography (microCT) demonstrated that these effects were not due to changes in cancer progression. The difference in WIN 55,212-2 efficacy between the bone cancer and neuropathic pain models may reflect the different pain generating mechanisms, which may be utilized in designing new therapeutic drugs.

Authors+Show Affiliations

Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, Copenhagen University, Denmark.No 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)

Journal Article

Language

eng

PubMed ID

18611408

Citation

Hald, Andreas, et al. "Differential Effects of Repeated Low Dose Treatment With the Cannabinoid Agonist WIN 55,212-2 in Experimental Models of Bone Cancer Pain and Neuropathic Pain." Pharmacology, Biochemistry, and Behavior, vol. 91, no. 1, 2008, pp. 38-46.
Hald A, Ding M, Egerod K, et al. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain. Pharmacol Biochem Behav. 2008;91(1):38-46.
Hald, A., Ding, M., Egerod, K., Hansen, R. R., Konradsen, D., Jørgensen, S. G., ... Heegaard, A. M. (2008). Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain. Pharmacology, Biochemistry, and Behavior, 91(1), pp. 38-46. doi:10.1016/j.pbb.2008.04.021.
Hald A, et al. Differential Effects of Repeated Low Dose Treatment With the Cannabinoid Agonist WIN 55,212-2 in Experimental Models of Bone Cancer Pain and Neuropathic Pain. Pharmacol Biochem Behav. 2008;91(1):38-46. PubMed PMID: 18611408.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain. AU - Hald,Andreas, AU - Ding,Ming, AU - Egerod,Kristoffer, AU - Hansen,Rikke R, AU - Konradsen,Dorthe, AU - Jørgensen,Stine G, AU - Atalay,Baris, AU - Nasser,Arafat, AU - Bjerrum,Ole J, AU - Heegaard,Anne-Marie, Y1 - 2008/06/20/ PY - 2007/09/06/received PY - 2008/03/30/revised PY - 2008/04/29/accepted PY - 2008/7/10/pubmed PY - 2008/11/7/medline PY - 2008/7/10/entrez SP - 38 EP - 46 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 91 IS - 1 N2 - Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model. Furthermore, this treatment strategy was not found to induce measurable CNS related side effects or tolerance. Cancer cell viability assays and bone volume fraction assessed by micro computed tomography (microCT) demonstrated that these effects were not due to changes in cancer progression. The difference in WIN 55,212-2 efficacy between the bone cancer and neuropathic pain models may reflect the different pain generating mechanisms, which may be utilized in designing new therapeutic drugs. SN - 0091-3057 UR - https://www.unboundmedicine.com/medline/citation/18611408/Differential_effects_of_repeated_low_dose_treatment_with_the_cannabinoid_agonist_WIN_55212_2_in_experimental_models_of_bone_cancer_pain_and_neuropathic_pain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(08)00225-6 DB - PRIME DP - Unbound Medicine ER -