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The non-selective cannabinoid receptor agonist WIN 55,212-2 attenuates responses of C-fiber nociceptors in a murine model of cancer pain.
Neuroscience. 2013 Sep 05; 247:84-94.N

Abstract

Pain from cancer can be severe, difficult to treat, and greatly diminishes patients' quality of life. It is therefore important to gain new information on the mechanisms of cancer pain and develop new treatment strategies. We have used a murine model of bone cancer pain to investigate underlying peripheral neural mechanisms and novel treatment approaches. In this model, implantation of fibrosarcoma cells into and around the calcaneous bone produces mechanical and thermal hyperalgesia in mice. C-fiber nociceptors in tumor-bearing mice develop spontaneous ongoing activity and sensitization to thermal stimuli. However, it is unclear whether sensitization of nociceptors to mechanical stimuli underlies the mechanical hyperalgesia seen in tumor-bearing mice. We therefore examined responses of C-fiber nociceptors to suprathreshold mechanical stimuli in tumor-bearing mice and found they did not differ from those of C-nociceptors in control mice. Thus, sensitization of C-fiber nociceptors to mechanical stimulation does not appear to underlie tumor-evoked mechanical hyperalgesia in this murine model of bone cancer pain. We also examined the effect of the non-selective cannabinoid receptor agonist, WIN 55,212-2, on spontaneous activity and responses evoked by mechanical stimuli of C-fiber nociceptors innervating the tumor-bearing paw. Selective CB1 and CB2 antagonists were administered to determine the contribution of each receptor subtype to the effects of WIN 55,212-2. Intraplantar administration of WIN 55,212-2 attenuated spontaneous discharge and responses evoked by mechanical stimulation of C-fiber nociceptors. These effects were inhibited by prior intraplantar administration of selective CB1 (AM281) or CB2 (AM630) receptor antagonists but not by vehicle. These results indicate that activation of either CB1 or CB2 receptors reduced the spontaneous activity of C-fiber nociceptors associated with tumor growth as well as their evoked responses. Our results provide further evidence that activation of peripheral cannabinoid receptors may be a useful target for the treatment of cancer pain.

Authors+Show Affiliations

Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, MN 55447, United States.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23673278

Citation

Uhelski, M L., et al. "The Non-selective Cannabinoid Receptor Agonist WIN 55,212-2 Attenuates Responses of C-fiber Nociceptors in a Murine Model of Cancer Pain." Neuroscience, vol. 247, 2013, pp. 84-94.
Uhelski ML, Cain DM, Harding-Rose C, et al. The non-selective cannabinoid receptor agonist WIN 55,212-2 attenuates responses of C-fiber nociceptors in a murine model of cancer pain. Neuroscience. 2013;247:84-94.
Uhelski, M. L., Cain, D. M., Harding-Rose, C., & Simone, D. A. (2013). The non-selective cannabinoid receptor agonist WIN 55,212-2 attenuates responses of C-fiber nociceptors in a murine model of cancer pain. Neuroscience, 247, 84-94. https://doi.org/10.1016/j.neuroscience.2013.05.003
Uhelski ML, et al. The Non-selective Cannabinoid Receptor Agonist WIN 55,212-2 Attenuates Responses of C-fiber Nociceptors in a Murine Model of Cancer Pain. Neuroscience. 2013 Sep 5;247:84-94. PubMed PMID: 23673278.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The non-selective cannabinoid receptor agonist WIN 55,212-2 attenuates responses of C-fiber nociceptors in a murine model of cancer pain. AU - Uhelski,M L, AU - Cain,D M, AU - Harding-Rose,C, AU - Simone,D A, Y1 - 2013/05/11/ PY - 2013/02/23/received PY - 2013/04/24/revised PY - 2013/05/03/accepted PY - 2013/5/16/entrez PY - 2013/5/16/pubmed PY - 2014/3/19/medline KW - AM281 KW - AM630 KW - ANOVA KW - C-mechanoheat nociceptors KW - C-mechanonociceptors KW - CM KW - CMH KW - CV KW - DRG KW - IQR KW - PBS KW - PID KW - TRP KW - TRP ankyrin 1 KW - TRP vanilloid 1 KW - TRPA1 KW - TRPV1 KW - analysis of variance KW - conduction velocity KW - dorsal root ganglion KW - electrophysiology KW - interquartile range KW - mouse KW - peripheral nerve KW - phosphate-buffered saline KW - post-implantation day KW - tibial nerve KW - transient receptor potential SP - 84 EP - 94 JF - Neuroscience JO - Neuroscience VL - 247 N2 - Pain from cancer can be severe, difficult to treat, and greatly diminishes patients' quality of life. It is therefore important to gain new information on the mechanisms of cancer pain and develop new treatment strategies. We have used a murine model of bone cancer pain to investigate underlying peripheral neural mechanisms and novel treatment approaches. In this model, implantation of fibrosarcoma cells into and around the calcaneous bone produces mechanical and thermal hyperalgesia in mice. C-fiber nociceptors in tumor-bearing mice develop spontaneous ongoing activity and sensitization to thermal stimuli. However, it is unclear whether sensitization of nociceptors to mechanical stimuli underlies the mechanical hyperalgesia seen in tumor-bearing mice. We therefore examined responses of C-fiber nociceptors to suprathreshold mechanical stimuli in tumor-bearing mice and found they did not differ from those of C-nociceptors in control mice. Thus, sensitization of C-fiber nociceptors to mechanical stimulation does not appear to underlie tumor-evoked mechanical hyperalgesia in this murine model of bone cancer pain. We also examined the effect of the non-selective cannabinoid receptor agonist, WIN 55,212-2, on spontaneous activity and responses evoked by mechanical stimuli of C-fiber nociceptors innervating the tumor-bearing paw. Selective CB1 and CB2 antagonists were administered to determine the contribution of each receptor subtype to the effects of WIN 55,212-2. Intraplantar administration of WIN 55,212-2 attenuated spontaneous discharge and responses evoked by mechanical stimulation of C-fiber nociceptors. These effects were inhibited by prior intraplantar administration of selective CB1 (AM281) or CB2 (AM630) receptor antagonists but not by vehicle. These results indicate that activation of either CB1 or CB2 receptors reduced the spontaneous activity of C-fiber nociceptors associated with tumor growth as well as their evoked responses. Our results provide further evidence that activation of peripheral cannabinoid receptors may be a useful target for the treatment of cancer pain. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/23673278/The_non_selective_cannabinoid_receptor_agonist_WIN_55212_2_attenuates_responses_of_C_fiber_nociceptors_in_a_murine_model_of_cancer_pain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(13)00414-4 DB - PRIME DP - Unbound Medicine ER -