Tags

Type your tag names separated by a space and hit enter

CB1 cannabinoid receptor agonist mouse VD-hemopressin(α) produced supraspinal analgesic activity in the preclinical models of pain.
Brain Res. 2018 02 01; 1680:155-164.BR

Abstract

Mouse VD-hemopressin(α) (VD-Hpα) is an undecapeptide that selectively activates CB1 cannabinoid receptor in in vitro functional tests, and exerts CB1-mediated central antinociception in the mouse tail-flick assay. The aim of the present study was to further investigate the analgesic properties of supraspinal mouse VD-Hpα in a range of preclinical pain models. Our results indicated that the classical cannabinoid agonist WIN 55,212-2 produced supraspinal analgesia in preclinical pain models, which was selectively antagonized by the CB1 antagonist/inverse agonist AM251, but not by the CB2 antagonist AM630. In contrast, in post-operative pain model and phase I of formalin test, intracerebroventricular administration of mouse VD-Hpα induced dose-related analgesia in mice, which were markedly reduced by pretreatment with the CB1 neutral antagonist AM4113, but not AM251, AM630 and the selective antagonists of opioid and Transient Receptor Potential Vanilloid Type 1 (TRPV1) receptors. Furthermore, in the acetic acid-induced visceral pain model, supraspinal administration of mouse VD-Hpα dose-dependently produced analgesic activities and the effects were significantly antagonized by both AM4113 and the TRPV1 receptor antagonist SB366791, but not AM251, AM630 and naloxone. In addition, central injection of mouse VD-Hpα did not have significant effect in phase II of formalin test. Taken together, the present work suggests that the CB1 receptor peptidic agonist mouse VD-Hpα produces supraspinal analgesia in preclinical pain models via a novel CB1 receptor-mediated mechanism, in a manner pharmacologically dissociable from WIN 55,212-2. In addition, TRPV1 receptor might also be involved in mouse VD-Hpα-induced analgesia in a visceral pain model.

Authors+Show Affiliations

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China; Department of Clinical Medicine, Gansu Health Vocational College, 60 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China; Department of Clinical Medicine, Gansu Health Vocational College, 60 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China. Electronic address: wangrui@lzu.edu.cn.Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, China. Electronic address: fangq@lzu.edu.cn.

Pub Type(s)

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

Language

eng

PubMed ID

29274880

Citation

Zheng, Ting, et al. "CB1 Cannabinoid Receptor Agonist Mouse VD-hemopressin(α) Produced Supraspinal Analgesic Activity in the Preclinical Models of Pain." Brain Research, vol. 1680, 2018, pp. 155-164.
Zheng T, Zhang R, Zhang T, et al. CB1 cannabinoid receptor agonist mouse VD-hemopressin(α) produced supraspinal analgesic activity in the preclinical models of pain. Brain Res. 2018;1680:155-164.
Zheng, T., Zhang, R., Zhang, T., Zhang, M. N., Xu, B., Song, J. J., Li, N., Tang, H. H., Wang, P., Wang, R., & Fang, Q. (2018). CB1 cannabinoid receptor agonist mouse VD-hemopressin(α) produced supraspinal analgesic activity in the preclinical models of pain. Brain Research, 1680, 155-164. https://doi.org/10.1016/j.brainres.2017.12.013
Zheng T, et al. CB1 Cannabinoid Receptor Agonist Mouse VD-hemopressin(α) Produced Supraspinal Analgesic Activity in the Preclinical Models of Pain. Brain Res. 2018 02 1;1680:155-164. PubMed PMID: 29274880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CB1 cannabinoid receptor agonist mouse VD-hemopressin(α) produced supraspinal analgesic activity in the preclinical models of pain. AU - Zheng,Ting, AU - Zhang,Run, AU - Zhang,Ting, AU - Zhang,Meng-Na, AU - Xu,Biao, AU - Song,Jing-Jing, AU - Li,Ning, AU - Tang,Hong-Hai, AU - Wang,Pei, AU - Wang,Rui, AU - Fang,Quan, Y1 - 2017/12/21/ PY - 2017/01/04/received PY - 2017/10/15/revised PY - 2017/12/12/accepted PY - 2017/12/25/pubmed PY - 2018/8/15/medline PY - 2017/12/25/entrez KW - Antinociception KW - Cannabinoids KW - Formalin pain KW - Post-operative pain KW - VD-hemopressin(α) KW - Visceral pain SP - 155 EP - 164 JF - Brain research JO - Brain Res VL - 1680 N2 - Mouse VD-hemopressin(α) (VD-Hpα) is an undecapeptide that selectively activates CB1 cannabinoid receptor in in vitro functional tests, and exerts CB1-mediated central antinociception in the mouse tail-flick assay. The aim of the present study was to further investigate the analgesic properties of supraspinal mouse VD-Hpα in a range of preclinical pain models. Our results indicated that the classical cannabinoid agonist WIN 55,212-2 produced supraspinal analgesia in preclinical pain models, which was selectively antagonized by the CB1 antagonist/inverse agonist AM251, but not by the CB2 antagonist AM630. In contrast, in post-operative pain model and phase I of formalin test, intracerebroventricular administration of mouse VD-Hpα induced dose-related analgesia in mice, which were markedly reduced by pretreatment with the CB1 neutral antagonist AM4113, but not AM251, AM630 and the selective antagonists of opioid and Transient Receptor Potential Vanilloid Type 1 (TRPV1) receptors. Furthermore, in the acetic acid-induced visceral pain model, supraspinal administration of mouse VD-Hpα dose-dependently produced analgesic activities and the effects were significantly antagonized by both AM4113 and the TRPV1 receptor antagonist SB366791, but not AM251, AM630 and naloxone. In addition, central injection of mouse VD-Hpα did not have significant effect in phase II of formalin test. Taken together, the present work suggests that the CB1 receptor peptidic agonist mouse VD-Hpα produces supraspinal analgesia in preclinical pain models via a novel CB1 receptor-mediated mechanism, in a manner pharmacologically dissociable from WIN 55,212-2. In addition, TRPV1 receptor might also be involved in mouse VD-Hpα-induced analgesia in a visceral pain model. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/29274880/CB1_cannabinoid_receptor_agonist_mouse_VD_hemopressin_α__produced_supraspinal_analgesic_activity_in_the_preclinical_models_of_pain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(17)30547-4 DB - PRIME DP - Unbound Medicine ER -