Development and expression of neuropathic pain in CB1 knockout mice

被引:33
作者
Castañé, A
Célérier, E
Martín, M
Ledent, C
Parmentier, M
Maldonado, R
Valverde, O
机构
[1] Univ Pompeu Fabra, Lab Neurofarmacol, Fac Ciencias Salut & Vida Ciencies Expt & Salut, Barcelona 08003, Spain
[2] Free Univ Brussels, IRIBHM, B-1070 Brussels, Belgium
关键词
allodynia; CB1 cannabinoid receptors; gabapentin; hyperalgesia; neuropathic pain;
D O I
10.1016/j.neuropharm.2005.07.022
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Neuropathic pain is a clinical manifestation characterized by the presence of spontaneous pain, allodynia and hyperalgesia. Here, we have evaluated the involvement of CB1 cannabinoid receptors in the development and expression of neuropathic pain. For this purpose, partial ligation of the sciatic nerve was performed in CB1 cannabinoid receptor knockout mice and their wild-type litter-mates. The development of mechanical and thermal allodynia, and thermal hyperalgesia was evaluated by using the von Frey filaments, cold-plate and plantar tests, respectively. Pre-surgical tactile and thermal withdrawal thresholds were similar in both genotypes. In wild-type mice, sciatic nerve injury led to a neuropathic pain syndrome characterized by a marked and long-lasting reduction of the paw withdrawal thresholds to mechanical and thermal stimuli. These manifestations developed similarly in mice lacking CB1 cannabinoid receptors. We have also investigated the consequences of gabapentin administration in these animals. Gabapentin (50 mg/kg/day, i.p.) induced a similar suppression of mechanical and thermal allodynia in both wild-type and CB1 knockout mice. Mild differences between genotypes were observed concerning the effect of gabapentin in the expression of thermal hyperalgesia. Taken together, our results indicate that CB1 cannabinoid receptors are not critically implicated in the development of neuropathic pain nor in the anti-allodynic and anti-hyperalgesic effects of gabapentin in this model. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:111 / 122
页数:12
相关论文
共 47 条
[41]   Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action [J].
Sindrup, SH ;
Jensen, TS .
PAIN, 1999, 83 (03) :389-400
[42]  
Spina E, 2004, EPILEPTIC DISORD, V6, P57
[43]   Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin [J].
Ständer, S ;
Schmelz, M ;
Metze, D ;
Luger, T ;
Rukwied, R .
JOURNAL OF DERMATOLOGICAL SCIENCE, 2005, 38 (03) :177-188
[44]   Reduction of stress-induced analgesia but not of exogenous opioid effects in mice lacking CB1 receptors [J].
Valverde, O ;
Ledent, C ;
Beslot, F ;
Parmentier, M ;
Roques, BP .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2000, 12 (02) :533-539
[45]  
Wood John N, 2004, Novartis Found Symp, V261, P32
[46]   Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models [J].
Zhang, J ;
Hoffert, C ;
Vu, HK ;
Groblewski, T ;
Ahmad, S ;
O'Donnell, D .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2003, 17 (12) :2750-2754
[47]   Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice [J].
Zimmer, A ;
Zimmer, AM ;
Hohmann, AG ;
Herkenham, M ;
Bonner, TI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (10) :5780-5785