Sagar Devi Rani, Kelly Sara, Millns Paul J, O'Shaughnessey Celestine T, Kendall David A, Chapman Victoria
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG9 2UH, UK.
Eur J Neurosci. 2005 Jul;22(2):371-9. doi: 10.1111/j.1460-9568.2005.04206.x.
Cannabinoid 2 (CB2) receptor mediated antinociception and increased levels of spinal CB2 receptor mRNA are reported in neuropathic Sprague-Dawley rats. The aim of this study was to provide functional evidence for a role of peripheral, vs. spinal, CB2 and cannabinoid 1 (CB1) receptors in neuropathic rats. Effects of the CB2 receptor agonist, JWH-133, and the CB1 receptor agonist, arachidonyl-2-chloroethylamide (ACEA), on primary afferent fibres were determined by calcium imaging studies of adult dorsal root ganglion (DRG) neurons taken from neuropathic and sham-operated rats. Capsaicin (100 nm) increased [Ca2+]i in DRG neurons from sham and neuropathic rats. JWH-133 (3 microm) or ACEA (1 microm) significantly (P<0.001) attenuated capsaicin-evoked calcium responses in DRG neurons in neuropathic and sham-operated rats. The CB2 receptor antagonist, SR144528, (1 microm) significantly inhibited the effects of JWH-133. Effects of ACEA were significantly inhibited by the CB1 receptor antagonist SR141716A (1 microm). In vivo experiments evaluated the effects of spinal administration of JWH-133 (8-486 ng/50 microL) and ACEA (0.005-500 ng/50 microL) on mechanically evoked responses of neuropathic and sham-operated rats. Spinal JWH-133 attenuated mechanically evoked responses of spinal neurons in neuropathic, but not sham-operated rats. These inhibitory effects were blocked by SR144528 (0.001 microg/50 microL). Spinal ACEA inhibited mechanically evoked responses of neuropathic and sham-operated rats, these effects were blocked by SR141716A (0.01 microg/50 microL). Our data provide evidence for a functional role of CB2, as well as CB1 receptors on DRG neurons in sham and neuropathic rats. At the level of the spinal cord, CB2 receptors have inhibitory effects in neuropathic, but not sham-operated rats suggesting that spinal CB2 may be an important analgesic target.
据报道，在神经性疼痛的斯普拉格-道利大鼠中，大麻素2（CB2）受体介导了抗伤害感受作用，且脊髓CB2受体mRNA水平升高。本研究的目的是为外周与脊髓的CB2和大麻素1（CB1）受体在神经性大鼠中的作用提供功能证据。通过对取自神经性和假手术大鼠的成年背根神经节（DRG）神经元进行钙成像研究，确定了CB2受体激动剂JWH-133和CB1受体激动剂花生四烯酸-2-氯乙酯（ACEA）对初级传入纤维的影响。辣椒素（100 nM）可增加假手术和神经性大鼠DRG神经元中的[Ca2+]i。JWH-133（3 μM）或ACEA（1 μM）可显著（P<0.001）减弱辣椒素诱发的神经性和假手术大鼠DRG神经元中的钙反应。CB2受体拮抗剂SR144528（1 μM）可显著抑制JWH-133的作用。CB1受体拮抗剂SR141716A（1 μM）可显著抑制ACEA的作用。体内实验评估了脊髓注射JWH-1（8-486 ng/50 μL）和ACEA（0.005-500 ng/50 μL）对神经性和假手术大鼠机械诱发反应（MER）的影响。脊髓注射JWH-133可减弱神经性大鼠而非假手术大鼠脊髓神经元的机械诱发反应。这些抑制作用可被SR144528（0.001 μg/50 μL）阻断。脊髓注射ACEA可抑制神经性和假手术大鼠的机械诱发反应，这些作用可被SR141716A（0.01 μg/50 μL）阻断。我们的数据为CB2以及CB1受体在假手术和神经性大鼠DRG神经元中的功能作用提供了证据。在脊髓水平，CB2受体在神经性大鼠而非假手术大鼠中具有抑制作用，这表明脊髓CB2可能是一个重要的镇痛靶点。
