Catheline Gwénaëlle, Le Guen Stéphanie, Besson Jean-Marie
Unité de Recherche de Physiopharmacologie du Système Nerveux, INSERM U 161, and EPHE, 2 rue d'Alésia, 75014 Paris, France.
Pain. 2001 Jun;92(3):389-398. doi: 10.1016/S0304-3959(01)00283-4.
In a model of mononeuropathic pain (chronic constriction injury of the sciatic nerve, CCI), we have demonstrated that light touch stimuli (stroking) to the paw induced Fos-like immunoreactivity (Fos-LI) in the superficial and deep dorsal horn of the rat spinal cord (Catheline et al., Pain 80 (1999a) 347). The efficacy of opioids in neuropathic pain being controversial, we have tested the effects of morphine (0.3, 1 and 3 mg/kg intravenous, i.v.) on this spinal Fos-LI evoked by light tactile stimuli, which could be related to mechanical allodynia. Morphine did not change the level of spinal Fos-LI observed following light touch stimuli in the CCI rats (43 +/- 3, 38 +/- 7, and 37 +/- 4 Fos-LI neurones/40 microm L4-L5 section, respectively, for the three doses versus 32 +/- 4 in the control group). In contrast, the administration of 3 mg/kg of i.v. morphine reduced by 30% the number of Fos-LI neurones induced by heat stimulation (52 degrees C, 15 s duration) in CCI rats (P < 0.05) as in sham-operated rats. These effects were reversed by the systemic administration of naloxone. The lack of effect of morphine on touch-evoked Fos-LI in the superficial dorsal horn reinforces the assertion that dynamic mechanical allodynia is related to information transmitted by A-beta fibres, since opioid receptors are mainly located on thin primary afferent fibres. Our results provide a basis for a certain form of allodynia that is insensitive to morphine.
在单神经病性疼痛模型(坐骨神经慢性缩窄损伤,CCI)中,我们已证明对大鼠爪子进行轻触刺激(抚摸)会在大鼠脊髓的浅背角和深背角诱导出Fos样免疫反应性(Fos-LI)(卡特琳等人,《疼痛》80卷(1999年a期)347页)。由于阿片类药物在神经性疼痛中的疗效存在争议,我们测试了吗啡(0.3、1和3毫克/千克静脉注射,i.v.)对这种由轻触觉刺激诱发的脊髓Fos-LI的影响,这种刺激可能与机械性异常性疼痛有关。吗啡并未改变CCI大鼠在轻触刺激后观察到的脊髓Fos-LI水平(三种剂量下分别为43±3、38±7和37±4个Fos-LI神经元/40微米L4-L5节段,而对照组为32±4)。相比之下,静脉注射3毫克/千克吗啡可使CCI大鼠中由热刺激(52摄氏度,持续15秒)诱导的Fos-LI神经元数量减少30%(P<0.05),假手术大鼠也是如此。这些效应可被全身注射纳洛酮逆转。吗啡对浅背角中触觉诱发的Fos-LI缺乏作用,进一步证明了动态机械性异常性疼痛与A-β纤维传递的信息有关,因为阿片受体主要位于细的初级传入纤维上。我们的结果为某种对吗啡不敏感的异常性疼痛形式提供了依据。