Andreev N, Urban L, Dray A
Sandoz Institute for Medical Research, London, U.K.
Neuroscience. 1994 Feb;58(4):793-8. doi: 10.1016/0306-4522(94)90456-1.
Changes in chemical sensitivity of peripheral nociceptors following injury or inflammation have been studied in in vitro preparation of the saphenous nerve-hind paw skin from adult rats. Heat hyperalgesia in the hind paw was induced by a prior ultraviolet irradiation and the skin from these animals was investigated five days later. Polymodal nociceptors were quiescent in normal skin but were spontaneously active in the majority of fibres after ultraviolet exposure. Capsaicin-induced activation of fine fibres was enhanced after ultraviolet pretreatment. Direct administration of morphine, DAGOL (mu-receptor agonist) and U-69593 (kappa-receptor agonist), but not DPDPE (delta-receptor agonist) to the receptive field produced a concentration-related and naloxone-reversible suppression of spontaneous firing in polymodal nociceptors of ultraviolet-treated skin. Morphine did not reduce the activity of fibres in normal skin when these were driven by KCl depolarization. These data show that polymodal nociceptors change their activity and sensitivity to exogenous chemicals following the induction of peripheral hyperalgesia by ultraviolet irradiation. Specifically, evidence is provided for the expression of opioid sensitivity and inhibition of polymodal nociceptor activity through mu- and kappa-opioid receptors. These observations may account for peripheral antinociceptive actions of opioids during specific states of peripheral hyperalgesia.
利用成年大鼠隐神经 - 后爪皮肤的体外制备模型，研究了损伤或炎症后外周伤害性感受器化学敏感性的变化。后爪热痛觉过敏通过预先的紫外线照射诱导产生，在五天后对这些动物的皮肤进行研究。多模式伤害性感受器在正常皮肤中处于静息状态，但在紫外线照射后，大多数纤维会自发活动。紫外线预处理后，辣椒素诱导的细纤维激活增强。向感受野直接给予吗啡、DAGOL（μ受体激动剂）和U - 69593（κ受体激动剂），而非DPDPE（δ受体激动剂），可产生与浓度相关且可被纳洛酮逆转的对紫外线处理皮肤中多模式伤害性感受器自发放电的抑制作用。当正常皮肤中的纤维由氯化钾去极化驱动时，吗啡不会降低其活性。这些数据表明，在紫外线照射诱导外周痛觉过敏后，多模式伤害性感受器会改变其活性以及对外源化学物质的敏感性。具体而言，有证据表明多模式伤害性感受器通过μ和κ阿片受体表达阿片敏感性并抑制其活性。这些观察结果可能解释了在特定外周痛觉过敏状态下阿片类药物的外周抗伤害感受作用。
