Alvarez Pedro, Hernández Alejandro, Constandil Luis, Infante Claudio, Pelissier Teresa
Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Independencia 1027, PO Box 70000 Santiago 7, Santiago, Chile.
Eur J Neurosci. 2014 Oct;40(8):3264-72. doi: 10.1111/ejn.12685. Epub 2014 Aug 21.
Chronic arthritis (CA) is a common clinical entity associated with persistent pain and limited response to opioid analgesic therapy. However, it is unknown whether these features of CA change depending on its stage of evolution. To address this, in a well-established animal model of CA we studied the time course of electromyographic responses to electrical stimulation of C fibers (C-reflex), pain-like behavior as a response to mechanical nociceptive stimulation, and the inhibition of both responses by a prototypic opioid analgesic, morphine. To induce CA, rats received a single injection of complete Freund's adjuvant into the ankle joint and the C-reflex responses to electrical stimuli or the nociceptive response to paw pressure test were studied 2, 4 or 6 weeks later. The C-reflexes evoked by threshold and supra-threshold electrical stimulation exhibited progressive increases together with enhancement of the nociceptive behavior to mechanical stimulation during induction of monoarthritis. Notably, while systemic morphine produced antinociceptive effects upon both experimental approaches, the effects were markedly reduced during the early stages of CA but enhanced at later stages. These data indicate that C-reflex and pain-like responses evolve in parallel, and are inhibited by morphine in a stage-dependent manner through the induction of CA. The present results may contribute to explain the enhanced pain response and variable analgesic efficacy of opioids that characterize arthritic pain in humans.
慢性关节炎（CA）是一种常见的临床病症，伴有持续性疼痛，对阿片类镇痛治疗反应有限。然而，CA的这些特征是否会因其演变阶段而改变尚不清楚。为了解决这个问题，在一个成熟的CA动物模型中，我们研究了对C纤维电刺激的肌电图反应（C反射）的时间进程、作为对机械性伤害性刺激反应的疼痛样行为，以及一种原型阿片类镇痛药吗啡对这两种反应的抑制作用。为诱导CA，大鼠踝关节单次注射完全弗氏佐剂，并在2、4或6周后研究对电刺激的C反射反应或对 paw压力测试的伤害性反应。在单关节炎诱导期间，由阈值和阈上电刺激诱发的C反射与对机械刺激的伤害性行为增强一起呈现出逐渐增加。值得注意的是，虽然全身应用吗啡在两种实验方法中均产生抗伤害性作用，但在CA早期阶段作用明显减弱，而在后期阶段增强。这些数据表明，C反射和疼痛样反应平行演变，并在CA诱导过程中吗啡以阶段依赖性方式抑制它们。目前的结果可能有助于解释人类关节炎疼痛中阿片类药物增强的疼痛反应和可变的镇痛效果。
