Center for Biomedical Research on Pain, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
J Physiol. 2010 Nov 1;588(Pt 21):4177-88. doi: 10.1113/jphysiol.2010.196923.
In conscious rats, we investigated the change of nociceptive paw withdrawal reflexes elicited by mechanical and heat stimuli during intramuscular (i.m.) 5.8% hypertonic (HT) saline elicited muscle nociception. i.m. injection of HT saline caused rapid onset, long lasting (around 7 days), bilateral mechanical hyperalgesia, while it induced bilateral, slower onset (1 day after the HT saline injection), long-term (about 1-2 weeks) heat hypoalgesia. Ipsilateral topical pre-treatment of the sciatic nerve with 1% capsaicin significantly prevented the occurrence of both the bilateral mechanical hyperalgesia and the contralateral heat hypoalgesia. Intrathecal administration of either 6-hydroxydopamine hydrobromide (6-OHDA) or 5,7-dihydroxytryptamine (5,7-DHT), and intraperitoneal injection of naloxone all markedly attenuated the HT saline induced bilateral heat hypoalgesia, but not the mechanical hyperalgesia. Combined with experiments with lesioning of the rostroventral medulla with kainic acid, the present data indicate that unilateral i.m. injection of HT saline elicits time-dependent bilateral long-term mechanical hyperalgesia and heat hypoalgesia, which were modulated by descending facilitatory and inhibitory controls, respectively. We hypothesize that supraspinal structures may function to discriminate between afferent noxious inputs mediated by Aδ- and C-fibres, either facilitating Aδ-fibre mediated responses or inhibiting C-fibre mediated activities. However, this discriminative function is physiologically silent or inactive, and can be triggered by stimulation of peripheral C-fibre afferents. Importantly, in contrast to the rapid onset of descending facilitation, the late occurrence of descending inhibition suggests a requirement of continuous C-fibre input and temporal summation. Thus, a reduction of C-fibre input using exogenous analgesic agents, i.e. opioids, may counteract the endogenous descending inhibition.
在有意识的大鼠中，我们研究了肌肉内（i.m.）5.8%高渗（HT）盐水引起肌肉疼痛时，机械和热刺激引起的伤害性爪回缩反射的变化。i.m.注射 HT 盐水会导致快速发作、持续时间长（约 7 天）、双侧机械性痛觉过敏，而它会引起双侧、较慢发作（HT 盐水注射后 1 天）、长期（约 1-2 周）热痛觉减退。同侧坐骨神经 1%辣椒素的局部预处理显著预防了双侧机械性痛觉过敏和对侧热痛觉减退的发生。鞘内给予 6-羟多巴胺氢溴酸盐（6-OHDA）或 5,7-二羟基色胺（5,7-DHT），以及腹腔内注射纳洛酮，均可显著减弱 HT 盐水引起的双侧热痛觉减退，但不能减弱机械性痛觉过敏。结合用海人酸损毁延髓腹侧前部的实验，本研究数据表明，单侧 i.m.注射 HT 盐水会引起时间依赖性双侧长期机械性痛觉过敏和热痛觉减退，分别由下行促进和抑制控制调节。我们假设，中枢神经系统结构可能有助于区分由 Aδ和 C 纤维介导的传入伤害性输入，促进 Aδ纤维介导的反应或抑制 C 纤维介导的活动。然而，这种辨别功能在生理上是沉默或不活跃的，可以通过刺激外周 C 纤维传入纤维来触发。重要的是，与下行促进的快速发作相比，下行抑制的迟发表明需要持续的 C 纤维输入和时间总和。因此，使用外源性镇痛剂（即阿片类药物）减少 C 纤维输入可能会对抗内源性下行抑制。
