Leng Changlong, Chen Lin, Gong Xiaokang, Ma Baomiao, Gan Weimin, Si Yuanren, Xiao Huaqiao, Li Chaoying
Department of Neuropharmacology, Wuhan Institute of Biomedical Sciences, Jianghan University.
Department of Psychiatry, Wanji Psychiatric Hospital, Wuhan, China.
Neuroreport. 2018 May 23;29(8):678-684. doi: 10.1097/WNR.0000000000001018.
Drug dependence and withdrawal syndrome induced by abrupt cessation of opioid administration remain a severe obstacle in the clinical treatment of chronic pain and opioid drug addiction. One of the key symptoms during opioid withdrawal is hyperalgesia. The mechanism of opioid withdrawal-induced hyperalgesia remains unclear. P2X2 and P2X3 receptors, members of P2X receptor subunits, act as the integrator of multiple forms of noxious stimuli and play an important role in nociception transduction of chronic neuropathic and inflammatory pain. The process of P2X2 and P2X3 receptor antagonism inhibits inflammatory hyperalgesia, involving the spinal opioid system. However, the role of P2X receptors involved in opioid withdrawal-induced hyperalgesia has seldom been discussed. To explore the role of P2X2 and P2X3 receptors in the opioid-induced hyperalgesia, heroin self-administration rats were adopted, and the thermal and mechanical nociceptive thresholds were evaluated using the paw withdrawal test after abstinence from heroin for 8 days. In addition, the expressions of P2X2 and P2X3 receptors in dorsal root ganglia were analyzed by immunofluorescence. The results showed that after 8 days of abstinence, heroin self-administration rats showed thermal hyperalgesia and mechanical allodynia. Meanwhile, the expressions of the P2X2 and P2X3 receptors in dorsal root ganglia were increased. These results suggest that upregulation of P2X2 and P2X3 receptors might partially play a role in heroin withdrawal-induced hyperalgesia.
阿片类药物给药突然中断所导致的药物依赖和戒断综合征，仍然是慢性疼痛临床治疗及阿片类药物成瘾治疗中的严重障碍。阿片类药物戒断期间的关键症状之一是痛觉过敏。阿片类药物戒断所致痛觉过敏的机制尚不清楚。P2X2和P2X3受体作为P2X受体亚基成员，充当多种形式伤害性刺激的整合器，并在慢性神经性疼痛和炎性疼痛的伤害性感受转导中发挥重要作用。P2X2和P2X3受体拮抗过程可抑制炎性痛觉过敏，这一过程涉及脊髓阿片系统。然而，P2X受体在阿片类药物戒断所致痛觉过敏中的作用很少被探讨。为探究P2X2和P2X3受体在阿片类药物所致痛觉过敏中的作用，采用海洛因自身给药大鼠，在戒断海洛因8天后，通过足趾撤离试验评估热痛觉和机械痛觉阈值。此外，通过免疫荧光分析背根神经节中P2X2和P2X3受体的表达。结果显示，戒断8天后，海洛因自身给药大鼠出现热痛觉过敏和机械性异常性疼痛。同时，背根神经节中P2X2和P2X3受体的表达增加。这些结果表明，P2X2和P2X3受体的上调可能在海洛因戒断所致痛觉过敏中部分发挥作用。
