Department of Human Morphology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon Department of Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon Department of Psychiatry, Faculty of Medicine, American University of Beirut, Beirut, Lebanon Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Pain. 2010 Apr;149(1):89-99. doi: 10.1016/j.pain.2010.01.014. Epub 2010 Feb 13.
Attenuation of neuropathic manifestations in experimental animals, by lidocaine injection in the rostral ventro-medial medulla (RVM), has been traditionally attributed to selective block of a descending pain facilitatory system. However, the presence of descending fibers carrying this effect and the selective action of lidocaine on the facilitatory neurons, have not been supported by convincing experimental evidence. The present study aimed to investigate the mechanisms underlying the hypoalgesic action of lidocaine injection in the brainstem. Several groups of rats were subjected to mononeuropathy on their left hind paws, according to the model of spared nerve injury, and were subsequently implanted with guide cannulae in the RVM. After recovery, rats received injections of lidocaine, GABA and glycine agonists or antagonists and their effects were assessed on behavioral tests of allodynia and hyperalgesia. Injections of lidocaine at doses ranging between 0.05% and 2% produced attenuation at high doses and no effects or increasing hyperalgesia at low doses. GABA and glycine agonists increased neuropathic manifestations while their antagonists elicited the opposite effects. A combined injection of GABA agonist or glycine with lidocaine (0.5%) prevented the inhibitory effects of lidocaine injection alone. Our results are in line with the abundant documentation on the alteration of the function of inhibitory neurons by lidocaine and reveal a possible action of the injected high doses on the GABAergic and glycinergic neurons in the RVM. The resulting block of the inhibitory tone exerted by these neurons can lead to a release of the descending pain inhibitory systems.
在实验动物中，通过向延髓头端腹内侧（RVM）注射利多卡因来减轻神经病理性表现，传统上归因于对下行疼痛易化系统的选择性阻断。然而，携带这种效应的下行纤维的存在以及利多卡因对易化神经元的选择性作用，并没有得到令人信服的实验证据的支持。本研究旨在探讨 RVM 内注射利多卡因产生镇痛作用的机制。几组大鼠的左后爪接受单神经损伤模型的神经病变，随后在 RVM 中植入引导套管。恢复后，大鼠接受利多卡因、GABA 和甘氨酸激动剂或拮抗剂的注射，并在所有痛觉过敏和痛觉过敏的行为测试中评估其效果。在 0.05%至 2%的剂量范围内注射利多卡因，高剂量时产生抑制作用，低剂量时无作用或增加痛觉过敏。GABA 和甘氨酸激动剂增加神经病理性表现，而其拮抗剂则产生相反的效果。GABA 激动剂或甘氨酸与利多卡因（0.5%）的联合注射可防止单独注射利多卡因的抑制作用。我们的结果与关于利多卡因改变抑制性神经元功能的大量文献一致，并揭示了注射高剂量药物可能对 RVM 中的 GABA 能和甘氨酸能神经元产生作用。由此产生的对这些神经元施加的抑制性张力的阻断可导致下行疼痛抑制系统的释放。
