Garcia-Nicas E, Laird J M A, Cervero F
Department of Physiology, University of Alcalá, Alcalá de Henares, E-28871 Madrid, Spain Research Unit, 'Principe de Asturias' University Hospital, Alcalá de Henares, E-28880 Madrid, Spain.
Pain. 2001 Dec;94(3):283-291. doi: 10.1016/S0304-3959(01)00365-7.
In areas of secondary hyperalgesia, innocuous mechanical stimuli evoke pain (allodynia). We have proposed that this is produced by a central pre-synaptic interaction whereby A beta-fibers evoke spike activity (dorsal root reflexes) in nociceptive afferents (Pain, 68 (1996) 13). This activity should conduct centrally, evoking allodynia, and peripherally, evoking neurogenic vasodilatation. Here we tested this hypothesis by examining the effects of electrical stimulation of A beta-fibers on cutaneous blood flow before and after producing secondary hyperalgesia in anesthetized rats. Cutaneous blood flow was recorded in the hind paw skin innervated by the sural nerve using a laser Doppler flowmeter. The sural nerve was prepared for electrical stimulation, and the evoked activity was recorded from the sciatic nerve in continuity. Electrical stimulation (1 Hz, 4 x 0.2 ms pulses, 20 s) was applied to the sural nerve at 2T (A beta-fibers only) and 4T and 6T (A beta + A delta-fibers). Flux was recorded at baseline and after capsaicin or mustard oil application outside the sural nerve territory. The effects of intravenous administration of the calcitonin gene-related peptide (CGRP) receptor antagonist, alpha-CGRP(8-37), or of section of the sciatic nerve or of the L4-L6 dorsal roots were examined. Selective activation of the sural nerve A beta-fibers reliably evoked increases in cutaneous blood flow close to areas of chemical irritation or skin damage. A beta-fiber-evoked vasodilatation was abolished by sciatic nerve or dorsal root section and had a spatial arrangement and optimal stimulation pattern suggesting a central synaptic interaction similar to that responsible for dorsal root reflexes. The flux increases were dose-dependently and reversibly inhibited by alpha-CGRP(8-37), indicating that the A beta-fiber-evoked vasodilatation resulted from the antidromic activation of nociceptive cutaneous afferent fibers. These results support our hypothesis by showing activation of nociceptive primary afferents by A beta-fibers in areas of allodynia in a manner consistent with a pre-synaptic interaction evoking dorsal root reflexes.
在继发性痛觉过敏区域，无害的机械刺激会引发疼痛（痛觉异常）。我们提出，这是由一种中枢突触前相互作用产生的，即 Aβ 纤维在伤害性传入纤维中诱发动作电位活动（背根反射）（《疼痛》，68 (1996) 13）。这种活动应向中枢传导，引发痛觉异常，向外周传导，引发神经源性血管舒张。在此，我们通过在麻醉大鼠中产生继发性痛觉过敏前后，检测 Aβ 纤维电刺激对皮肤血流的影响，来验证这一假设。使用激光多普勒血流仪记录腓肠神经支配的后爪皮肤的血流情况。准备对腓肠神经进行电刺激，并连续记录坐骨神经诱发的活动。以 2T（仅 Aβ 纤维）、4T 和 6T（Aβ + Aδ 纤维）对腓肠神经施加电刺激（1 Hz，4×0.2 ms 脉冲，20 s）。在基线以及在腓肠神经区域外应用辣椒素或芥子油后记录血流量。检测静脉注射降钙素基因相关肽（CGRP）受体拮抗剂 α-CGRP(8 - 37)、切断坐骨神经或 L4 - L6 背根的影响。选择性激活腓肠神经 Aβ 纤维可靠地诱发化学刺激或皮肤损伤区域附近的皮肤血流增加。坐骨神经或背根切断可消除 Aβ 纤维诱发的血管舒张，且其具有空间分布和最佳刺激模式，提示存在一种类似于引发背根反射的中枢突触相互作用。α-CGRP(8 - 37) 可剂量依赖性且可逆性地抑制血流量增加，表明 Aβ 纤维诱发的血管舒张是由伤害性皮肤传入纤维的逆向激活所致。这些结果通过显示在痛觉异常区域 Aβ 纤维以与引发背根反射的突触前相互作用一致的方式激活伤害性初级传入纤维，支持了我们的假设。
