Zou Xiaoju, Lin Qing, Willis William D
Department of Anatomy and Neuroscience, Marine Biomedical Institute, The University of Texas Medical Branch, Galveston, TX 77555-1069, USA.
Brain Res. 2002 Dec 27;958(2):322-9. doi: 10.1016/s0006-8993(02)03621-1.
Electrophysiological studies have suggested that activity of spinal GABAergic interneurons can be enhanced following intradermal injection of capsaicin (CAP). This activity is proposed to be involved in the generation of dorsal root reflexes (DRRs) that contribute to neurogenic inflammation. We have recently reported that NMDA or non-NMDA antagonists by intrathecal pretreatment attenuate the increased Fos expression in spinal dorsal horn GABAergic neurons after intradermal injection of CAP in rats. Sympathetic efferents have been suggested to modulate inflammatory pain possibly by interactions with primary afferent terminals. In electrophysiological studies by our group, enhancement of the CAP-induced DRRs could be prevented by surgical sympathectomy and blocked by intraarterial pretreatment of the foot with alpha(1)- but not by alpha(2)-adrenoceptor antagonists. In order to determine morphologically if surgical sympathectomy changes the expression of Fos in GABAergic neurons in the lumbosacral spinal cord induced by CAP injection, further experiments were performed using immunofluorescence double-labeling staining at 30 min following CAP or vehicle injection into the glabrous skin of one hind paw of anesthetized rats both in sham-operated and sympathectomized animals. Our results showed that the proportion of Fos-positive GABAergic neuronal profiles was significantly increased following CAP injection (48.8+/-4.76%) compared to vehicle injection (23.8+/-5.1%) in laminae I-V on the ipsilateral side (P<0.05). However, when sympathetic efferents were removed surgically 7-10 days prior to the experiment (n=6), only 32.07+/-9.03% of GABA-immunoreactive neuronal profiles were stained for Fos following CAP injection, a significant reduction in the CAP-evoked Fos-staining of GABAergic neurons after surgical sympathectomy. These findings support our previous electrophysiological studies that GABAergic neurons take part in nociceptive processing within the spinal dorsal horn and suggest that sympathetic efferents may affect nociceptive transduction in the periphery.
电生理研究表明,皮内注射辣椒素(CAP)后,脊髓GABA能中间神经元的活性可增强。这种活性被认为参与了导致神经源性炎症的背根反射(DRR)的产生。我们最近报道,鞘内预处理NMDA或非NMDA拮抗剂可减弱大鼠皮内注射CAP后脊髓背角GABA能神经元中Fos表达的增加。有研究表明,交感传出神经可能通过与初级传入终末的相互作用来调节炎性疼痛。在我们小组的电生理研究中,手术切除交感神经可预防CAP诱导的DRR增强,足部动脉内预处理α1 - 肾上腺素能受体拮抗剂可阻断该增强作用,但α2 - 肾上腺素能受体拮抗剂则无此作用。为了从形态学上确定手术切除交感神经是否会改变CAP注射诱导的腰骶脊髓中GABA能神经元Fos的表达,我们在假手术和交感神经切除的动物中,于麻醉大鼠一侧后爪无毛皮肤注射CAP或赋形剂30分钟后,使用免疫荧光双标记染色进行了进一步实验。我们的结果显示,与同侧I - V层注射赋形剂(23.8±5.1%)相比,注射CAP后Fos阳性GABA能神经元轮廓的比例显著增加(48.8±4.76%)(P<0.05)。然而,在实验前7 - 10天进行手术切除交感神经(n = 6)后,注射CAP后仅32.07±9.03%的GABA免疫反应性神经元轮廓被Fos染色,手术切除交感神经后CAP诱发的GABA能神经元Fos染色显著减少。这些发现支持了我们之前的电生理研究结果,即GABA能神经元参与脊髓背角的伤害性信息处理,并表明交感传出神经可能影响外周的伤害性转导。