Potrebic S B, Fields H L, Mason P
Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02143.
J Neurosci. 1994 Mar;14(3 Pt 2):1655-65. doi: 10.1523/JNEUROSCI.14-03-01655.1994.
Neurons in the rostral ventromedial medulla (RVM) are the major source of serotonergic projections to the dorsal horn. A large body of evidence implicates RVM serotonergic neurons in the modulation of spinal nociceptive transmission. Three physiological classes of RVM neurons, on, off, and neutral cells, are postulated to have different nociceptive modulatory effects on spinal nocifensor reflexes. This study was undertaken to determine which RVM cell class(es) contains 5-HT. In anesthetized rats, RVM neurons were identified by their responses to noxious cutaneous stimuli, intracellularly labeled, and processed for 5-HT immunocytochemistry. Labeled neurons were examined with epifluorescence and imaged using a confocal laser microscope. A total of 25 RVM neurons were intracellularly labeled. No off (n = 9) or on (n = 8) cells were serotonergic. Half of the neutral cells (4 of 8) demonstrated 5-HT immunoreactivity. These results call for a reevaluation of the mechanisms of RVM modulatory influence on spinal cord nociceptive transmission. The finding that some neutral cells are serotonergic strongly suggests that serotonergic neutral cells are involved in the modulation of spinal nociceptive transmission. Additionally, inhibition of spinal nociceptive transmission by off cells is unlikely to involve 5-HT release. Finally, since opioid administration does not alter the firing of RVM neutral cells, the results of the present study indicate that serotonergic RVM neurons do not directly mediate the effects of supraspinal opioids in the rat.
延髓头端腹内侧区(RVM)的神经元是向背角投射5-羟色胺能纤维的主要来源。大量证据表明,RVM的5-羟色胺能神经元参与脊髓伤害性感受传递的调节。RVM神经元分为三种生理类型:开细胞、关细胞和中性细胞,推测它们对脊髓伤害性反射具有不同的伤害性调制作用。本研究旨在确定哪类RVM细胞含有5-羟色胺(5-HT)。在麻醉大鼠中,通过对有害皮肤刺激的反应来识别RVM神经元,进行细胞内标记,并进行5-HT免疫细胞化学处理。用落射荧光检查标记的神经元,并用共聚焦激光显微镜成像。总共25个RVM神经元被细胞内标记。没有一个关细胞(n = 9)或开细胞(n = 8)是5-羟色胺能的。一半的中性细胞(8个中的4个)显示出5-HT免疫反应性。这些结果要求重新评估RVM对脊髓伤害性感受传递的调制影响机制。一些中性细胞是5-羟色胺能的这一发现强烈表明,5-羟色胺能中性细胞参与脊髓伤害性感受传递的调制。此外,关细胞对脊髓伤害性感受传递的抑制不太可能涉及5-HT释放。最后,由于给予阿片类药物不会改变RVM中性细胞的放电,本研究结果表明,RVM的5-羟色胺能神经元不直接介导大鼠脊髓上阿片类药物的作用。