Kiefel J M, Cooper M L, Bodnar R J
Department of Psychology, Queens College, City University of New York, Flushing 11367.
Brain Res. 1992 Dec 4;597(2):331-8. doi: 10.1016/0006-8993(92)91490-6.
Supraspinal opioid analgesia is mediated in part by connections between the midbrain periaqueductal gray (PAG) and the ventral-medial medulla, including the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis (NRGC). A serotonergic synapse appears to participate in this pathway since methysergide microinjected into the NRM-NRGC significantly reduced morphine analgesia elicited from the PAG. The present study evaluated the role of specific serotonin receptor subtypes by pretreating rats with microinjections of either the 5HT2 antagonist, ritanserin or the 5HT3 antagonist, ICS205930, into the NRM-NRGC and examining their effects upon morphine (2.5 micrograms) analgesia elicited from the PAG. Mesencephalic morphine analgesia was significantly reduced following pretreatment with both ritanserin (0.25-2.5 micrograms) on the tail-flick (81%) and jump (65%) tests and ICS205930 (0.25-5 micrograms) on the tail-flick (91%) and jump (63%) tests. Neither ritanserin nor ICS205930 altered basal nociceptive thresholds. Medullary placements ventral or lateral to the NRM/NRGC failed to support these antagonistic effects. These data indicate that ventro-medial medullary 5HT2 and 5HT3 serotonergic receptors modulate the transmission of opioid pain-inhibitory signals from the PAG.
脊髓上阿片类镇痛作用部分是由中脑导水管周围灰质（PAG）与延髓腹内侧之间的联系介导的，包括中缝大核（NRM）和巨细胞网状核（NRGC）。由于向NRM - NRGC微量注射麦角新碱可显著降低由PAG引起的吗啡镇痛作用，因此5-羟色胺能突触似乎参与了这一途径。本研究通过向NRM - NRGC微量注射5HT2拮抗剂利坦色林或5HT3拮抗剂ICS205930预处理大鼠，并检查它们对由PAG引起的吗啡（2.5微克）镇痛作用的影响，来评估特定5-羟色胺受体亚型的作用。在甩尾试验（81%）和跳跃试验（65%）中，用利坦色林（0.25 - 2.5微克）预处理后，中脑吗啡镇痛作用显著降低；在甩尾试验（91%）和跳跃试验（63%）中，用ICS205930（0.25 - 5微克）预处理后，中脑吗啡镇痛作用也显著降低。利坦色林和ICS205930均未改变基础伤害性阈值。在NRM/NRGC腹侧或外侧的延髓部位注射未能证实这些拮抗作用。这些数据表明，延髓腹内侧的5HT2和5HT3 5-羟色胺能受体调节阿片类疼痛抑制信号从PAG的传递。
