Influence of a serotonin receptor antagonist, 5-HTP-DP-hex, on spinal and thalamic nociceptive neurons in rats.
Influence of a serotonin receptor antagonist, 5-HTP-DP-hex, on spinal and thalamic nociceptive neurons in rats.
复制标题
血清素受体拮抗剂 5-HTP-DP-hex 对大鼠脊髓和丘脑伤害性神经元的影响。
DOI：
10.1016/0014-4886(87)90214-7
复制
发表时间：
1987
影响因子：
5.3
通讯作者：
Wilchek,M
中科院分区：
文献类型：
--
作者：
Emmers,R;Tamir,H;Wilchek,M
用电生理方法研究了一种新合成的二肽（N-己酰-5-羟基色氨酸酰-5-羟基色氨酸酰胺，简称5-HTP-DP-hex）对大鼠的镇痛作用。在腹腔注射α-氯醛糖和乌拉坦后，准备对动物进行丘脑腹后外侧核的立体定位。利用钨微电极，通过响应坐骨神经的单脉冲刺激而发射的尖峰序列来识别核中的单个伤害性神经元。除了通常的短潜伏期尖峰，伤害性神经元在每次刺激后500 ms内以规则的间隔发射晚期尖峰。当棘波在刺激后时间直方图中累积时，短潜伏期棘波汇编成强度相关（I）峰。晚期棘波形成具有伤害性感受特征的间隔的模态相关（M）峰。颈动脉内注射5-HTP-DP-hex（1 mg/kg）可使Ipeak的延迟部分和第一个Mpeak升高。25分钟后，所有M峰均受到抑制。5-羟色氨酸（3.5mg/kg）可随时恢复控制记录，自然恢复2.5h后可恢复控制记录。由脊髓丘脑束的单脉冲刺激引起的丘脑伤害性神经元的反应被修改5-HTP-DP-六角以类似的方式，除了没有观察到的活动峰的升高。如前所述，延迟I峰和M1峰的升高分别表明A-δ和C纤维的输入增加。增加的输入降低了反应阈值，并可能代表痛觉过敏。M峰的抑制可能是由于丘脑水平的伤害感受系统中正反馈回路的功能改变所致，并可能代表镇痛。纳洛酮、麦角新碱和酮色林对反应直方图无显著影响。这些发现表明，5-HTP-DP-hex是一种已知的5-羟色胺受体拮抗剂，其作用靶向于非常特异的受体，从而干扰脊髓内和丘脑水平上的特定突触活动。
The antinociceptive properties of a new synthetic dipeptide (N-hexanoyl-5-hydroxytryptophyl-5-hydroxytryptophan amide, or 5-HTP-DP-hex) were studied in rats by an electrophysiological method. After an i.p. injection of α-chloralose and urethane, the animals were prepared for stereotaxic approach to the nucleus ventralis posterolateralis of the thalamus. With tungsten microelectrodes, individual nociceptive neurons in the nucleus were identified by the sequence of spikes emitted in response to single-pulse stimulation of the sciatic nerve. In addition to the usual short-latency spikes, a nociceptive neuron fired late spikes at regular intervals within 500 ms following each stimulus. When the spikes were accumulated in poststimulus time histograms, the short-latency spikes compiled an intensity-related (I) peak. The late spikes formed modality-related (M) peaks with spacing characteristic of nociception. Intracarotid infusion of 5-HTP-DP-hex (1 mg/kg) elevated the delayed portion of theIpeak and the firstMpeak. This effect was followed in 25 min by suppression of allMpeaks. The control record could be reinstated at any time by 5-hydroxytryptophan (3.5 mg/kg), or by natural recovery in 2.5 h. Responses evoked from a thalamic nociceptive neuron by single-pulse stimulation of the spinothalamic tract were modified by 5-HTP-DP-hex in a similar manner, except that no elevation of the activity peaks was observed. As shown previously, elevation of the delayedIpeak andM1indicated an increased input of A-δ and C fibers, respectively. The increased input lowers the response threshold and may represent hyperalgesia. Suppression of theMpeaks may result from altered function of the positive feedback loop in the nociceptive system at the thalamic level, and may represent analgesia. Naloxone, methysergide, as well as ketanserin had no significant effect on the response histograms. These findings suggested that 5-HTP-DP-hex, a known serotonin receptor antagonist, targeted its action on very specific receptors, and thus interfered with particular synaptic activity within the spinal cord and on the thalamic level.