Karlsson Gudbjorn A, Preuss Charles V, Chaitoff Kevin A, Maher Timothy J, Ally Ahmmed
Department of Pharmaceutical Sciences, Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, FL 33416, and Emergency Department, Inland Hospital, Waterville, ME 04910, USA.
Neurosci Res. 2006 Jul;55(3):316-26. doi: 10.1016/j.neures.2006.04.002. Epub 2006 May 8.
We have previously reported that AMPA-receptor blockade within the rostral ventrolateral medulla (RVLM) attenuates cardiovascular responses and extracellular concentrations of glutamate during mechanical, but not during thermal stimulation [Gray, T., Lewis III, E., Maher, T.J., Ally, A., 2001. AMPA-receptor blockade within the RVLM modulates cardiovascular responses via glutamate during peripheral stimuli. Pharmacol. Res. 43, 47-54]. In this study, we examined the role of NMDA-receptor blockade within the RVLM on cardiovascular responses and release of biogenic monoamines (serotonin [5HT], dopamine [DA], and norepinephrine [NE]) during both mechanical and thermal nociception using anesthetized Sprague-Dawley rats. Both mechanical and thermal stimulation have been shown to activate peripheral Adelta and C-fiber polymodal nociceptors. Noxious mechanical stimuli were induced by applying a pinch to alternate hindpaw for 5s while the noxious thermal stimuli involved immersion of the metatarsus of alternate hindpaw in a water bath at a temperature of 52 degrees C for 5 s. Mechanical stimulation increased mean arterial pressure (MAP), heart rate (HR), extracellular fluid 5HT, and DA concentrations (n=10). However, extracellular levels of NE were decreased within the RVLM. Furthermore, NMDA-receptor blockade with a competitive antagonist, AP-7 (200 nM), within the RVLM attenuated the cardiovascular responses and changes in 5HT and DA, but had no effect on NE levels. The thermal stimulation elicited similar increases in MAP and HR, however, extracellular levels of 5HT or DA did not change. Concentrations of NE were decreased during a thermal stimulation similar to the levels observed following mechanical stimuli. In contrast to mechanical stimuli, bilateral administration of AP-7 (200-1 mM) into the RVLM had no effect on cardiovascular responses, 5HT, DA or NE concentrations during a thermal stimulation. These results show that NMDA receptors within the RVLM most likely play a role in modulating cardiovascular responses by altering 5HT and DA concentrations within the RVLM during mechanical but not thermal nociception. Overall, the present study delineates the NMDA-receptor mediated central integrative mechanisms within the RVLM that coordinate processing of sensory impulses arising from peripheral noxious stimulation.
我们之前报道过，在延髓头端腹外侧区（RVLM）内阻断AMPA受体可减弱机械刺激而非热刺激期间的心血管反应及细胞外谷氨酸浓度[格雷，T.，刘易斯三世，E.，马赫，T.J.，艾利，A.，2001年。RVLM内的AMPA受体阻断在周围刺激期间通过谷氨酸调节心血管反应。药理学研究。43，47 - 54]。在本研究中，我们使用麻醉的Sprague - Dawley大鼠，研究了RVLM内NMDA受体阻断在机械性和热伤害性感受期间对心血管反应及生物源性单胺（5 - 羟色胺[5HT]、多巴胺[DA]和去甲肾上腺素[NE]）释放的作用。机械性和热刺激均已被证明可激活外周Aδ和C纤维多模式伤害感受器。通过交替捏后爪5秒诱导有害机械刺激，而有害热刺激则是将交替后爪的跖骨浸入5℃的水浴中5秒。机械刺激可增加平均动脉压（MAP）、心率（HR）、细胞外液5HT和DA浓度（n = 10）。然而，RVLM内NE的细胞外水平降低。此外，在RVLM内用竞争性拮抗剂AP - 7（200 nM）阻断NMDA受体可减弱心血管反应以及5HT和DA浓度的变化，但对NE水平无影响。热刺激引起类似的MAP和HR升高，然而，5HT或DA的细胞外水平未发生变化。热刺激期间NE浓度降低，类似于机械刺激后观察到的水平。与机械刺激不同，向RVLM双侧注射AP - 7（200 - 1 mM）对热刺激期间的心血管反应、5HT、DA或NE浓度无影响。这些结果表明，RVLM内的NMDA受体很可能在机械性而非热伤害性感受期间通过改变RVLM内的5HT和DA浓度来调节心血管反应。总体而言，本研究描绘了RVLM内NMDA受体介导的中枢整合机制，该机制协调来自外周有害刺激的感觉冲动的处理。
