Karlsson Gudbjorn A, Chaitoff Kevin A, Hossain Shamma, Böhlke Mark, Maher Timothy J, Ally Ahmmed
Emergency Department, Inland Hospital, Waterville, ME 04910, USA.
Brain Res. 2007 Apr 27;1143:150-60. doi: 10.1016/j.brainres.2007.01.101. Epub 2007 Feb 1.
Nitric oxide (NO) within the dorsal periaqueductal gray matter (dPAG) attenuated cardiovascular responses and changes in the concentrations of glutamate during both mechanical and thermal nociceptive stimulation [Ishide, T., Amer, A., Maher, T.J., Ally, A., 2005. Nitric oxide within periaqueductal gray modulates glutamatergic neurotransmission and cardiovascular responses during mechanical and thermal stimuli. Neurosci. Res. 51, 93-103]. Nitric oxide is synthesized from l-arginine via the enzyme, NO synthase (NOS), which exists in 3 isoforms: endothelial (eNOS), neuronal (nNOS), and inducible (iNOS). In this study, we examined the role of nNOS within the dPAG on cardiovascular responses and extracellular glutamate and GABA concentrations during mechanical and thermal nociception in anesthetized rats. The noxious mechanical stimulus was applied by a bilateral hindpaw pinch for 5 s that increased mean arterial pressure (MAP) and heart rate (HR) by 24+/-4 mm Hg and 41+/-7 bpm, respectively (n=10). Extracellular glutamate levels within the dPAG increased by 10.7+/-1.3 ng/mul while GABA concentrations decreased by 1.9+/-0.5 ng/microl. Bilateral microdialysis of a selective nNOS antagonist, 1-(2-trifluoromethylphenyl)-imidazole (TRIM; 10.0 microM), into the dPAG had no effect on MAP, HR, glutamate and GABA values (P>0.05) during a mechanical stimulation. In a separate set of experiments, a noxious thermal stimulus was generated by immersing the metatarsus of a hindpaw in a water-bath at 52 degrees C for 5 s (n=10). Glutamate, MAP, and HR increased by 14.6+/-2 ng/microl, 45+/-6 mm Hg, and 47+/-7 bpm, while GABA decreased by 2.1+/-0.6 ng/microl. Administration of TRIM into the dPAG significantly enhanced the cardiovascular responses and glutamate increases (P<0.05) but further attenuated GABA changes (P<0.05) during subsequent thermal nociception. These results demonstrate that nNOS within the dPAG plays a differential role in modulating cardiovascular responses and glutamatergic/GABAergic neurotransmission during thermal and mechanical nociception.
中脑导水管周围灰质背侧（dPAG）中的一氧化氮（NO）在机械性和热痛觉刺激过程中可减弱心血管反应以及谷氨酸浓度的变化[石出，T.，阿迈尔，A.，马赫，T.J.，艾利，A.，2005年。中脑导水管周围灰质中的一氧化氮在机械性和热刺激过程中调节谷氨酸能神经传递和心血管反应。神经科学研究。51，93 - 103]。一氧化氮由L - 精氨酸通过一氧化氮合酶（NOS）合成，NOS存在三种同工型：内皮型（eNOS）、神经元型（nNOS）和诱导型（iNOS）。在本研究中，我们研究了麻醉大鼠在机械性和热痛觉感受过程中，dPAG内nNOS对心血管反应以及细胞外谷氨酸和γ - 氨基丁酸（GABA）浓度的作用。通过双侧后爪夹捏5秒施加有害机械刺激，平均动脉压（MAP）和心率（HR）分别升高24±4 mmHg和41±7次/分钟（n = 10）。dPAG内细胞外谷氨酸水平升高10.7±1.3 ng/μl，而GABA浓度降低1.9±0.5 ng/μl。将选择性nNOS拮抗剂1 - （2 - 三氟甲基苯基） - 咪唑（TRIM；10.0 μM）双侧微透析到dPAG中，在机械刺激期间对MAP、HR、谷氨酸和GABA值无影响（P>0.05）。在另一组实验中，通过将后爪跖骨浸入52℃水浴中5秒产生有害热刺激（n = 10）。谷氨酸、MAP和HR分别升高14.6±2 ng/μl、45±6 mmHg和47±7次/分钟，而GABA降低2.1±0.6 ng/μl。在随后的热痛觉感受期间，将TRIM注入dPAG显著增强了心血管反应和谷氨酸的增加（P<0.05），但进一步减弱了GABA的变化（P<0.05）。这些结果表明，dPAG内的nNOS在热痛觉和机械痛觉感受过程中，对调节心血管反应以及谷氨酸能/γ - 氨基丁酸能神经传递发挥不同作用。
