From the Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom (A.H.D., R.P.) Department of Pharmacology, University of Arizona, Tucson, Arizona (E.N., F.P.) the Department of Pharmacology and Therapeutics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom (K.B.).
Anesthesiology. 2020 Apr;132(4):881-894. doi: 10.1097/ALN.0000000000003120.
The anterior cingulate cortex and central nucleus of the amygdala connect widely with brainstem nuclei involved in descending modulation, including the rostral ventromedial medulla. Endogenous opioids in these circuits participate in pain modulation. The hypothesis was that a differential opioidergic role for the brain nuclei listed in regulation of spinal neuronal responses because separable effects on pain behaviors in awake animals were previously observed.
This study utilized in vivo electrophysiology to determine the effects of morphine microinjection into the anterior cingulate cortex, right or left central nucleus of the amygdala, or the rostral ventromedial medulla on spinal wide dynamic range neuronal responses in isoflurane-anesthetized, male Sprague-Dawley rats. Ongoing activity in the ventrobasal thalamus was also measured. In total, 33 spinal nerve ligated and 26 control age- and weight-matched control rats were used.
Brainstem morphine reduced neuronal firing to 60-g von Frey stimulation in control rats (to 65 ± 12% of control response (means ± 95% CI), P < 0.001) with a greater inhibition in neuropathic rats (to 53 ± 17% of control response, P < 0.001). Contrasting anterior cingulate cortex morphine had only marginal modulatory effects on spinal neuronal responses with limited variance in effect between control and neuropathic rats. The inhibitory effects of morphine in the central nucleus of the amygdala were dependent on pain state and laterality; only right-side morphine reduced neuronal firing to 60-g stimulation in neuropathic rats (to 65 ± 14% of control response, P = 0.001). In addition, in neuropathic rats elevated ongoing neuronal activity in the ventral posterolateral thalamus was not inhibited by anterior cingulate cortex morphine, in contrast to evoked responses.
Cumulatively the data support opioid modulation of evoked responses predominately through a lateralized output from the right amygdala, as well as from the brainstem that is enhanced in injured conditions. Minimal modulation of dorsal horn responses was observed after anterior cingulate cortex opioid administration regardless of injury state.
前扣带皮层和杏仁核中央核与脑干核广泛连接，参与下行调节，包括吻侧腹内侧髓质。这些回路中的内源性阿片参与疼痛调节。假设列出的脑核在调节脊髓神经元反应中的阿片能作用不同，因为先前观察到对清醒动物疼痛行为有可分离的影响。
本研究利用体内电生理学方法，确定在异氟烷麻醉的雄性 Sprague-Dawley 大鼠中，将吗啡微注射到前扣带皮层、右侧或左侧杏仁核中央核或吻侧腹内侧髓质中对脊髓宽动态范围神经元反应的影响。还测量了腹侧基底节的持续活动。总共使用了 33 只脊髓神经结扎和 26 只年龄和体重匹配的对照大鼠。
脑桥吗啡降低了对照组大鼠对 60-g von Frey 刺激的神经元放电（降至对照组反应的 65±12%（平均值±95%置信区间），P<0.001），而神经病理性大鼠的抑制作用更大（降至对照组反应的 53±17%，P<0.001）。前扣带皮层吗啡对脊髓神经元反应仅有轻微的调节作用，对对照组和神经病理性大鼠的影响差异有限。杏仁核中央核吗啡的抑制作用取决于疼痛状态和侧位；只有右侧吗啡降低了神经病理性大鼠对 60-g 刺激的神经元放电（降至对照组反应的 65±14%，P=0.001）。此外，在神经病理性大鼠中，背侧丘脑腹后外侧核的持续神经元活动升高，前扣带皮层吗啡不能抑制，而对诱发电应则可以抑制。
累积数据支持阿片类药物通过来自右侧杏仁核的偏侧输出以及在损伤条件下增强的脑干对诱发电应的调节，而对背角反应的调节作用很小。无论损伤状态如何，前扣带皮层阿片类药物给药后观察到对背角反应的调节作用最小。
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