Motor cortex stimulation (MCS) is an effective therapy for refractory neuropathic pain. MCS increases the nociceptive threshold in healthy rats via endogenous opioids, inhibiting thalamic nuclei and activating the periaqueductal gray. It remains unclear how the motor cortex induces top-down modulation of pain in the absence of persistent pain. Here, we investigated the main nuclei involved in the descending analgesic pathways and the spinal nociceptive neurons in rats that underwent one session of MCS and were evaluated with the paw pressure nociceptive test. The pattern of neuronal activation in the dorsal raphe nucleus (DRN), nucleus raphe magnus (NRM), locus coeruleus (LC), and dorsal horn of the spinal cord (DHSC) was assessed by immunoreactivity (IR) for Egr-1 (a marker of activated neuronal nuclei). IR for serotonin (5HT) in the DRN and NRM, tyrosine hydroxylase (TH) in the LC, and substance P (SP) and enkephalin (ENK) in the DHSC was also evaluated. MCS increased the nociceptive threshold of the animals; this increase was accompanied by activation of the NRM, while DRN activation was unchanged. However, cortical stimulation induced an increase in 5HT-IR in both serotonergic nuclei. MCS did not change the activation pattern or TH-IR in the LC, and it inhibited neuronal activation in the DHSC without altering SP or ENK-IR. Taken together, our results suggest that MCS induces the activation of serotonergic nuclei as well as the inhibition of spinal neurons, and such effects may contribute to the elevation of the nociceptive threshold in healthy rats. These results allow a better understanding of the circuitry involved in the antinociceptive top-down effect induced by MCS under basal conditions, reinforcing the role of primary motor cortex in pain control.

中文翻译：

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运动皮层和疼痛控制：探索健康意识大鼠的递减镇痛途径和脊髓伤害感受性神经元。

运动皮质刺激（MCS）是治疗难治性神经性疼痛的有效疗法。MCS通过内源性阿片类药物增加健康大鼠的伤害感受性阈值，抑制丘脑核并激活导水管周围的灰色。尚不清楚在没有持续性疼痛的情况下，运动皮层如何诱发自上而下的疼痛调节。在这里，我们调查了经历了一次MCS的大鼠的下行镇痛途径中涉及的主要细胞核和脊髓伤害感受性神经元，并用爪压伤害感受试验进行了评估。通过免疫反应性（IR）评估Egr-1（a）的背缝核（DRN），缝核大核（NRM），蓝斑轨迹（LCSC）和脊髓背角（DHSC）中的神经元激活模式。激活的神经元核标记）。DRN和NRM中5-羟色胺（5HT）的IR，还评估了LC中的酪氨酸羟化酶（TH），DHSC中的物质P（SP）和脑啡肽（ENK）。MCS增加了动物的伤害阈值；这种增加伴随着NRM的激活，而DRN的激活没有改变。然而，皮层刺激诱导了两个血清素能核中5HT-1R的增加。MCS不会改变LC中的激活模式或TH-IR，它在不改变SP或ENK-IR的情况下抑制了DHSC中的神经元激活。两者合计，我们的结果表明，MCS诱导了血清素能神经核的激活以及对脊髓神经元的抑制，并且这种作用可能有助于健康大鼠的伤害感受性阈值的升高。