后岛叶皮质颗粒下层的皮质神经刺激和N-甲基-D-天冬氨酸谷氨酸能受体激活可调节慢性神经性疼痛。
Cortical Neurostimulation and N-Methyl-D-Aspartate Glutamatergic Receptor Activation in the Dysgranular Layer of the Posterior Insular Cortex Modulate Chronic Neuropathic Pain.
作者信息
Martins Pereira Renata Cristina, Medeiros Priscila, Coimbra Norberto Cysne, Machado Hélio Rubens, de Freitas Renato Leonardo
机构信息
Multi-User Center of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Laboratory of Neurosciences of Pain & Emotions, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Brain Protection Laboratory in Childhood, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Multi-User Center of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Laboratory of Neurosciences of Pain & Emotions, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Neurosciences and Behavioral Sciences. Department of Pharmacology. Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Federal University of São Carlos Pain Clinic, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
出版信息
Neuromodulation. 2023 Dec;26(8):1622-1636. doi: 10.1016/j.neurom.2022.05.009. Epub 2022 Aug 31.
BACKGROUND AND AIMS
The dysgranula parts of the posterior insular cortex (PIC) stimulation (PICS) has been investigated as a new putative cortical target for nonpharmacologic therapies in patients with chronic and neuropathic pain (NP). This work investigates the neural bases of insula neurostimulation-induced antinociception and glutamatergic neurochemical mechanisms recruited by the PICS in animals with neuropathy.
MATERIALS AND METHODS
Male Wistar rats were submitted to the von Frey and acetone tests to assess mechanical and cold allodynia after 21 days of chronic constriction injury (CCI) of the sciatic nerve or Sham procedure ("false operated"). Either the Cascade Blue 3000 MW lysine-fixable dextran (CBD) or the biotinylated dextran amine 3000 MW (BDA) neural tract tracer was microinjected into the PIC. The electrical PICS was performed at a low frequency (20 μA, 100 Hz) for 15 seconds by a deep brain stimulation device. PIC N-methyl-D-aspartate (NMDA) receptors (NMDAR) blockade with the selective antagonist LY235959 (at 2, 4, and 8 nmol/200 nL) followed by PICS was investigated in rats with CCI.
RESULTS
PIC sends projections to the caudal pontine reticular nucleus, alpha part of the parvicellular reticular nucleus, dorsomedial tegmental area, and secondary somatosensory cortex (S). PICS decreased both mechanical and cold allodynia in rats with chronic NP. Blockade of NMDAR in the PIC with LY235959 at 8 nmol attenuated PICS-produced antinociception.
CONCLUSION
Neuroanatomic projections from the PIC to pontine reticular nuclei and S may contribute to chronic NP signaling. PICS attenuates the chronic NP, and the NMDA glutamatergic system in the PIC may be involved in PICS-induced antinociception in rodents with NP conditions.
背景与目的
后岛叶皮质（PIC）刺激（PICS）的颗粒异常部分已被研究作为慢性和神经性疼痛（NP）患者非药物治疗的一种新的假定皮质靶点。本研究探讨在患有神经病变的动物中，岛叶神经刺激诱导的抗伤害感受的神经基础以及PICS募集的谷氨酸能神经化学机制。
材料与方法
雄性Wistar大鼠在坐骨神经慢性缩窄损伤（CCI）21天后或假手术（“假手术”）后，接受von Frey和丙酮试验以评估机械性和冷觉异常性疼痛。将级联蓝3000 MW赖氨酸固定葡聚糖（CBD）或生物素化葡聚糖胺3000 MW（BDA）神经示踪剂微量注射到PIC中。通过深部脑刺激装置以低频（20 μA，100 Hz）进行15秒的电PICS。在患有CCI的大鼠中，研究用选择性拮抗剂LY235959（2、4和8 nmol/200 nL）阻断PIC中的N-甲基-D-天冬氨酸（NMDA）受体（NMDAR）后再进行PICS的情况。
结果
PIC向尾侧脑桥网状核、小细胞网状核α部分、背内侧被盖区和次级体感皮层（S）发出投射。PICS减轻了慢性NP大鼠的机械性和冷觉异常性疼痛。用8 nmol的LY235959阻断PIC中的NMDAR减弱了PICS产生的抗伤害感受。
结论
从PIC到脑桥网状核和S的神经解剖投射可能有助于慢性NP信号传导。PICS减轻慢性NP，并且PIC中的NMDA谷氨酸能系统可能参与NP状态啮齿动物中PICS诱导的抗伤害感受。
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