From the Laboratoire d'Anesthésie, Paris-Saclay University and INSERM U1195 Faculté de Médecine de Bicêtre, Le Kremlin-Bicêtre, France.
Department of Anesthesiology and Intensive Care Medicine, Hôpital Bichat, Hôpitaux Universitaires Paris-Nord, APHP.
Anesth Analg. 2021 Nov 1;133(5):1311-1320. doi: 10.1213/ANE.0000000000005697.
Visceral and parietal peritoneum layers have different sensory innervations. Most visceral peritoneum sensory information is conveyed via the vagus nerve to the nucleus of the solitary tract (NTS). We already showed in animal models that intramuscular (i.m.) injection of local anesthetics decreases acute somatic and visceral pain and general inflammation induced by aseptic peritonitis. The goal of the study was to compare the effects of parietal block, i.m. bupivacaine, and vagotomy on spinal cord and NTS stimulation induced by a chemical peritonitis.
We induced peritonitis in rats using carrageenan and measured cellular activation in spinal cord and NTS under the following conditions, that is, a parietal nerve block with bupivacaine, a chemical right vagotomy, and i.m. microspheres loaded with bupivacaine. Proto-oncogene c-Fos (c-Fos), cluster of differentiation protein 11b (CD11b), and tumor necrosis factor alpha (TNF-α) expression in cord and NTS were studied.
c-Fos activation in the cord was inhibited by nerve block 2 hours after peritoneal insult. Vagotomy and i.m. bupivacaine similarly inhibited c-Fos activation in NTS. Forty-eight hours after peritoneal insult, the number of cells expressing CD11b significantly increased in the cord (P = .010). The median difference in the effect of peritonitis compared to control was 30 cells (CI95, 13.5-55). TNF-α colocalized with CD11b. Vagotomy inhibited this microglial activation in the NTS, but not in the cord. This activation was inhibited by i.m. bupivacaine both in cord and in NTS. The median difference in the effect of i.m. bupivacaine added to peritonitis was 29 cells (80% increase) in the cord and 18 cells (75% increase) in the NTS. Our study underlines the role of the vagus nerve in the transmission of an acute visceral pain message and confirmed that systemic bupivacaine prevents noxious stimuli by inhibiting c-Fos and microglia activation.
In rats receiving intraperitoneal carrageenan, i.m. bupivacaine similarly inhibited c-Fos and microglial activation both in cord and in the NTS. Vagal block inhibited activation only in the NTS. Our study underlines the role of the vagus nerve in the transmission of an acute visceral pain message and confirmed that systemic bupivacaine prevents noxious stimuli. This emphasizes the effects of systemic local anesthetics on inflammation and visceral pain.
内脏和壁腹膜层具有不同的感觉神经支配。大多数内脏腹膜感觉信息通过迷走神经传递到孤束核（NTS）。我们已经在动物模型中表明，肌肉内（i.m.）注射局部麻醉剂可减少由无菌性腹膜炎引起的急性躯体和内脏疼痛以及全身炎症。本研究的目的是比较壁层神经阻滞、i.m.布比卡因和迷走神经切断术对化学性腹膜炎引起的脊髓和 NTS 刺激的影响。
我们使用角叉菜胶在大鼠中诱导腹膜炎，并在以下情况下测量脊髓和 NTS 中的细胞激活情况，即布比卡因的壁层神经阻滞、右侧化学性迷走神经切断术和负载布比卡因的 i.m.微球。研究了脊髓和 NTS 中原癌基因 c-Fos（c-Fos）、分化簇蛋白 11b（CD11b）和肿瘤坏死因子-α（TNF-α）的表达。
腹膜损伤后 2 小时，神经阻滞可抑制脊髓内 c-Fos 的激活。迷走神经切断术和 i.m.布比卡因同样抑制 NTS 中 c-Fos 的激活。腹膜损伤后 48 小时，脊髓中表达 CD11b 的细胞数量显著增加（P=0.010）。与对照组相比，腹膜炎的中位差异为 30 个细胞（CI95，13.5-55）。TNF-α与 CD11b 共定位。迷走神经切断术抑制了 NTS 中的小胶质细胞激活，但在脊髓中没有。i.m.布比卡因在脊髓和 NTS 中均抑制了这种小胶质细胞的激活。在加入腹膜炎的 i.m.布比卡因的作用中，脊髓中的中位差异为 29 个细胞（增加 80%），NTS 中的中位差异为 18 个细胞（增加 75%）。我们的研究强调了迷走神经在传递急性内脏痛觉信息中的作用，并证实了全身布比卡因通过抑制 c-Fos 和小胶质细胞激活来预防有害刺激。
在接受腹腔内角叉菜胶的大鼠中，i.m.布比卡因同样抑制了脊髓和 NTS 中的 c-Fos 和小胶质细胞激活。迷走神经阻断仅在 NTS 中抑制激活。我们的研究强调了迷走神经在传递急性内脏痛觉信息中的作用，并证实了全身布比卡因可以预防有害刺激。这强调了全身局部麻醉剂对炎症和内脏疼痛的影响。
