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Dexmedetomidine Relieves Acute Inflammatory Visceral Pain in Rats through the ERK Pathway, Toll-Like Receptor Signaling, and TRPV1 Channel

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Abstract

Dexmedetomidine (DEX) is a highly selective α2 adrenergic receptor agonist. In this study, we aimed to characterize the antinociceptive effects of DEX in acute inflammatory visceral pain (AIVP) induced by acetic acid in rats and to evaluate whether antinociception was regulated by the extracellular signal-regulated protein kinase (ERK) pathway, Toll-like receptor (TLR) signaling, and transient receptor potential (TRP) channel. Acetic acid was administered to 30 male rats with or without DEX. Rats were divided into six groups, as follows: control, disease (received no treatment before acetic acid administration), vehicle-treated, low-dose DEX (lDEX), medium-dose DEX (mDEX), and high-dose DEX (hDEX)-treated groups. Thermal withdrawal latency (TWL), mechanical withdrawal threshold (MWT), and abdominal withdrawal reflex (AWR) were measured to assess pain. We detected electromyographic (EGM) responses in the rectus abdominis muscle and measured the average arterial blood pressure. Levels of interleukin 1 (IL-1), IL-2, and IL-6 in the serum, as well as tumor necrosis factor α (TNF-α) and prostaglandin E2 (PGE2) in the peritoneal fluid, were measured by ELISA. The expression levels of phospho(p)CREB, pERK1/2, pMEK1, and TRP cation channel subfamily V member 1 (TRPV1), as well as the activation state of TLR4, were determined in the spinal cord of rats by real-time polymerase chain reaction and western blot analysis. TWL and MWT scores were elevated (P < 0.05) in the hDEX and mDEX groups, whereas AWR scores decreased (P < 0.01), compared to those in the disease group. The medium and high doses of DEX suppressed IL-1, IL-6, TNF-α, and PGE2 release, and increased IL-2 release. In addition, protein and mRNA levels of MEK, ERK, and CREB were reduced in the mDEX and hDEX groups. Moreover, TLR4 and its downstream target, nuclear factor kappa B, along with calcitonin gene-related peptide release through the TRPV1 channel, were suppressed by mDEX and hDEX treatment. Taken together, our results suggest that DEX might exert an antinociceptive effect in AIVP in rats through the MEK/ERK pathway, TLR signaling, and TRPV1 channel, resulting in suppression of visceral hypersensitivity.

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Authors and Affiliations

  1. Department of anesthesiology, First Hospital of Lanzhou University, No. 1 Donggang Xi Road , Chengguan District, Lanzhou, 730000, Gansu, China

    Yatao Liu, Xiaoqing Wang, Zhanhai Wan, Yongqiang Liu & Yufang Leng

  2. Department of Pathology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China

    Wei Liu

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  1. Yatao Liu
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  2. Wei Liu
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  3. Xiaoqing Wang
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Correspondence to Yufang Leng.

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Liu, Y., Liu, W., Wang, X. et al. Dexmedetomidine Relieves Acute Inflammatory Visceral Pain in Rats through the ERK Pathway, Toll-Like Receptor Signaling, and TRPV1 Channel. J Mol Neurosci 66, 279–290 (2018). https://doi.org/10.1007/s12031-018-1172-5

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  • DOI: https://doi.org/10.1007/s12031-018-1172-5

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