1. Academic Validation
  2. Ropivacaine-induced seizures evoked pain sensitization in rats: Participation of 5-HT/5-HT3R

Ropivacaine-induced seizures evoked pain sensitization in rats: Participation of 5-HT/5-HT3R

  • Neurotoxicology. 2022 Oct 6;S0161-813X(22)00156-5. doi: 10.1016/j.neuro.2022.10.001.
Chen-Long Yang 1 Jun-Jie Jing 2 Si-Yin Fu 1 Yu-Ling Zhong 1 Xiu-Zhu Su 1 Zhong-Mou Shi 1 Xiao-Zhi Wu 3 Fei Yang 4 Guo-Zhong Chen 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology and Perioperative Medicine, Clinical Medical College, (900th Hospital of the Joint Logistic Support Force), Fujian Medical University, Fuzhou Fujian, P.R. China.
  • 2 Department of Neurosurgery, Fujian Children's Hospital,College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, P.R. China.
  • 3 Department of Anesthesiology and Perioperative Medicine, Clinical Medical College, (900th Hospital of the Joint Logistic Support Force), Fujian Medical University, Fuzhou Fujian, P.R. China. Electronic address: www7410@sohu.com.
  • 4 Department of Anesthesiology and Perioperative Medicine, Clinical Medical College, (900th Hospital of the Joint Logistic Support Force), Fujian Medical University, Fuzhou Fujian, P.R. China; Pain Research Institute, Fujian Medical University, Fuzhou, Fujian, P.R. China. Electronic address: yangfeimedbrain@outlook.com.
  • 5 Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, P.R. China. Electronic address: cgzssq2000@sina.com.
Abstract

Due to the increasing use of local anesthetic techniques in various healthcare settings, local anesthetic toxicity still occurs. Seizures are the most common symptom of local anesthetic toxicity. The relationship between local anesthetic-induced seizures and the sensation of pain has not been established till now. Here, we assessed the development of pain hypersensitivity after ropivacaine-induced seizures (RIS) and the influence of RIS on incision-induced postsurgical pain and formalin-induced acute inflammatory pain. In addition, the involvement of spinal 5-HT/5-HT3R in RIS-induced pain sensitization was investigated. According to a sequential exploratory experimental strategy, we first calculated the 50% seizure dosage of ropivacaine to be 42.66mg/kg (95% confidence interval: 40.19-45.28mg/kg). We showed that RIS induced significant bilateral mechanical pain hypersensitivity that lasted around 5 days, accompanied by an increase in spinal 5-HT. Moreover, RIS considerably protracted postsurgical pain and enhanced formalin-induced spontaneous flinching in the second phase. Depletion of spinal 5-HT with intrathecal injection of 5,7-dihydroxytryptamine (5,7-DHT) reduced RIS-induced pain hypersensitivity and prevented the prolonging of postsurgical pain following RIS. Likewise, blocking spinal 5-HT3R by intrathecal administration of ondansetron reversed RIS-induced pain hypersensitivity and attenuated the pronociception of RIS in the formalin test. Our findings revealed that acute RIS led to pain hypersensitivity and had pronociceptive effects on incision-induced postsurgical pain and formalin-induced acute inflammatory pain. Moreover, our data implied that RIS-induced pain sensitization depends on spinal 5-HT/5-HT3R signaling. Thus, targeting the descending serotonergic facilitation system should be an important element of the precise treatment for local anesthetic toxicity.

Keywords

5-HT; 5-HT(3) receptor; local anesthetic toxicity; pain; ropivacaine; seizures.

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