Antinociceptive effects of nefopam modulating serotonergic, adrenergic, and glutamatergic neurotransmission in the spinal cord. (13th July 2020)

• Record Type: Journal Article
• Authors: Chae, Joo Wung; Kang, Dong Ho; Li, Yaqun; Kim, Seung Hoon; Lee, Hyung Gon; Choi, Jeong Il; Yoon, Myung Ha; Kim, Woong Mo
• Is Part Of: Neuroscience letters. Volume 731(2020)
• Publication Date: 2020-07-13
• Subjects: Glutamate -- Microdialysis -- Nefopam -- Norepinephrine -- Serotonin; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2020.135057
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Intrathecal nefopam effectively attenuated formalin-induced pain behavior. Intrathecal nefopam inhibited the reuptake of 5-HT and NE and reduced glutamate release after formalin injection. The blockade of serotonergic, adrenergic, or group III metabotropic glutamate receptors partially reversed the analgesic effects of nefopam. Abstract: The present study investigated the effects of intrathecal nefopam on the pain behavior and on the extracellular levels of serotonin (5-HT), norepinephrine (NE), and glutamate in the spinal cord, in a rat model of pain induced by formalin. Nefopam was intrathecally administered 10 min prior to the formalin test to assess its antinociceptive effects. In another cohorts of animals, dihydroergocristine, yohimbine, or (RS)-α-Methylserine-O-phosphate (MSOP), a serotonergic, α-2 adrenergic receptor, or group III metabotropic glutamate receptor antagonist, respectively, were administered prior to the application of nefopam in the formalin test. Microdialysis studies were conducted to measure the extracellular levels of 5-HT, NE, and glutamate in the spinal cord following nefopam administration. Intrathecal nefopam reduced formalin-induced behavior in both phases of the test. The blockade of serotonergic or adrenergic receptors partially reversed the analgesic effects of nefopam in the first phase of the formalin test whereas MSOP reversed these effects in both phases. The microdialysis results revealed that intrathecal nefopam significantly increased 5-HT and NE levels and attenuated the formalin-induced release of glutamate in the spinal cord. Thus, the present data suggest that the increase in the extracellular levels of 5-HT and NE, and reductions in glutamate release in the spinal cord, may have contributed to the analgesic effects of nefopam.