期刊
NEUROCHEMISTRY INTERNATIONAL
卷 131, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2019.104562
关键词
Antinociception; Pronociception; Formalin test; 5-HT6 receptor; Ventrolateral orbital cortex
资金
- National Natural Science Foundation of China [81971792, 81870886, 81901920]
- Opening Project of the Key Laboratory of Forensic Medicine and Science (Xi'an Jiaotong University)
- National Health Commission of China [2019FYXH003]
- New Researchers' Supporting Program of Xi'an Jiaotong University [xxj022019011]
Recent studies have shown the 5-HT6 receptors are expressed in regions which are important in pain processing such as the cortex, amygdala, thalamus, PAG, spinal cord and dorsal root ganglia (DRG), suggesting a putative role of 5-HT6 receptors in pain modulation. The ventrolateral orbital cortex (VLO) is part of an endogenous analgesic system, consisting of the spinal cord - thalamic nucleus submedius (Sm) - VLO - periaqueductal gray (PAG) - spinal cord loop. The present study assessed the possible role of 5-HT(6 )receptors in the VLO in formalin-induced inflammatory pain model. Firstly we found that microinjection of selective 5-HT6 receptor agonists EMD-386088 (5 mu g in 0.5 mu l) and WAY-208466 (8 mu g in 0.5 mu l) both augmented 5% formalin-induced nociceptive behavior. Microinjection of selective 5-HT6 receptor antagonist SB-258585 (1,2 and 4 mu g in 0.5 mu l) significantly reduced formalin-induced flinching. Besides, the pronociceptive effects of EMD-386088 and WAY-208466 were dramatically reduced by SB-258585, implicating 5-HT6 receptor mechanisms in mediating these responses. In addition, the pronociceptive effect of EMD-386088 was also prevented by the adenylate cyclase (AC) inhibitor SQ-22536 (2 nmol in 0.5 mu l) and the protein kinase A (PICA) inhibitor H89 (10 nmol in 0.5 mu l), respectively. We further confirmed the above results with quantification of spinal c-fos expression. Taken together, our results suggested that 5-HT6 receptors play a pronociceptive role in the VLO in the rat formalin test due to its activation of AC - PKA pathway. Therefore, cerebral cortical 5-HT6 receptors could be a new target to develop analgesic drugs.
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