PMID- 33730389 OWN - NLM STAT- MEDLINE DCOM- 20210826 LR - 20240226 IS - 1469-7580 (Electronic) IS - 0021-8782 (Print) IS - 0021-8782 (Linking) VI - 239 IP - 1 DP - 2021 Jul TI - The different mechanisms of peripheral and central TLR4 on chronic postsurgical pain in rats. PG - 111-124 LID - 10.1111/joa.13406 [doi] AB - Chronic postsurgical pain (CPSP) is a common complication after surgery; however, the underlying mechanisms of CPSP are poorly understood. As one of the most important inflammatory pathways, the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-kappaB) signaling pathway plays an important role in chronic pain. However, the precise role of the TLR4/NF-kappaB signaling pathway in CPSP remains unclear. In the present study, we established a rat model of CPSP induced by skin/muscle incision and retraction (SMIR) and verified the effects and mechanisms of central and peripheral TLR4 and NF-kappaB on hyperalgesia in SMIR rats. The results showed that TLR4 expression was increased in both the spinal dorsal horn and dorsal root ganglia (DRGs) of SMIR rats. However, the TLR4 expression pattern in the spinal cord was different from that in DRGs. In the spinal cord, TLR4 was expressed in both neurons and microglia, whereas it was expressed in neurons but not in satellite glial cells in DRGs. Further results demonstrate that the central and peripheral TLR4/NF-kappaB signaling pathway is involved in the SMIR-induced CPSP by different mechanisms. In the peripheral nervous system, we revealed that the TLR4/NF-kappaB signaling pathway induced upregulation of voltage-gated sodium channel 1.7 (Nav1.7) in DRGs, triggering peripheral hyperalgesia in SMIR-induced CPSP. In the central nervous system, the TLR4/NF-kappaB signaling pathway participated in SMIR-induced CPSP by activating microglia in the spinal cord. Ultimately, our findings demonstrated that activation of the peripheral and central TLR4/NF-kappaB signaling pathway involved in the development of SMIR-induced CPSP. CI - (c) 2021 Anatomical Society. FAU - Han, Xuemin AU - Han X AD - The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China. AD - The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. AD - Children's Hospital of Soochow University, Soochow, China. FAU - Shao, Jinping AU - Shao J AD - Department of Human Anatomy, School of Basic Medicine, Zhengzhou University, Zhengzhou, China. AD - Institute of Neuroscience, Zhengzhou University, Zhengzhou, China. FAU - Ren, Xiuhua AU - Ren X AD - Department of Human Anatomy, School of Basic Medicine, Zhengzhou University, Zhengzhou, China. AD - Institute of Neuroscience, Zhengzhou University, Zhengzhou, China. FAU - Li, Yaru AU - Li Y AD - The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China. AD - The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Yu, Wenli AU - Yu W AD - Department of Human Anatomy, School of Basic Medicine, Zhengzhou University, Zhengzhou, China. AD - Institute of Neuroscience, Zhengzhou University, Zhengzhou, China. FAU - Lin, Caihong AU - Lin C AD - Department of Human Anatomy, School of Basic Medicine, Zhengzhou University, Zhengzhou, China. AD - Institute of Neuroscience, Zhengzhou University, Zhengzhou, China. FAU - Li, Lei AU - Li L AD - Department of Human Anatomy, School of Basic Medicine, Zhengzhou University, Zhengzhou, China. AD - Institute of Neuroscience, Zhengzhou University, Zhengzhou, China. FAU - Sun, Yanyan AU - Sun Y AD - Department of Human Anatomy, School of Basic Medicine, Zhengzhou University, Zhengzhou, China. AD - Institute of Neuroscience, Zhengzhou University, Zhengzhou, China. FAU - Xu, Bo AU - Xu B AD - Department of Anesthesiology, General Hospital of Southern Theatre Command of PLA, Guangzhou, China. FAU - Luo, Huan AU - Luo H AD - Klinik fur Augenheilkunde, Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health, Germany. FAU - Zhu, Changlian AU - Zhu C AD - Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Gothenburg University, Gothenburg, Sweden. FAU - Cao, Jing AU - Cao J AUID- ORCID: 0000-0003-3124-4780 AD - Department of Human Anatomy, School of Basic Medicine, Zhengzhou University, Zhengzhou, China. AD - Institute of Neuroscience, Zhengzhou University, Zhengzhou, China. FAU - Li, Zhisong AU - Li Z AD - The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China. AD - The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210317 PL - England TA - J Anat JT - Journal of anatomy JID - 0137162 RN - 0 (CD11b Antigen) RN - 0 (NAV1.7 Voltage-Gated Sodium Channel) RN - 0 (NF-kappa B) RN - 0 (Scn9a protein, rat) RN - 0 (Tlr4 protein, rat) RN - 0 (Toll-Like Receptor 4) SB - IM MH - Animals MH - CD11b Antigen/metabolism MH - Chronic Pain/*metabolism MH - Ganglia, Spinal/metabolism MH - Hyperalgesia/metabolism MH - Male MH - Microglia/*metabolism MH - NAV1.7 Voltage-Gated Sodium Channel/metabolism MH - NF-kappa B/metabolism MH - Pain, Postoperative/*metabolism MH - Rats, Sprague-Dawley MH - Spinal Cord/*metabolism MH - Toll-Like Receptor 4/*metabolism MH - Up-Regulation MH - Rats PMC - PMC8197940 OTO - NOTNLM OT - NF-kappaB OT - Nav1.7 OT - TLR4 OT - chronic postoperative pain OT - microglia OT - skin/muscle incision and retraction COIS- The authors declare no conflict of interest. EDAT- 2021/03/18 06:00 MHDA- 2021/08/27 06:00 PMCR- 2023/07/01 CRDT- 2021/03/17 17:52 PHST- 2021/01/21 00:00 [revised] PHST- 2020/09/17 00:00 [received] PHST- 2021/01/22 00:00 [accepted] PHST- 2021/03/18 06:00 [pubmed] PHST- 2021/08/27 06:00 [medline] PHST- 2021/03/17 17:52 [entrez] PHST- 2023/07/01 00:00 [pmc-release] AID - JOA13406 [pii] AID - 10.1111/joa.13406 [doi] PST - ppublish SO - J Anat. 2021 Jul;239(1):111-124. doi: 10.1111/joa.13406. Epub 2021 Mar 17.