PMID- 35958678 OWN - NLM STAT- MEDLINE DCOM- 20220815 LR - 20220817 IS - 1918-1523 (Electronic) IS - 1203-6765 (Print) IS - 1203-6765 (Linking) VI - 2022 DP - 2022 TI - CAV-1 Overexpression Exacerbates the Manifestation in EPAC-1-Induced Chronic Postsurgical Pain in Rats. PG - 8566840 LID - 10.1155/2022/8566840 [doi] LID - 8566840 AB - PURPOSE: Caveolae (CAV) are an invaginated microcapsule with the shape of Omega on the surface of the cell membrane. Caveolin-1 (CAV-1) is involved in neuropathic pain, and adenosine monophosphate (AMP)-exchange protein directly activated by cAMP1 (EPAC-1) is a potential therapeutic target for chronic pain. However, whether EPAC-1 promotes chronic postsurgical pain (CPSP) through CAV-1 has not been reported. Here, we aim to investigate the underlying mechanism of CAV in CPSP. METHODS: All the rats were divided into 9 groups, including the Naive group, Sham group, skin/muscle incision and retraction (SMIR) group, SMIR + CAV-1 siRNA group, SMIR + control siRNA group, SMIR (7 days)+Saline group, SMIR (7 days)+CE3F4 group, 8-PCPT group, and Saline group. The CPSP rat model was established after SMIR. A mechanical withdrawal threshold (MWT) was recorded to evaluate the animal's behavior. Western blotting and immunofluorescent were performed to detect the protein expression levels of EPAC-1 and P-CAV-1. RESULTS: EPAC-1 and CAV-1 were both overexpressed after operation, particularly in astrocytes, microglia, and neurons of spinal marrow (all P < 0.05). Interestingly, CAV-1 siRNA can partly reverse the SMIR-induced hypersensitivity, but there was no effect on EPAC-1. Besides, EPAC-1 blockage partly reversed the SMIR-induced hypersensitivity and CAV-1 overexpression, and EPAC-1 activation promoted CAV-1 overexpression and hypersensitivity in normal rats (all P < 0.05). CONCLUSION: CAV-1 mediates the functional coupling of microglia, astrocytes, and neurons, and thus EPAC-1/CAV-1 plays an important role in CPSP exacerbation. CI - Copyright (c) 2022 Qian Hua et al. FAU - Hua, Qian AU - Hua Q AUID- ORCID: 0000-0002-3474-1777 AD - Medical College, Nantong University, Nantong, Jiangsu 226001, China. FAU - Shen, Shiren AU - Shen S AUID- ORCID: 0000-0003-3547-5375 AD - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu 226001, China. FAU - Qin, Yibin AU - Qin Y AUID- ORCID: 0000-0002-8484-0968 AD - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu 226001, China. FAU - Cao, Su AU - Cao S AUID- ORCID: 0000-0003-0754-7087 AD - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu 226001, China. LA - eng PT - Journal Article DEP - 20220731 PL - United States TA - Pain Res Manag JT - Pain research & management JID - 9612504 RN - 0 (Guanine Nucleotide Exchange Factors) RN - 0 (RNA, Small Interfering) SB - IM MH - Animals MH - *Caveolae/metabolism MH - *Chronic Pain/etiology/metabolism MH - Guanine Nucleotide Exchange Factors/genetics MH - Pain, Postoperative/metabolism MH - RNA, Small Interfering MH - Rats MH - Rats, Sprague-Dawley PMC - PMC9357801 COIS- The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2022/08/13 06:00 MHDA- 2022/08/16 06:00 PMCR- 2022/07/31 CRDT- 2022/08/12 03:01 PHST- 2021/07/28 00:00 [received] PHST- 2022/01/06 00:00 [revised] PHST- 2022/06/27 00:00 [accepted] PHST- 2022/08/12 03:01 [entrez] PHST- 2022/08/13 06:00 [pubmed] PHST- 2022/08/16 06:00 [medline] PHST- 2022/07/31 00:00 [pmc-release] AID - 10.1155/2022/8566840 [doi] PST - epublish SO - Pain Res Manag. 2022 Jul 31;2022:8566840. doi: 10.1155/2022/8566840. eCollection 2022.