CAV-1 Overexpression Exacerbates the Manifestation in EPAC-1-Induced Chronic Postsurgical Pain in Rats
Purpose. Caveolae (CAV) are an invaginated microcapsule with the shape of Ω 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 p...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2022-01-01
|
| Series: | Pain Research and Management |
| Online Access: | http://dx.doi.org/10.1155/2022/8566840 |
| _version_ | 1798040857498091520 |
|---|---|
| author | Qian Hua Shiren Shen Yibin Qin Su Cao |
| author_facet | Qian Hua Shiren Shen Yibin Qin Su Cao |
| author_sort | Qian Hua |
| collection | DOAJ |
| description | Purpose. Caveolae (CAV) are an invaginated microcapsule with the shape of Ω 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. |
| first_indexed | 2024-04-11T22:13:28Z |
| format | Article |
| id | doaj.art-36d77a3fcc3b4e1fbf7f8d22fd893dcf |
| institution | Directory Open Access Journal |
| issn | 1918-1523 |
| language | English |
| last_indexed | 2024-04-11T22:13:28Z |
| publishDate | 2022-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Pain Research and Management |
| spelling | doaj.art-36d77a3fcc3b4e1fbf7f8d22fd893dcf2022-12-22T04:00:29ZengHindawi LimitedPain Research and Management1918-15232022-01-01202210.1155/2022/8566840CAV-1 Overexpression Exacerbates the Manifestation in EPAC-1-Induced Chronic Postsurgical Pain in RatsQian Hua0Shiren Shen1Yibin Qin2Su Cao3Medical CollegeDepartment of AnesthesiologyDepartment of AnesthesiologyDepartment of AnesthesiologyPurpose. Caveolae (CAV) are an invaginated microcapsule with the shape of Ω 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.http://dx.doi.org/10.1155/2022/8566840 |
| spellingShingle | Qian Hua Shiren Shen Yibin Qin Su Cao CAV-1 Overexpression Exacerbates the Manifestation in EPAC-1-Induced Chronic Postsurgical Pain in Rats Pain Research and Management |
| title | CAV-1 Overexpression Exacerbates the Manifestation in EPAC-1-Induced Chronic Postsurgical Pain in Rats |
| title_full | CAV-1 Overexpression Exacerbates the Manifestation in EPAC-1-Induced Chronic Postsurgical Pain in Rats |
| title_fullStr | CAV-1 Overexpression Exacerbates the Manifestation in EPAC-1-Induced Chronic Postsurgical Pain in Rats |
| title_full_unstemmed | CAV-1 Overexpression Exacerbates the Manifestation in EPAC-1-Induced Chronic Postsurgical Pain in Rats |
| title_short | CAV-1 Overexpression Exacerbates the Manifestation in EPAC-1-Induced Chronic Postsurgical Pain in Rats |
| title_sort | cav 1 overexpression exacerbates the manifestation in epac 1 induced chronic postsurgical pain in rats |
| url | http://dx.doi.org/10.1155/2022/8566840 |
| work_keys_str_mv | AT qianhua cav1overexpressionexacerbatesthemanifestationinepac1inducedchronicpostsurgicalpaininrats AT shirenshen cav1overexpressionexacerbatesthemanifestationinepac1inducedchronicpostsurgicalpaininrats AT yibinqin cav1overexpressionexacerbatesthemanifestationinepac1inducedchronicpostsurgicalpaininrats AT sucao cav1overexpressionexacerbatesthemanifestationinepac1inducedchronicpostsurgicalpaininrats |