Targeting glial activation to mitigate mirror‐image and extraterritorial neuropathic pain in a CCI model of neuropathic pain in male rats
Abstract Neuropathic pain (NP) arises from nerve damage or compression and often extends to the contralateral side of the body (mirror‐image pain, MP) and adjacent non‐injured areas (extraterritorial pain). This study investigates whether altered sensitivity in these contralateral and peripheral reg...
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Wiley
2025-04-01
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| Online Access: | https://doi.org/10.14814/phy2.70318 |
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| author | Mohammad‐Shafi Mojadadi Bahareh Amin Hossein Zeinali Samad Nazemi |
| author_facet | Mohammad‐Shafi Mojadadi Bahareh Amin Hossein Zeinali Samad Nazemi |
| author_sort | Mohammad‐Shafi Mojadadi |
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| description | Abstract Neuropathic pain (NP) arises from nerve damage or compression and often extends to the contralateral side of the body (mirror‐image pain, MP) and adjacent non‐injured areas (extraterritorial pain). This study investigates whether altered sensitivity in these contralateral and peripheral regions is mediated by glial cells, using the chronic constriction injury (CCI) model of NP. Thirty‐two male Wistar rats were randomly assigned into four groups (8/group): sham, CCI + vehicle, CCI + minocycline (MIN;10 mg/kg), and CCI + pentoxifylline (PTX;8 mg/kg). The CCI model was employed for NP induction. MIN and PTX were administered intraperitoneally from postoperative days (POD)4 to POD14, once daily. Pain responses were assessed on POD0, 2, 6, 10, and14 using Hargreaves, von Frey, and Tail‐flick tests. Western blot analysis was performed on POD14 to measure Iba1 and GFAP protein expression in the spinal cord hemispheres. Results revealed that post‐injury treatment with MIN and PTX significantly reduced contralateral thermal hyperalgesia, mechanical allodynia, and tail‐flick responses. Correspondingly, the contralateral spinal cord exhibited significantly decreased GFAP and Iba1 protein expression compared to the CCI + vehicle treated group. These findings suggest that post‐injury glial cell inhibition effectively mitigates neuropathic pain and prevents the development of MP and extraterritorial pain. This highlights the potential for clinical applications targeting glial cells to manage NP even after nerve injury. |
| format | Article |
| id | doaj-art-e1345873e07d482cad545e4ea817780c |
| institution | OA Journals |
| issn | 2051-817X |
| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-e1345873e07d482cad545e4ea817780c2025-08-20T02:28:50ZengWileyPhysiological Reports2051-817X2025-04-01138n/an/a10.14814/phy2.70318Targeting glial activation to mitigate mirror‐image and extraterritorial neuropathic pain in a CCI model of neuropathic pain in male ratsMohammad‐Shafi Mojadadi0Bahareh Amin1Hossein Zeinali2Samad Nazemi3Department of Immunology, School of Medicine Sabzevar University of Medical Sciences Sabzevar IranDepartment of Physiology and Pharmacology, School of Medicine Sabzevar University of Medical Sciences Sabzevar IranDepartment of Physiology and Pharmacology, School of Medicine Qom University of Medical Sciences Qom IranDepartment of Physiology and Pharmacology, Cellular and Molecular Research Center, School of Medicine Sabzevar University of Medical Sciences Sabzevar IranAbstract Neuropathic pain (NP) arises from nerve damage or compression and often extends to the contralateral side of the body (mirror‐image pain, MP) and adjacent non‐injured areas (extraterritorial pain). This study investigates whether altered sensitivity in these contralateral and peripheral regions is mediated by glial cells, using the chronic constriction injury (CCI) model of NP. Thirty‐two male Wistar rats were randomly assigned into four groups (8/group): sham, CCI + vehicle, CCI + minocycline (MIN;10 mg/kg), and CCI + pentoxifylline (PTX;8 mg/kg). The CCI model was employed for NP induction. MIN and PTX were administered intraperitoneally from postoperative days (POD)4 to POD14, once daily. Pain responses were assessed on POD0, 2, 6, 10, and14 using Hargreaves, von Frey, and Tail‐flick tests. Western blot analysis was performed on POD14 to measure Iba1 and GFAP protein expression in the spinal cord hemispheres. Results revealed that post‐injury treatment with MIN and PTX significantly reduced contralateral thermal hyperalgesia, mechanical allodynia, and tail‐flick responses. Correspondingly, the contralateral spinal cord exhibited significantly decreased GFAP and Iba1 protein expression compared to the CCI + vehicle treated group. These findings suggest that post‐injury glial cell inhibition effectively mitigates neuropathic pain and prevents the development of MP and extraterritorial pain. This highlights the potential for clinical applications targeting glial cells to manage NP even after nerve injury.https://doi.org/10.14814/phy2.70318CCI modelminocyclinemirror‐image painneuropathic painpentoxifylline |
| spellingShingle | Mohammad‐Shafi Mojadadi Bahareh Amin Hossein Zeinali Samad Nazemi Targeting glial activation to mitigate mirror‐image and extraterritorial neuropathic pain in a CCI model of neuropathic pain in male rats Physiological Reports CCI model minocycline mirror‐image pain neuropathic pain pentoxifylline |
| title | Targeting glial activation to mitigate mirror‐image and extraterritorial neuropathic pain in a CCI model of neuropathic pain in male rats |
| title_full | Targeting glial activation to mitigate mirror‐image and extraterritorial neuropathic pain in a CCI model of neuropathic pain in male rats |
| title_fullStr | Targeting glial activation to mitigate mirror‐image and extraterritorial neuropathic pain in a CCI model of neuropathic pain in male rats |
| title_full_unstemmed | Targeting glial activation to mitigate mirror‐image and extraterritorial neuropathic pain in a CCI model of neuropathic pain in male rats |
| title_short | Targeting glial activation to mitigate mirror‐image and extraterritorial neuropathic pain in a CCI model of neuropathic pain in male rats |
| title_sort | targeting glial activation to mitigate mirror image and extraterritorial neuropathic pain in a cci model of neuropathic pain in male rats |
| topic | CCI model minocycline mirror‐image pain neuropathic pain pentoxifylline |
| url | https://doi.org/10.14814/phy2.70318 |
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