How spinal GABAergic circuits modulate cerebral processing of postsurgical pain
Post-surgical pain affects millions each year, hindering recovery and quality of life. Surgical procedures cause tissue damage and inflammation, leading to peripheral and central sensitization, resulting in pain at rest or mechanical and heat hyperalgesia. In a rat model for post-surgical pain, spin...
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Elsevier
2025-02-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825000349 |
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| author | Bruno Pradier Daniel Segelcke Nathalie Just Mirjam Augustin Nina Nagelmann Cornelius Faber Esther Pogatzki-Zahn |
| author_facet | Bruno Pradier Daniel Segelcke Nathalie Just Mirjam Augustin Nina Nagelmann Cornelius Faber Esther Pogatzki-Zahn |
| author_sort | Bruno Pradier |
| collection | DOAJ |
| description | Post-surgical pain affects millions each year, hindering recovery and quality of life. Surgical procedures cause tissue damage and inflammation, leading to peripheral and central sensitization, resulting in pain at rest or mechanical and heat hyperalgesia. In a rat model for post-surgical pain, spinal GABAergic transmission via GABAA receptors reduces mechanical hypersensitivity but has no effect on pain at rest. While fMRI studies show consistent brain activity changes during mechanical stimulation in post-surgical pain, central processing of pain at rest and the role of spinal GABAergic circuits on surgical pain processing is currently unclear. The aim of this study was to evaluate the influence of an acute surgical incision injury, a proxy for post-surgical pain, on the cerebral processing of pain at rest and mechanical hypersensitivity, and to assess the influence of spinal GABAA-circuits on this processing. In rats, a unilateral incision affected sensorimotor and thalamo-limbic subnetworks at rest and following mechanical stimulation, indicating changes in neural processing relevant to pain at rest and mechanical hypersensitivity in post-surgical pain. Enhancing spinal GABAergic tone increased functional connectivity (FC) in parts of these subnetworks during mechanical stimulation, but not at rest, highlighting spino-cerebral interactions in pain regulation relevant for mechanical hypersensitivity and potentially the transisition to chronic pain after surgery but likely not for pain at rest. These findings underscore the complex and interconnected nature of brain networks in post-surgical pain processing, and provide insights into potential spinal targets for pharmacological intervention to alleviate post-surgical pain and prevent it's chronification. |
| format | Article |
| id | doaj-art-a92927ec72c3449f917a0914691e5e3e |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | Pharmacological Research |
| spelling | doaj-art-a92927ec72c3449f917a0914691e5e3e2025-02-08T04:59:51ZengElsevierPharmacological Research1096-11862025-02-01212107609How spinal GABAergic circuits modulate cerebral processing of postsurgical painBruno Pradier0Daniel Segelcke1Nathalie Just2Mirjam Augustin3Nina Nagelmann4Cornelius Faber5Esther Pogatzki-Zahn6Department of Anesthesiology Intensive Care and Pain Medicine of the University Hospital Münster, Germany; Clinic of Radiology, Translational Research Imaging Center, GermanyDepartment of Anesthesiology Intensive Care and Pain Medicine of the University Hospital Münster, GermanyClinic of Radiology, Translational Research Imaging Center, Germany; present address: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, DenmarkDepartment of Anesthesiology Intensive Care and Pain Medicine of the University Hospital Münster, GermanyClinic of Radiology, Translational Research Imaging Center, GermanyClinic of Radiology, Translational Research Imaging Center, GermanyDepartment of Anesthesiology Intensive Care and Pain Medicine of the University Hospital Münster, Germany; Correspondence to: Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Albert-Schweitzer-Campus 1, A1, Muenster 48149, GermanyPost-surgical pain affects millions each year, hindering recovery and quality of life. Surgical procedures cause tissue damage and inflammation, leading to peripheral and central sensitization, resulting in pain at rest or mechanical and heat hyperalgesia. In a rat model for post-surgical pain, spinal GABAergic transmission via GABAA receptors reduces mechanical hypersensitivity but has no effect on pain at rest. While fMRI studies show consistent brain activity changes during mechanical stimulation in post-surgical pain, central processing of pain at rest and the role of spinal GABAergic circuits on surgical pain processing is currently unclear. The aim of this study was to evaluate the influence of an acute surgical incision injury, a proxy for post-surgical pain, on the cerebral processing of pain at rest and mechanical hypersensitivity, and to assess the influence of spinal GABAA-circuits on this processing. In rats, a unilateral incision affected sensorimotor and thalamo-limbic subnetworks at rest and following mechanical stimulation, indicating changes in neural processing relevant to pain at rest and mechanical hypersensitivity in post-surgical pain. Enhancing spinal GABAergic tone increased functional connectivity (FC) in parts of these subnetworks during mechanical stimulation, but not at rest, highlighting spino-cerebral interactions in pain regulation relevant for mechanical hypersensitivity and potentially the transisition to chronic pain after surgery but likely not for pain at rest. These findings underscore the complex and interconnected nature of brain networks in post-surgical pain processing, and provide insights into potential spinal targets for pharmacological intervention to alleviate post-surgical pain and prevent it's chronification.http://www.sciencedirect.com/science/article/pii/S1043661825000349BOLD fMRI and resting-state and mechanical stimulationBrain network and graph theoryIncision model and post-operative painNon-evoked pain and evoked painIntrathecal and muscimol and bicuculline |
| spellingShingle | Bruno Pradier Daniel Segelcke Nathalie Just Mirjam Augustin Nina Nagelmann Cornelius Faber Esther Pogatzki-Zahn How spinal GABAergic circuits modulate cerebral processing of postsurgical pain Pharmacological Research BOLD fMRI and resting-state and mechanical stimulation Brain network and graph theory Incision model and post-operative pain Non-evoked pain and evoked pain Intrathecal and muscimol and bicuculline |
| title | How spinal GABAergic circuits modulate cerebral processing of postsurgical pain |
| title_full | How spinal GABAergic circuits modulate cerebral processing of postsurgical pain |
| title_fullStr | How spinal GABAergic circuits modulate cerebral processing of postsurgical pain |
| title_full_unstemmed | How spinal GABAergic circuits modulate cerebral processing of postsurgical pain |
| title_short | How spinal GABAergic circuits modulate cerebral processing of postsurgical pain |
| title_sort | how spinal gabaergic circuits modulate cerebral processing of postsurgical pain |
| topic | BOLD fMRI and resting-state and mechanical stimulation Brain network and graph theory Incision model and post-operative pain Non-evoked pain and evoked pain Intrathecal and muscimol and bicuculline |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825000349 |
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