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, spinal GABAergic transmission via GABA_A 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 GABA_A-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.