The role and mechanism of fatty acid-binding protein 7 in spinal reactive astrocytes in prolonged postoperative pain induced by high-fat diet.

Obesity markedly exacerbates nociceptive sensitivity and substantially compromises the quality of life of affected people. Astrocytes orchestrate metabolic regulation and homeostatic maintenance in the central nervous system. Notably, fatty acid binding protein 7 (FABP7) is highly expressed in astrocytes that governs intracellular fatty acid uptake and transport. While systemic hyperlipidemia is pathognomonic of obesity, the mechanistic contribution of FABP7 in astrocytes to obesity-associated pain pathophysiology remains poorly characterized. The present study established a model of high-fat diet (HFD)-induced obesity combined with a standardized hind paw surgical incision paradigm, aiming to unveil the role of astrocytic FABP7 in HFD-induced chronic pain. Furthermore, an in vitro high-fat environment was induced by palmitic acid (PA),aiming to investigate the molecular mechanisms by which primary astrocytes were activated into the A1 phenotype to mediate neuroinflammation. FABP7 was overexpressed in the spinal dorsal of HFD mice. The activation of A1-type astrocytes and neuroinflammation cascades involving elevated iNOS eventually resulted in mechanical allodynia in HFD mice. Pharmacological inhibition of FABP7 via an intraperitoneal administration of SBFI-26 (20 mg/kg) significantly attenuated the paw withdrawal mechanical threshold and inhibited the A1-type astrocytes activation. PA-induced high-fat conditions promoted lipid droplet accumulation and upregulated FABP7 in astrocytes. Pharmacological inhibition of FABP7 using SBFI-26 (100 μmol/L) significantly suppressed the neurotoxic C3-positive A1 astrocyte phenotype, reduced intracellular lipid droplet accumulation, thereby inhibiting the activation of A1-type astrocytes and alleviating neuroinflammation. Overall, FABP7-mediated astrocytic reprogramming was a critical nexus bridging obesity with chronic pain. A1-astrocyte polarization initiated neuroinflammatory amplification, forming a feedforward loop perpetuating central sensitization. Our findings are expected to offer a viable target for metabolic pain management.