Diet-induced obesity exacerbates and prolongs postoperative pain via peripheral DRG transcriptional changes in rats.

Background: Obesity is a known risk factor for the increased severity and persistence of postoperative pain; however, the underlying mechanisms remain incompletely understood. The primary objective of this study was to elucidate the peripheral mechanisms underlying obesity-related exacerbation and prolongation of postoperative pain. A comparative transcriptomic analysis of the spinal cord was performed as a secondary exploratory assessment. Methods: Male Wistar rats were fed a high-fat diet (HFD) or standard diet (SD) to induce obesity. Postoperative pain was modeled using the plantar incision (Brennan) model. Pain-related behaviors including spontaneous pain, mechanical withdrawal thresholds, and thermal withdrawal latencies were evaluated longitudinally. Electrophysiological recordings were performed to assess the mechanical sensitivity of primary afferent fibers in the tibial nerve-plantar skin preparation. Transcriptome analyses were conducted on the dorsal root ganglia (DRG) and spinal cord on postoperative day 4 to identify the differentially expressed genes (DEGs) associated with obesity-related pain modulation. Results: Rats fed an HFD exhibited increased body weight and body fat percentage compared with SD-fed rats. Following surgery, the HFD-fed rats showed significantly higher spontaneous pain scores and prolonged mechanical hypersensitivity than the SD-fed rats, whereas preoperative pain sensitivity did not differ between the groups. Electrophysiological analysis revealed no significant differences in the mechanical thresholds or stimulus-response relationship of mechanosensitive C-fibers between the groups. Transcriptome analysis identified 19 DEGs in the DRG of HFD-fed rats; however, no genes in the spinal cord dorsal horn met the statistical threshold for differential expression under the present analytical conditions. Pathway analysis indicated that the DRG DEGs were primarily associated with endocrine disorders and lipid metabolism. Conclusion: Diet-induced obesity exacerbated and prolonged postoperative pain in rats. This effect may be associated with peripheral molecular adaptations in primary sensory neurons, including changes in DRG gene expression related to metabolic and endocrine pathways. In contrast, no genes met the statistical threshold for differential expression in the spinal cord dorsal horn on postoperative day 4 under the present analytical conditions.