Development and validation of clinically Mimicable model of frostbite injury-induced chronic pain

In this study, we employed deep-frozen magnets to induce frostbite injury and conducted validation for chronic pain through assessments of face, predictive, and mechanistic validity. Behavioral assays demonstrated that animals with frostbite injury exhibited significant mechanical, thermal & cold hypersensitivity in injured rats. Further, molecular analysis indicated that frostbite injury triggered the activation of TRP channels (TRPA1 and TRPM8), microgliosis, and increased neuroinflammation in the dorsal root ganglion (DRG) and spinal cord of rats. Notably, NR2B protein expressions were significantly upregulated in the DRG of injured rats, while no changes were observed in spinal NR2B expressions. Furthermore, the administration of ibuprofen (25, 50, and 100 mg/kg, i.p.) resulted in a significant improvement in behavioral, biochemical, and molecular alterations in frostbite-injured rats. Overall, results suggested that established frostbite model effectively recapitulates face, pharmacological, and mechanistic validity, highlighting its potential for screening future treatment modalities and exploring the intricate mechanisms associated with frostbite-induced chronic pain.PMID:38176530 | DOI:10.1016/j.cellsig.2023.111028
Source: Cellular Signalling - Category: Cytology Authors: Source Type: research