Abstract
Clinical studies have established that repeated blast traumatic brain injury (rbTBI) can result in chronic pain conditions, with outcomes exhibiting notable sex-dependent differences. However, limited preclinical rbTBI models have systematically investigated the behavioral and neuropathological outcomes of female subjects. In the present study, adult female rats were subjected to repeated blast exposures, and the subsequent development of chronic pain-related behaviors and neuropathological changes was assessed. Repeated blast events induced robust mechanical and thermal hypersensitivity beginning 48 h post-injury and persisted through 12 weeks, accompanied by anxiety and depressive-like behaviors at the chronic time point. These behavioral alterations were associated with increased glial activity, as evidenced by Glial Fibrillary Acidic Protein (GFAP) and Ionized Calcium-Binding Adaptor Molecule 1 (IBA-1) in the frontal cortex and posterior nucleus regions at 12 weeks following injury. Notably, expression levels of neuropeptide markers, Calcitonin Gene-Related Peptide (CGRP) and Substance P (SP), remained unchanged. Collectively, these findings suggest that chronic pain behaviors following rbTBI in females are mediated primarily by sustained glial activation rather than neuropeptide dysregulation.