Chronic pain affects 20% of the global population and current treatments fail to provide relief for most patients. To develop more effective therapies, we need a deeper understanding of the biological mechanisms that drive chronic pain. Our previous work has established a relationship between aging, telomere attrition, cellular senescence, and the intensity of chronic pain. The aim of this study was to further investigate the role of aging in chronic pain pathobiology, with a focus on the novel telomere-modulating gene, Zbtb48. Here we show a clear role for Zbtb48 in interplay between chronic pain and cellular ageing. Expression of Zbtb48 in the somatosensory system was quantified in healthy and neuropathic mice at 2 and 6months post nerve injury (SNI) or sham surgery using qPCR and immunohistochemistry. Our results show a significant and temporal upregulation of Zbtb48 in the DRGs and spinal cord of SNI-mice. In parallel, surgery in wild-type (WT) and Zbtb48 knockout mice (Zbtb48-/-) across two age groups (8-12weeks and 8-12months) revealed temporal changes in allodynia and hyperalgesia following von Frey, Hargreaves and pin prick assays. Mechanistically, SNI induced significant telomere length reductions in spinal glial cells and increased the expression of senescence-associated secretory factors, effects that were attenuated in Zbtb48-/-mice. Importantly, both Zbtb48-/- total body KO and sensory neuron-specific conditional KO Zbtb48 (cKO; Zbtb48fl x AdvCre) mice were protected from neuropathic pain. Lastly, potential Zbtb48 interaction partners were evaluated using proximity labelling mass spectrometry VIA a TurboID approach. Putative ZBTB48 interactors were identified, many of which are implicated in metabolism, cellular homeostasis and cell cycle dynamics. Collectively, these data establish a key role for ZBTB48 in driving cellular aging and promoting the development of long-term chronic pain. Theprotection provided by whole body and conditional knockout of Zbtb48 highlights its potential value as a new target for treating chronicpain.