Lin28b In Trigeminal Nerve Injury-Induced Orofacial Hyperalgesia

This study investigates the mechanism of Lin28b in trigeminal nerve injury-induced orofacial pain and associated anxiety-depression behaviors, addressing the lack of research on neural regeneration and pain-related emotional disorders. Male C57 mice were subjected to infraorbital nerve crush injury to evaluate orofacial hyperalgesia using the mechanical head withdrawal threshold (mHWT) and to assess anxiety- and depression-like behaviors through the elevated plus-maze (EPM), open field (OFT), and forced swim tests (FST). The expression levels of Lin28b in the trigeminal ganglia (TG) and spinal trigeminal nucleus (Sp5) were quantified using RT-PCR and Western blot analysis. To further investigate the functional role of Lin28b, systemic overexpression was induced in M2rtTAtg/+; hLin28btg/+ mice, and its effects on pain sensitivity and behavioral outcomes were examined. All experimental procedures were conducted in compliance with ethical standards and approved by the Institutional Ethics Committee. Trigeminal nerve injury induced orofacial hyperalgesia and anxiety- and depression-like behaviors in mice, accompanied by upregulated expression of Lin28b and Gpr158 in the TG and Sp5. Systemic overexpression of Lin28b significantly alleviated orofacial hyperalgesia and anxiety and depression, correlating with further elevated Lin28b levels in the TG and Sp5. Lin28b overexpression mitigates trigeminal nerve injury-induced orofacial hyperalgesia and anxiety-depression, highlighting its potential as a therapeutic target for neuropathic pain and associated emotional disorders.