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In neuropathic pain states, nociceptive stimuli activate LC. This study examined the expression and localization of BDNF and NE neuron-specific proteins in the LC of mice with cancer-induced bone pain (CIBP). Behavioral experiments demonstrated that CIBP mice exhibited persistent spontaneous pain, mechanical and thermal hyperalgesia, and deficits in locomotor activity and motor coordination. H&amp;E and TRAP staining revealed trabecular bone destruction and increased in osteoclast activity. Immunostaining showed elevated expression of neuronal activity marker c-Fos in the LC. Additionally, upregulation of noradrenergic markers - tyrosine hydroxylase (TH) and dopamine \u03b2-hydroxylase (DBH) \u2013 as well as brain-derived neurotrophic factor (BDNF), was observed in the LC. In vitro studies indicated that inhibition of the BDNF\/TrkB signalling pathway reduced the expression of noradrenergic markers. Anterograde tracing, achieved by Fluoro-ruby injection into the LC and subsequent detection of Fluoro-ruby colocalised with TH and DBH in spinal cord, confirmed LC-spinal cord projections. Immunofluorescence analysis demonstrated increased fluorescence intensities of TH, DBH, c-Fos, phosphorylated cAMP-response element- binding protein (pCREB), and \u03b1<jats:sub>2A<\/jats:sub> receptor in the spinal cord, alongside reduced intensities of enkephalin (ENK) and GABA A Receptor \u03b22 (GABRB2). Western blotting further corroborated elevated expression levels of TH and c-Fos in spinal cord tissue. In summary, CIBP mice exhibited enhanced neuronal activity in the LC, upregulation of noradrenergic markers, and BDNF\/TrkB-mediated modulation of noradrenergic neurons. Concurrently, inhibitory signalling was attenuated in the SDH.<\/jats:p>","DOI":"10.1371\/journal.pone.0330207","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T18:05:42Z","timestamp":1755194742000},"page":"e0330207","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alteration of BDNF and noradrenergic markers in locus coeruleus in a mouse model of cancer-induced bone 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