Experimental Validation and Multimodal Spectroscopic Profiling of the Neuroprotective Potential of Costunolide in Chemotherapy‐Induced Neuropathic Pain

Neuropathic pain is a complex chronic condition resulting from injury to the nerve. Paclitaxel (PTX) is a commonly used chemotherapeutic drug, but it is usually associated with peripheral neuropathy. Costunolide (COS), a bioactive sesquiterpene lactone, exhibits potent neuroprotective, anti-inflammatory, antioxidant, and anti-apoptotic properties. The current study aimed to investigate the efficacy of COS in attenuating PTX-induced neuropathic pain using advanced spectroscopic, histological and biochemical analyses. Findings from the study revealed that administration with COS significantly improved the pain parameters, including mechanical allodynia, thermal hyperalgesia, and cold allodynia by increasing the pain thresholds. Muscle strength and motor coordination also improved significantly following administration of COS. Results from the Raman spectral analysis revealed distinct PTX-induced biochemical disruptions, especially in the lipids and proteins, which were subsequently normalized by COS. FTIR spectra demonstrated that COS mitigated PTX-induced damage to the myelin sheath, hence preserving the biochemical integrity. The tissue oxygenation (StO₂) profile was also improved. COS preserved neuronal architecture, reduced PTX-induced apoptosis, and maintained spinal cord and sciatic nerve structure. It also increased the level of antioxidants, that is, GSH, GST, and catalase, while reducing the level of oxidative stress markers (MPO, EPO, LPO, NO). Together, these findings establish COS as a promising candidate for the treatment of peripheral neuropathy. Its multimodal protective mechanisms-captured at both molecular and cellular levels- highlight its potential to counteract PTX-induced neurotoxicity.