INTRODUCTION: Neuropathic pain remains a significant therapeutic challenge, affecting about 7-10% of the global population, with rising rates in cancer and diabetes. Chemotherapy-induced peripheral neuropathy (CIPN), especially from oxaliplatin, is hard to treat because current medications rarely fully relieve pain and often cause side effects.

AIM(S): HBK-15, a multimodal compound, has previously demonstrated antinociceptive effects in the formalin test and reduced allodynia in diabetic neuropathy; however, its effects in CIPN have not been investigated.

METHOD(S): Therefore, we aimed to evaluate the activity of HBK-15 in preventing the development of pain sensitization (mechanical allodynia and thermal hyperalgesia) in an oxaliplatin-induced neuropathic pain model. Additionally, we examined potential mechanisms by assessing inflammatory and antioxidant-related markers in the spinal cord using qPCR for Nrf2 mRNA expression and Western blotting for IL-1β, TNF-α, Nrf2, and phosphorylated Nrf2 (pNrf2).

RESULTS: HBK-15 significantly reduced mechanical allodynia in the von Frey test after 7 days of treatment but had no effect during the acute phase of neuropathy. In contrast, the reduction of cold-induced thermal hyperalgesia was observed only in the early stage of symptom development at a dose of 5 mg/kg, with no effectiveness at later time points. Molecular analyses showed no significant changes in Nrf2 mRNA expression or in the protein levels of IL-1β, TNF-α, Nrf2, or pNrf2 following HBK-15 treatment.

CONCLUSIONS: These findings indicate that the analgesic effects of HBK-15 are likely not primarily mediated by inflammatory or Nrf2-related antioxidant pathways and may involve alternative mechanisms, possibly related to ion channel activity.

FINANCIAL SUPPORT: The study was financed by the Students’ Scientific Society of JU MC within the Students’ Grant Competition (2024/2025)