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Resolvin alleviates mechanical and heat, tumor-induced, hyperalgesia by inhibition of HIF-1 Alpha

Poster Session F - Tuesday, April 1, 2025, 8:00 – 10:00 am EDT, Back Bay Ballroom/Republic Ballroom

Laura Neal¹, Kira Braun², Iryna Khasabov³, Donald Simone³; ¹Macalester College, ²Amherst College, ³University of Minnesota

More than 60% of patients with primary or metastatic osteosarcoma experience severe chronic pain. This pain is exacerbated by cancer treatments such as chemotherapy. Cancer-related pain is hard to treat as it is inflammatory, tumorigenic, and neuropathic. Cancer patients currently lack sufficient non-opioid pain treatment. Resolvin (RvD1), a pro-resolving antinociceptive product of ω−3 polyunsaturated fatty acids, may alleviate tumor-induced hyperalgesia by resolving inflammation. We have previously shown the antinociceptive properties of Resolvin in tumor-bearing mice, but the exact mechanism through which Resolvin alleviates pain is not yet understood. We hypothesized that Resolvin decreases levels of Hypoxia Inducible Factor 1-Alpha in the central nervous system. Our data from qPCR of the lumbar spinal cord shows that tumor-bearing mice treated with Resolvin have lower levels of HIF-1a in the CNS than untreated tumor-bearing mice. Tumor-bearing mice also have higher levels of HIF-1a than naive mice, as HIF-1a is associated with tumor survival. To explore this possible mechanism of Resolvin, we injected tumor-bearing mice with si-RNA to block HIF-1a. Through Von Frey and the Hargreaves test we show that this treatment significantly attenuates heat and mechanical hyperalgesia. This shows that HIF-1a is directly involved in the central pain pathways of tumor-related mechanical and heat hyperalgesia and that this pathway can be intercepted through treatment with Resolvin. These findings support Resolvin being a viable treatment option to attenuate osteosarcoma induced chronic pain.

Topic Area: PERCEPTION & ACTION: Other