INVESTIGATING HOW AN IMMUNE CHALLENGE IMPACTS THE TRAJECTORY OF CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY

Chemotherapy-induced peripheral neuropathy (CIPN) is an unfortunate side effect of chemotherapy treatment that causes neuropathic pain. Pain resulting from CIPN can lead patients to end their treatment course early, emphasizing the need to prevent or resolve CIPN. A medication that causes CIPN is Paclitaxel (PTX), which induces immunological and neuronal changes and activates interferon (IFN) signaling. While IFNs have been shown to modulate pain, their role in promoting resolution of CIPN has yet to be elucidated. We hypothesize that interfering with type I IFN signaling will alter the natural resolution of CIPN. Male and female mice received a cumulative dose of 16mg/kg of PTX (intraperitoneally) to induce pain. Tactile stimulation of the hind paw was performed over a 6-8-week period to assess changes in hypersensitivity. Poly(I:C), a synthetic double-stranded RNA molecule that induces a type I IFN response, was injected during peak pain to determine if a secondary stimulus could alter the trajectory of CIPN. To better understand the role of IFN signaling, similar experiments were conducted in IFN-receptor knock-out mice and wild-type mice that received IFN-beta. We found that PTX treatment causes hyperalgesia, which resolves in both sexes. Poly(I:C) accelerated recovery from CIPN, while mice lacking the IFN-receptor did not recover. Mice that received IFN-beta had faster recovery from hypersensitivity. These results suggest that IFNs play an important role in CIPN recovery, highlighting their potential as a future therapeutic.