Simultaneous hyperbaric oxygen therapy during systemic chemotherapy reverses chemotherapy-induced peripheral neuropathy by inhibiting TLR4 and TRPV1 activation in the central and peripheral nervous system

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is considered one of the most common sequelae in patients with cancer who experience consistent abnormal sensations or pain symptoms during or after paclitaxel (PAC) chemotherapy. Transient receptor potential vanilloid 1 (TRPV1) and toll-like receptor 4 (TLR4) have been reported to interact in the nervous system in patients with CIPN. The antinociceptive effects of hyperbaric oxygen therapy (HBOT) on CIPN was demonstrated in this study through behavior tests. Using a CIPN rat model, we examined the effects of simultaneous HBOT (SHBOT) administration during chemotherapy and discovered that SHBOT achieved better reversal effects than chemotherapy alone. Twenty-four rats were randomly allocated to four groups: control, PAC, SHBOT, and HBOT after PAC groups. Behavior tests were performed to evaluate mechanical allodynia and thermal hyperalgesia status. Tissues from the spinal cord and dorsal root ganglions were collected, and TLR4 and TRPV1 expression and microglial activation were investigated through immunofluorescence (IF) staining. The mechanical and thermal behavior tests revealed that HBOT intervention during PAC treatment led to the early alleviation of CIPN symptoms and inhibited CIPN deterioration. IF staining revealed that TLR4, TRPV1, and microglial activation were all upregulated in PAC-injected rats and exhibited early and significant downregulation in SHBOT-treated rats. This study is the first to demonstrate that the use of SHBOT during PAC treatment has potential for the early suppression of CIPN initiation and deterioration, indicating that it can alleviate CIPN symptoms and may reverse CIPN in patients undergoing systemic chemotherapy.