Peripheral nerve injury and sensitization underlie pain associated with oral cancer perineural invasion. Issue 11 (November 2020)

• Record Type: Journal Article
• Authors: Salvo, Elizabeth; Campana, Wendy M.; Scheff, Nicole N.; Nguyen, Tu Huu; Jeong, Se-hee; Wall, Ian; Wu, Angie K.; Zhang, Susanna; Kim, Hyesung; Bhattacharya, Aditi; Janal, Malvin N.; Liu, Cheng; Albertson, Donna G.; Schmidt, Brian L.; Dolan, John C.; Schmidt, Robert E.; Boada, M. Danilo; Ye, Yi
• Is Part Of: Pain. Volume 161:Issue 11(2020)
• Publication Date: 2020-11
• Subjects: Oral cancer pain -- Perineural invasion -- Nerve injury -- Sensitization -- Nociceptors -- HTMRs -- LTMRs -- Schwann cells; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000001986
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Abstract: Cancer invading into nerves, termed perineural invasion (PNI), is associated with pain. Here, we show that oral cancer patients with PNI report greater spontaneous pain and mechanical allodynia compared with patients without PNI, suggesting that unique mechanisms drive PNI-induced pain. We studied the impact of PNI on peripheral nerve physiology and anatomy using a murine sciatic nerve PNI model. Mice with PNI exhibited spontaneous nociception and mechanical allodynia. Perineural invasion induced afterdischarge in A high-threshold mechanoreceptors (HTMRs), mechanical sensitization (ie, decreased mechanical thresholds) in both A and C HTMRs, and mechanical desensitization in low-threshold mechanoreceptors. Perineural invasion resulted in nerve damage, including axon loss, myelin damage, and axon degeneration. Electrophysiological evidence of nerve injury included decreased conduction velocity, and increased percentage of both mechanically insensitive and electrically unexcitable neurons. We conclude that PNI-induced pain is driven by nerve injury and peripheral sensitization in HTMRs. Abstract : Supplemental Digital Content is Available in the Text.We report that oral cancer perineural invasion leads to nerve injury and nociceptor sensitization in mice, contributing to higher levels of pain in patients with perineural invasion.