Peripheral nerve injury and sensitization underlie pain associated with oral cancer perineural invasion
Year: 2020
Type: article
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.
Source: Pain
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Schwann cell activation in oral cancer perineurial invasion and neuropathic pain, Schwann Cell Activation and Oral Cancer Pain, Protease/PAR2/TRPV4 Axis and Oral Cancer Pain, The Role of Proteases and Peptides in Cancer Pain, Predictive Markers for Oral Carcinoma Metastasis, FISH assay identifying oral cancer patients at low risk of lymph node metastasis, Genome amplification and dysbiosis in tongue cancer, Cancer Center Support Grant
OpenAlex ID: W3042350908