Peripheral nerve injury and sensitization underlie pain associated with oral cancer perineural invasion.

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.

journal_name

Pain

journal_title

Pain

authors

Salvo E,Campana WM,Scheff NN,Nguyen TH,Jeong SH,Wall I,Wu AK,Zhang S,Kim H,Bhattacharya A,Janal MN,Liu C,Albertson DG,Schmidt BL,Dolan JC,Schmidt RE,Boada MD,Ye Y

doi

10.1097/j.pain.0000000000001986

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

2592-2602

issue

11

eissn

0304-3959

issn

1872-6623

pii

00006396-202011000-00016

journal_volume

161

pub_type

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