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
Painjournal_title
Painauthors
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 Ydoi
10.1097/j.pain.0000000000001986subject
Has Abstractpub_date
2020-11-01 00:00:00pages
2592-2602issue
11eissn
0304-3959issn
1872-6623pii
00006396-202011000-00016journal_volume
161pub_type
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