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We have previously shown that nerve inflammation (neuritis) and transient vinblastine application lead to axonal mechanical sensitivity in nociceptors innervating deep structures. We have also shown that these treatments reduce axonal transport, and proposed that this leads to functional accumulation of mechanically sensitive channels in the affected part of the axons. While informing the etiology of mechanically induced pain, axonal mechanical sensitivity does not address the common report of ongoing radiating pain during neuritis, which could be secondary to the provocation of axonal chemical sensitivity. We proposed that neuritis and vinblastine application would induce sensitivities to noxious chemicals, and that the number of chemo-sensitive channels would be increased at the affected site. In adult female rats, nerves were either untreated, or treated with complete Freund’s adjuvant (to induce neuritis) or vinblastine. After 3-7 days, dorsal root teased fiber recordings were taken from Group IV neurons with axons within the sciatic nerve. Sciatic nerves were injected intraneurally with a combination of noxious inflammatory chemicals. While no normal sciatic axons responded to this stimulus, 80% and 38% of axons responded in the neuritis and vinblastine groups, respectively. In separate experiments, sciatic nerves were partially ligated and treated with complete Freund’s adjuvant or vinblastine (with controls), and after 3-5 days were immunolabeled for the histamine 3 receptor. The results supported that both neuritis and vinblastine treatment reduce transport of the histamine 3 receptor. The finding that nociceptor axons can develop ectopic chemical sensitivity is consistent with ongoing radiating pain due to nerve inflammation.


This is the manuscript version of an article accepted for publication in Journal of Neurophysiology. This version will become available for use 12 months after publication in the journal.

Originally published:

Govea RM, Barbe MF, Bove GM. Group IV nociceptors develop axonal chemical sensitivity during neuritis and following treatment of the sciatic nerve with vinblastine. Journal of Neurophysiology, July 2017, jn.00395.2017; DOI: 10.1152/jn.00395.2017

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