Studies of peripheral nerve inflammation (neuritis) suggest that some symptoms of neuropathic pain can be generated from inflamed but otherwise uninjured axons. We have previously inferred a role for inflammation-induced axonal transport disruption in the underlying mechanisms. In the present study, we have investigated the development of sensory hypersensitivities following vinblastine-induced axonal transport disruption. Similar to neuritis, locally applied .1 mM vinblastine caused the rapid development of mechanical hypersensitivity within the first week postsurgery. The same animals did not develop heat hypersensitivity. Because aberrant firing from primary sensory neurons is considered necessary to drive spinal mechanisms that lead to hypersensitivities, the levels of ongoing activity and axonal mechanical sensitivity were examined. Recordings from A- and C-fiber neurons did not reveal differences in the levels of ongoing activity between vinblastine-treated (<5.8%) and saline-treated control animals (<4.6%). However, 28% of C-fiber axons were mechanically sensitive at the vinblastine treatment site. Using kinesin immunohistochemistry, we confirmed a reduction of anterograde axonal transport in vinblastine-treated and neuritis animals. In summary, this study has revealed an alternative pain model, which may be relevant to conditions that are not accompanied by frank nerve injury.

In this study, we expand our previous reports and demonstrate that focal reduced axonal transport causes distal mechanical hypersensitivity considered consistent with neuropathic pain but in the absence of nerve injury. These findings may inform pain conditions that have a neural inflammatory component.