Neuritis and Vinblastine-induced Axonal Transport Disruption Lead to Signs of Altered Dorsal Horn Excitability

Background: Many patients with neuropathic pain present without signs of nerve injury on routine clinical examination. Some of these patients may have inflamed peripheral nerves (neuritis). In this study, we have examined whether neuritis causes changes within the dorsal horn that may contribute to a central pain mechanism. Comparisons have been made to a model of axonal transport disruption induced using vinblastine, since neuritis disrupts such processes.

Results: At the peak of cutaneous hypersensitivities, recordings from wide dynamic range neurons revealed increases in wind-up following neuritis but not vinblastine treatment. Ongoing activity from these neurons was unchanged. Vinblastine treatment caused a reduction in the responses of wide dynamic range neurons to noxious mechanical stimulation of the receptive field. The response of neurons to innocuous mechanical stimulation was also reduced in wide dynamic range neurons that were at a depth ≥550 µm following vinblastine treatment. An examination of the superficial dorsal horn revealed an increase in c-Fos-positive neurons in both groups following electrical stimulation of the sciatic nerve. The area of dorsal horn expressing substance P was also decreased following vinblastine treatment.

Conclusion: These findings indicate that a minor nerve insult, such as neuritis, can lead to changes within the dorsal horn that are consistent with a central neuropathic pain mechanism.