Topical axonal transport blocker vincristine prevents nerve injury-induced spinal neuron sensitization in rats

The effect of vincristine (Vin, a fast axonal transport blocker) to prevent any alteration in the excitability of dorsal horn neurons, following peripheral nerve injury, was investigated on 31 rats: 20 with chronic constriction injury (CCI) of the sciatic nerve and 11 sham preparations. In 15 of the 20 CCI rats, a small piece of gelfoam soaked with Vin was applied to the sciatic nerve before ligation (Vin+); in the remaining 5 rats the nerve was ligated without Vin (Vin-). The 11 sham rats were 7 Vin+ and 4 Vin-. The dorsal horn neuronal activity was recorded after 2-3 postoperative (PO) weeks. In the CCI Vin- rats, the neurons showed increased spontaneous activity and hyperresponsiveness to noxious stimulus with prolonged afterdischarges, events considered to signal central neuron sensitization. In the CCI Vin+ rats, the neuronal spontaneous and stimulated activity values were significantly lower (p < 0.001) than in the CCI Vin- rats being comparable to normal values. In sham Vin+ and Vin- rats, the neuronal activities had normal values. Given the crucial role attributed to central neuron sensitization for the development of neuropathic pain, the possibility that vincristine, by blocking the axonal transport, exerts a preventive action on this syndrome is discussed.