Topical axonal transport blocker vincristine prevents nerve injury-inducedspinal 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 perip heral nerve injury, was investigated on 31 rats: 20 with chronic constricti on 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 s ciatic nerve before ligation (Vin(+)); in the remaining 5 rats the nerve wa s 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 (P O) weeks. In the CCI Vin(-) rats, the neurons showed increased spontaneous activity and hyperresponsiveness to noxious stimulus with prolonged afterdi scharges, events considered to signal central neuron sensitization. In the CCI Vin(+) rats, the neuronal spontaneous and stimulated activity values we re significantly lower (p < 0.001) than in the CCI Vin(-) rats being compar able to normal values, In sham Vin(+) and Vin(-) rats, the neuronal activit ies 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.