In primary sensory neurons, ion channel components necessary for sensory transduction are conveyed by axoplasmic transport from the dorsal root ganglia to the peripheral terminals for insertion into the membrane. We hypothesised that disruption of axoplasmic transport by local nerve inflammation may cause accumulation of these channels at the inflamed site, leading to a hotspot of axonal hyperexcitability. The development of spontaneous firing in sensory axons at the site of hyperexcitability may induce central changes that drive symptoms such as allodynia in patients with neuropathic pain. Consistent with this hypothesis, the blockade of axoplasmic transport by the anti-mitotic agent vinblastine (0.1 mM) causes nociceptors to become mechanically sensitive at the site of application in the absence of axonal degeneration (Dilley & Bove, 2008). Here, we examine the development of cutaneous hypersensitivity (allodynia and hyperalgesia) following the local application of vinblastine to rat sciatic nerves. The left sciatic nerve was exposed in anaesthetised adult male Sprague Dawley rats (isoflurane, 1.75% in O2) and treated with 0.1mM vinblastine (n=6) or vehicle (saline; n=6) as previously described (Dilley & Bove, 2008). Untreated animals (n=6) were also tested. Pre-surgery and daily up to 11 days post-surgery, ipsilateral and contralateral hind paws were tested for signs of allodynia using von Frey filaments of increasing stiffness. The lowest filament to produce a rapid foot withdrawal was considered the withdrawal threshold. Heat sensitivity was also tested using a radiant heat source (Hargreaves’ method). Latency to foot withdrawal was recorded. In vehicle and untreated groups there were no signs of mechanical allodynia. In the vinblastine group, mechanical allodynia developed ipsilaterally following surgery, peaking on day 4 (mean withdrawal threshold: pre-surgery = 12.5g (0.7 SEM); day 4 = 5.3g (0.7 SEM); p<0.05 vs. pre-surgery, contralateral and control groups, T test). By day 11, there were signs of recovery (mean = 11.3g (2.3 SEM)). However vinblastine treatment did not induce heat hyperalgesia (mean withdrawal latency: pre-surgery = 16.6s (1.0 SEM); day 4 = 15.2s (1.5 SEM); p>0.5 vs. pre-surgery, contralateral and control groups, T test). In summary, mid-axonal axoplasmic transport disruption using vinblastine causes development of mechanical allodynia, as seen in other models of neuropathic pain. Thus, the disruption of axoplasmic transport may contribute to symptoms in patients with neuropathic pain. Consistent with this hypothesis, electrophysiological recordings from isolated C-fibre neurons in the vinblastine model have revealed evidence of spontaneous activity. These changes may also be relevant to neuropathies induced by chemotherapy.