Chronic neuropathic pain (NP) results from nerve dysfunction/lesion and affects approximately 20% of European adults. Due to its complexity NP is often misdiagnosed and inadequately treated. Nerve injury induces several changes including synthesis of neurotoxic mediators and prolonged transcription of the neurotoxic iNOS. These mediators are believed to contribute to peripheral and central neuronal sensitizations, and their levels have been shown to correlate with pain severity, suggesting their importance in nociception(1-3). We have previously shown that 1400W dihydrochloride, a highly specific iNOS inhibitor, reduced behavioural nociceptive responses in a NP model(4). The aim of the present study was to determine whether 1400W has an effect on inflammatory mediators, as well as having anti-nociceptive effects. Using the L5-Spinal Nerve Axotomy rodent model of NP in Wistar rats(5), carried out under anaesthesia (2% isoflurane), 1400W (20mg/kg) or its vehicle were administered to rats that were euthanized 10 days later. We investigate the effect of 1400W treatment on the expression of several inflammatory mediators, including TNF-α, MCP1, IL-1β, in injured L5 dorsal root ganglion (DRG) neurons. DRG immunohistochemical staining results showed no increase in TNF-α expression 10days post injury in any DRG cell population. MCP1 immunoreactivity was present in all DRG subpopulations, with the majority of small sized (<23µm) neurons being MCP1 positive. MCP1 levels increased with 1400W in both small and medium sized (23-32µm) DRG neurons (n=4; p<0.05, Fishers exact test used throughout). Small sized DRG neurons had the most intense IL-1β staining, and 1400W treatment resulted in an increase in the percentages of IL-1β positive small and medium sized neurons (n=4; p<0.05).Using a Multiplex ELISA, blood plasma obtained from all animals was analysed. Twelve inflammatory cytokines were simultaneously examined under uniform conditions. Plasma obtained from 1400W treated rats had increased levels of 4 of the cytokines analyzed; IL-1α (0.10±0.02 vs 0.16±0.01), IL-1β (0.35±0.04 vs 0.54±0.04), IL-10 (0.10±0.02 vs 0.15±0.01) and CCL5 (2.94±0.02 vs 3.02±0.02) (n=6, p<0.05, General linear model and Tukey posthoc test). These results suggest that although 1400W may alleviate pain by iNOS inhibition, its role as a potential anti-inflammatory agent is more complex. Analysis of blood plasma revealed that 1400W can successfully upregulate some anti-nociceptive mediators, such as IL-1α and IL-10, in contrast to its ability to increase levels of IL-1β, TNFα and CCL5. It is well known that several pro-inflammatory mediators are elevated in pain states but this study suggests that 1400W may function by increasing anti-nociceptive/pro-healing mediators (IL-1α and IL-10) to counteract and balance the neuroimmune response and in turn reduce neuronal hypersensitivity.