Neuropathic pain is a severe health problem, which is further complicated by the lack of effective therapy. Search for new treatments has recently focused on ion channel candidates, since expression and activity of many ion channels relevant to pain signalling have been found altered following nerve injury. There is compelling evidence for the role of non-inactivating, subthreshold Kv7 (KCNQ, ‘M type’) potassium channels in pain transmission, as the membrane excitability of small nociceptive DRG neurons increases following pharmacological or receptor-induced inhibition of M current (Passmore et al, 2003; Linley et al, 2008). Immunohistochemistry in adult rat DRG revealed that Kv7.2 protein is expressed within subpopulations of CGRP-, IB4- and TRPV1-positive neurons. Behavioural tests demonstrated that acute in vivo inhibition of M channels expressed in nociceptive neuronal terminals of rat hindpaw induced by the intraplantar injection of specific Kv7 blocker, XE991 (10 nmoles/site), resulted in spontaneous nocifensive behaviour not observed in rats injected with vehicle. We next studied a possible role of M channels in the development of chronic pain following peripheral nerve injury. To this end we investigated the expression of KCNQ2 in the DRG and sciatic nerve neuroma of Partial Sciatic Nerve Ligation (PSNL) operated rats. Under general anesthesia with 2% isoflurane, the nerve was exposed, partially ligated and sectioned. Real-time RT-PCR experiments revealed that the level of KCNQ2 mRNA within PSNL injured rat L4 and L5 DRG was significantly decreased 30 days following nerve injury in comparison to sham operated rats (mean±s.e.m, 0.23±0.05 to 0.09±0.03 relative to housekeeping gene U6, n=6, P = 0.03 using students t-test). We also studied the expression of the Repressor Element 1-Silencing Transcription factor (REST), a transcription factor that can bind to KCNQ DNA in vitro and reduce M channel expression in cultured DRG neurons (Ooi et al, 2009). REST mRNA expression was increased in the L4 and L5 DRG of PSNL injured rats in comparison to sham REST expression (0.008±0.002 to 0.019±0.004 relative to U6, n = 6, P = 0.007). In addition KCNQ2 mRNA was decreased in the ipsilateral nerve neuroma of PSNL injured rats in comparison to sham sciatic nerve KCNQ2 mRNA expression (1×10^-4±0.4×10^-4 to 1×10^-5±0.3×10^-5 relative to U6, n = 6, P = 0.04). Preliminary immunohistochemical analysis of PSNL rat L4 DRG showed a decrease in Kv7.2 protein expression 15 days following injury in comparison to sham operated rats. In sum our data suggest that transcriptional down-regulation of M channel expression in nociceptive sensory neurones can contribute to increased excitability of peripheral nerves induced by nerve injury.