Reilly, JM; (2013) Expression and function of Kv7/M-channels within the peripheral nociceptive pathway. Doctoral thesis (PhD), UCL (University College London).

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Abstract

Novel targets for the treatment of pain are continually being sought. These new targets may lie within the pain pathway, which facilitates the detection, transmission and perception of pain and include ion channels which control neuronal excitability such as Kv7/M-channels which have been implicated in the control of neuronal excitability in peripheral neurons. The aim of this work was to determine the expression of Kv7/M-channels in the peripheral components of the nociceptive sensory pathway and to investigate aspects of their functional significance. Immunohistochemical techniques to determine the localisation of the channel were completed using antibodies to the Kv7.2 subunit of the channel and to various neuronal makers. Immunoreactivity to Kv7.2 was detected in a variety of DRG sensory neurons and peripheral sensory nerve fibres; including small nociceptive neurons. Immunoreactivity to Kv7.2 was also detected diffusely along unmyelinated fibres within the vagus nerve. Electrophysiological measurement found that these fibres could be hyperpolarised in a XE991 sensitive manner by retigabine. The Kv7/M-channel was also identified in keratinocytes by immunoreactivity for Kv7.2, RT-PCR, electrophysiological recordings and a potentiated induced release of ATP by retigabine was observed, this effect was blocked by XE991. These new neuroanatomical locations for M-channel are helpful in the interpretation of functional studies on the role of M-channels in regulating peripheral nociception. The localisation of the channel in presumably non-nociceptive fibres raises additional possibilities regarding their role in other forms of sensation. The functional studies also expand potential roles for M-channels to the regulation of C-fibre activity and also to aspects of keratinocyte function. These results also raise the question of how far the effects of retigabine (and other M-channel enhancers) observed in other studies are due to peripheral actions.

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