DynChomiR

The proposed project Dynamic regulation of cholinergic circuits and associated microRNAs in the prefrontal cortex of a murine neuropathic pain model DynChomiR will investigate the role of the neurotransmitter acetylcholine in the medial prefrontal cortex during the chronification of pain. Chronic neuropathic pain constitutes a serious public health problem with major impacts on the patients quality of life, but the underlying pathogenesis is still incompletely understood and diagnostic and treatment options are unsatisfactory. Among different brain regions, the medial prefrontal cortex is known to be involved in pain processing. We will investigate which of the different regions that send information through cholinergic nerve fibers to the medial prefrontal cortex are activated by a painful stimulus, and how this affects the release of acetylcholine and the expression of cholinergic receptors in the prefrontal cortex. These data will be further complemented by electrophysiological recordings of neuronal network activity and neuron function in the brain. In an entirely novel approach we will then focus on the expression changes of a sub-group of non-coding RNAs, the microRNAs, which have recently been found to act as novel regulators of biomedical processes in many tissues, including the brain. Using state-of-the-art molecular biology and bioinformatics, mRNA-microRNA interactions will be identified. It is anticipated that microRNAs regulate the circuitry in mPFC circuits during the chronification of neuropathic pain. Finally, DynChomiR will contribute to understand the mechanisms underlying the generally accepted difference in pain sensitivity and intensity of pain perception between men and women. The DynChomiR project will uncover the importance of a particular brain region and the biological role of microRNAs in pain syndromes. Innovative novel concepts, microRNA targets and pathways will become available and will be shared with other scientific disciplines, with the overall aim to identify new therapeutic options for the treatment of neuropathic pain and possible relevance for other neurological diseases.