Objective
Unpleasant sensory experiences and burning pain are frequent complications of diabetes mellitus (DM). Degenerative changes of primary sensory neurones (PSNs) caused by metabolic alterations and absence of insulin-mediated neurotrophic effects contribute to the development of these symptoms. The manifestation of type 2 DM is often preceded by impairment of glucose utilisation and a compensatory hyperinsulinaemia. Despite the lack of metabolic disorders dysfunctions of the thermo-nociception are still present during this period indicating that hyperinsulinaemia might influence the activity of heat sensitive PSNs. Recently we found that insulin activate a subpopulation of PSNs expressing the heat transducer molecule Transient Receptor Potential Vanilloid 1 (T RPV1) ion channel. Therefore we intend to study the long term effects of hyperinsulinaemia on the neurochemical phenotype and sensory functions of PSNs. Effects of hyperinsulinaemia will be studied on Zucker diabetic fatty (ZDF) rats the animal model of ty pe 2 DM.
Expression of TRPV1 and other neurochemical markers of nociceptive neurones will be investigated by morphological and biochemical methods on PSN cultures incubated in the presence of insulin and in sensory ganglia of ZDF rats. Functional alterations in primary nociceptors chronically exposed to insulin will be assessed by measurement of neuronal responses evoked by noxious chemical and thermal stimuli. The sensory afferent- and the vasoregulatory efferent functions of cutaneous and visceral nociceptors as well as the development of the inflammatory heat hyperalgesia will be investigated in ZDF rats using behavioural tests and in vivo measurements of sensory nerve-mediated vascular reactions. These experiments will provide new information on the role of hyperinsulinaemia in the development of sensory dysfunctions present in the type 2 diabetes and clarify the pathological significance of the insulin mediated modulation of nociceptor activity.
Fields of science (EuroSciVoc)
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Topic(s)
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Call for proposal
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FP6-2004-MOBILITY-11
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
SZEGED
Hungary
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