Analysis of nociceptive system in pathologic conditions

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The polymodal receptor, one of the peripheral pain receptors, is involved in acute and chronic inflammatory pain. Its excitability is able to be modified by inflammation-related substances, changes in tissue temperature, etc. Under acute or chronic inflammatory processes, inflammatory mediators such as BK,PGs, 5-HT are suggested to be released in inflammatory region. So far, it has been impossible to record receptor activities from free nerve endings because of their small size. At present we have a good possibility to clarify the mechanisms of action of mediators on nociceptor membrane or intracellular dynamics using intracellular recording and patch clamp techniques from dorsal root ganglion cells (DRG cells), since we have demonstrated that the membrane characteristics and sensitivity to capsaicin (CAP) of DRG cells are closely resemble those of receptor membrane.In this project we clarified the effect of BK (10muM) on cultured DRG cells from intact rat, using of neurophysiological techniques. The results are followed :(1) In cultured cell within 24 hr.with and without NGF,the BK did not affect membrane potential, membrane input resistance and membrane current of CAP-sensitive cells.(2) Cultured CAP-sensitive cells more than 48 hr.were depolarized by the BK with action potentials. In the cultured cells with NGF the depolarization by the BK were much bigger than one of cultured cells without NGF.For next steps, we will observe PGs and 5-HT effects on cultured DRG cells and they will be compared with results obtained from rats under acute or chronic pathological conditions.