Inflammation-induced changes in BKCa currents in cutaneous dorsal root ganglion neurons from the adult rat

Inflammation-induced sensitization of small diameter cutaneous neurons was associated with an increase in action potential duration and rate of decay of the afterhyperpolarization. However, no changes in voltage-gated K+ currents were detected. In contrast, Ca2+ modulated iberiotoxin sensitive and paxilline sensitive K+ (BKCa) currents were significantly smaller in small diameter IB4+ neurons. This decrease in current was not associated with a detectable change in total protein levels of the BKCa channel α or β subunits. Single cell PCR analysis revealed a significant change in the pattern of expression of α subunit splice variants and β subunits that were consistent, at least in part, with inflammation-induced changes in the biophysical properties of BKCa currents in cutaneous neurons.Results of this study provide additional support for the conclusion that it may be possible, if not necessary to selectively treat pain arising from specific body regions. Because a decrease in BKCa current appears to contribute to the inflammation-induced sensitization of cutaneous afferents, BKCa channel openers may be effective for the treatment of inflammatory pain.Peripheral inflammation is associated with pain and hyperalgesia that reflects, at least in part, the sensitization of primary afferents innervating the site of inflammation [1]. This increase in excitability reflects both acute (i.e., phosphorylation) and persistent (i.e., transcription) changes in a variety of ion channels [1] that control afferent excitability. Results from a series of studies on afferents innervating glabrous skin of the rat suggest that the impact of inflammation on the underlying mechanisms of sensitization is complex. Analysis of afferents in vivo indicate that the inflammation-induced increase in excitability is associated with changes in axon conduction velocity, [2] as well as changes in the action potential waveform invading the cell soma in a subpopulation of afferents [3]. Evidence from a r