The development and maintenance of chronic inflammatory and neuropathic pain are often associated with functional changes in the excitability of peripheral afferents. Electrophysiological recordings on dissociated cells offer the greatest opportunity to study the mechanisms responsible for events that lead to changes in excitability. However, specific nociceptive populations in the DRG are not readily identifiable in vitro. Capsaicin sensitivity can broadly identify heat sensitive nociceptors but there is no means to readily identify subpopulation of capsaicin sensitive or capsaicin insensitive (CI) nociceptive populations of the DRG. In vivo, it has been shown that afterhyperpolarization duration (AHP) can distinguish nociceptive subpopulations from non-nociceptive populations. In our proposed investigations we will determine whether AHP distributions, observed in vivo, are maintained in vitro, and we will specifically examine and contrast the properties of CI cells with capsaicin insensitive groups with different AHPs. The experiments described we will use whole cell patch recordings on adult dissociated DRG cells. The studies have the following goals: 1) Characterization and modulation of proton activated currents in CI cells, including: an ASIC/DRASIC form of proton activated current and a TASK-like (TASK-1) current; 2) An examination of the reactivity of CI cells to heat and cold; 3) Determination of the histochemical phenotype of CI cells (IB4, SP, CGRP); and 4) To contrast the electrophysiological and immunohistochemical properties of CI and capsaicin sensitive cells.
