0000000000133699
AUTHOR
Timo Kirschstein
Changes in cytosolic calcium in response to noxious heat and their relationship to vanilloid receptors in rat dorsal root ganglion neurons.
Heat transduction mechanisms in primary nociceptive afferents have been suggested to involve a vanilloid receptor channel with high calcium permeability. To characterize the changes in free cytosolic calcium evoked by noxious heat stimuli (< or =51 degrees C, 10s), we performed microfluorometric measurements in acutely dissociated small dorsal root ganglion neurons (< or =32.5 microm) of adult rats using the dye FURA-2. Only neurons that responded with a reversible increase in intracellular calcium to high potassium were evaluated. Heat-induced calcium transients (exceeding mean + 3S.D. of the temperature dependence of the dye) were found in 66 of 105 neurons. These transients increased non…
Coexpression of heat-evoked and capsaicin-evoked inward currents in acutely dissociated rat dorsal root ganglion neurons.
Noxious heat is able to activate heat-sensitive nociceptors in the skin very rapidly, but little is known about the mechanisms by which heat is transduced. We used the whole-cell patch-clamp technique to study the effects of noxious heat and capsaicin on freshly dissociated rat dorsal root ganglion neurons in vitro. Using temperatures between 41 degrees C and 53 degrees C, 8 of 19 small neurons (phior = 30 microm) exhibited a heat-evoked inward current. All heat-sensitive neurons tested were also capsaicin-sensitive. Moreover, the heat response tended to be enhanced after capsaicin (360 +/- 150 pA versus 125 +/- 45 pA, P0.1, n = 7). Two of five heat-insensitive neurons were excited by capsa…
Acetylsalicylic acid reduces heat responses in rat nociceptive primary sensory neurons – evidence for a new mechanism of action
Acetylsalicylic acid (ASA) is thought to exert its peripheral analgesic effects via inhibition of cyclooxygenase. We now studied the effects of ASA on heat responses in primary nociceptive neurons by whole-cell patch-clamp and calcium microfluorimetry experiments. Heat-evoked inward currents in acutely dissociated rat dorsal root ganglion neurons were significantly reduced by ASA in a dose-dependent and reversible manner (IC(50) 375 nM, Hill slope -2.2, maximum effect 55%). Heat-evoked calcium transients (measured with FURA-2) were reversibly reduced by 53+/-14% (P0.05) by co-application of 1 microM ASA. The low IC(50) value, the rapid occurrence, and the reversibility of the observed effec…
Inhibition of rapid heat responses in nociceptive primary sensory neurons of rats by vanilloid receptor antagonists.
Recent studies demonstrated that heat-sensitive nociceptive primary sensory neurons respond to the vanilloid receptor (VR) agonist capsaicin, and the first cloned VR is a heat-sensitive ion channel. Therefore we studied to what extent heat-evoked currents in nociceptive dorsal root ganglion (DRG) neurons can be attributed to the activation of native vanilloid receptors. Heat-evoked currents were investigated in 89 neurons acutely dissociated from adult rat DRGs as models for their own terminals using the whole cell patch-clamp technique. Locally applied heated extracellular solution (effective temperature ∼53°C) rapidly activated reversible and reproducible inward currents in 80% (62/80) o…