Heat-Induced Action Potential Discharges in Nociceptive Primary Sensory Neurons of Rats

Abstract

Greffrath W, Schwarz ST, Bü sselberg D, Treede R-D. Heatinduced action potential discharges in nociceptive primary sensory neurons of rats. J Neurophysiol 102: 424 -436, 2009. First published May 13, 2009 doi:10.1152/jn.90916.2008. Although several transducer molecules for noxious stimuli have been identified, little is known about the transformation of the resulting generator currents into action potentials (APs). Therefore we investigated the transformation process for stepped noxious heat stimuli (42-47°C, 3-s duration) into membrane potential changes and subsequent AP discharges using the somata of acutely dissociated small dorsal root ganglion (DRG) neurons (diameter Յ32.5 m) of adult rats as a model for their own peripheral terminals. Three types of heat-induced membrane potential changes were differentiated: type 1, heat-induced AP discharges (ϳ37% of the neurons); type 2, heat-induced membrane depolarization (40%); and type 3, responses not exceeding those of switching the superfusion (23%). Warming neurons from room temperature to 35°C increased their background conductance, nearly doubled the AP threshold current, and led to smaller and narrower APs. Adaptation of heat-induced AP discharges was seen in about half of the type 1 neurons. The remaining half displayed accelerating discharges to both heat stimuli and depolarizing current injection. Repeated heat stimulation induced marked suppression of AP discharges. Under rapid calcium buffering using BAPTA, repolarization of heat-induced APs stopped at a plateau potential slowly decreasing from ϩ16.5 Ϯ 2.9 to Ϫ2.2 Ϯ 5.5 mV, resulting in no further AP discharges. This study demonstrates that heat-induced AP discharges can be elicited in the soma of a subgroup of DRG neurons. These discharges display suppression on repetitive stimulation, but either adaptation or sensitization during prolonged stimuli. AP threshold and AP shape during these discharges suggest temperature dependence of background conductance and repolarizing currents.

Chronic Spontaneous Activity Generated in the Somata of Primary Nociceptors Is Associated with Pain-Related Behavior after Spinal Cord Injury

“…Recordings were made at 22°C rather than body temperature to permit direct comparisons to subsequent studies of underlying biophysical mechanisms; the slower kinetics of conductances at this temperature facilitate the experimental separation of ionic currents. Little is known about the temperature dependence of spontaneous activity (SA) in nociceptive DRG neurons, but these neurons exhibit complex temperature-dependent effects on other excitability properties (e.g., Greffrath et al, 2009). While still under voltage clamp, the Clampex Membrane Test program (Molecular Devices) was used to determine C m and membrane resistance, R m , during a 10 ms, 5 mV depolarizing pulse from a holding potential of −60 mV.…”

The capsaicin receptor TRPV1 is the first line defense protecting from acute non damaging heat: a translational approach

“…[21] for TRPV3). In heat activated HEK cells, calcium flux through TRPV1 can be assumed to be the dominant source of intracellular calcium transients, whereas in DRG neurons calcium mainly flows through voltage gated calcium channels (75% [18]) that are activated by action potentials, elicited by depolarization of the neurons via TRPV1 [20]. In our data, threshold energies did not differ significantly between DRG neurons and HEK cells, the similarity in strength-duration curves in the range of 2-10 ms suggests no major differences in thermal gating kinetics of native rat TRPV1 in DRG neurons and heterologously expressing HEK cells.…”

“…Human heat pain displays rapid habituation reflecting peripheral fatigue when stimulation is restricted to the same nociceptive neurons [17]. Distinct tachyphylaxis to repetitive heat applied by either diode lasers or heated superfusion is known to occur in TRPV1-transfected HEK cells [55], generator currents as well as action potential discharges of neurons [20,52] and nociceptive Aδ-and C-fibers in monkey and humans [2,32,45,58]. Heterologous expression of TRPV1 inserted this type of pain memory into primarily non-excitable HEK cells.…”

Morphological and functional diversity of first-order somatosensory neurons

“…The classification criteria described above are based on the response to a prolonged depolarizing current injection. It is important to note that differences in firing patterns (phasic versus tonic) are also observed in the cell bodies of DRG neurons in response to sustained natural stimuli, such as reduced pH (Immke and McCleskey 2001;Ditting et al 2009), changes in temperature (Greffrath et al 2009), and mechanical stimulus (Viatchenko-Karpinski and Gu 2016).…”