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Inward currents in primary nociceptive neurons of the rat and pain sensations in humans elicited by infrared diode laser pulses

Greffrath, Wolfganga; Nemenov, Michael I.b; Schwarz, Stefana; Baumgärtner, Ulfa; Vogel, Hagena; Arendt-Nielsen, Larsc; Treede, Rolf-Detlefa,∗

doi: 10.1016/S0304-3959(02)00071-4
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Radiant heat is often used to study nociception in vivo. We now used infrared radiation generated by a diode laser stimulator (wavelength 980 nm) to investigate transduction mechanisms for noxious heat stimuli in acutely dissociated dorsal root ganglion (DRG) neurons of rats in vitro. The laser stimulator offered the unique opportunity to test whether the same stimuli also elicit pain sensations in humans. A specific heat-induced current (Iheat) was elicited in six of 13 small DRG neurons (diameter ≤30 μm) tested in the whole-cell configuration of the patch–clamp mode. Current responses in the seven heat-insensitive neurons were within the range explainable by the temperature dependence of the recording setup. Iheat was characterized by: (1) non-linearity of its amplitude during a suprathreshold heat ramp as well as with stimuli of increasing intensity with an estimated threshold of 42±1°C; (2) fast rise time and even faster decay time (t1/2=96.5±5.9 and 27.7±1.5 ms, respectively); and (3) rate dependence of its induction. All three heat-sensitive neurons tested were also sensitive to capsaicin. The mean threshold for the induction of Iheat was 2.8±0.3 J mm−2. The threshold for the induction of action potentials by depolarizing current pulses was significantly reduced after laser stimulation, suggesting a sensitization at the transformation stage. No such change was seen in heat-insensitive neurons that underwent the same heat stimuli. The same diode laser elicited pain sensations and laser-evoked potentials in human subjects. No significant differences were seen between the pain thresholds in hairy and in glabrous skin, probably due to the deep penetration of this laser radiation. The mean pain threshold for stimuli ≥200 ms in humans was 2.5±0.2 J mm−2 (n=11), and did not differ from the thresholds for the induction of Iheat in vitro. Our results indicate that Iheat in primary sensory neurons can be activated by infrared laser pulses that are painful in humans.

aInstitute of Physiology and Pathophysiology, Johannes Gutenberg University, Saarstrasse 21, D-55099 Mainz, Germany

bLaser Medical Center, I.P. Pavlov State Medical University, Lev Tolstoi Street 6/8, St. Petersburg 197022-1, Russia

cCenter for Sensory–Motor Interaction, Aalborg University, Fredrik Bajers Vej 7, D3, DK-9220 Aalborg, Denmark

Corresponding author. Tel.: +49-6131-392-5715; fax: +49-6131-392-5902

E-mail: treede@mail.uni-mainz.de

Submitted June 21, 2001; revised February 22, 2002; accepted March 1, 2002.

© 2002 Lippincott Williams & Wilkins, Inc.
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