Thermal nociceptive properties of trigeminal afferent neurons in rats

Abstract

Background: Although nociceptive afferents innervating the body have been heavily studied form many years, much less attention has been paid to trigeminal afferent biology. In particular, very little is known concerning trigeminal nociceptor responses to heat, and almost nothing in the rat. This study uses a highly controlled and reproducible diode laser stimulator to investigate the activation of trigeminal afferents to noxious skin heating.

Results: The results of this experiment demonstrate that trigeminal thermonociceptors are distinct from themonociceptors innervating the limbs. Trigeminal nociceptors have considerably slower action potential conduction velocities and lower temperature thresholds than somatic afferent neurons. On the other hand, nociceptors innervating both tissue areas separate into those that respond to short pulse, high rate skin heating and those that respond to long pulse, low rate skin heating.

Conclusions: This paper provides the first description in the literature of the in vivo properties of thermonociceptors in rats. These finding of two separate populations aligns with the separation between C and A-delta thermonociceptors innervating the paw, but have significant differences in terms of temperature threshold and average conduction velocities. An understanding of the temperature response properties of afferent neurons innervating the paw skin have been critical in many mechanistic discoveries, some leading to new pain therapies. A clear understanding of trigeminal nociceptors may be similarly useful in the investigation of trigeminal pain mechanisms and potential therapies.

Figures

Figure 1

Receptive fields of recorded thermonociceptors. Receptive fields, first identified using mechanical stimuli, of all afferents recorded are shown as black dots near the eye.

Figure 2

Distribution of Conduction Velocities of Recorded Neurons. Number of afferents along the spectrum of conduction velocities, determined using delay to response to electrocutaneous stimulation of receptive fields are shown, along with the response specificity of those afferents.

Figure 3

Intensity Response Distribution. Afferent neurons demonstrated a relatively linear increase in number of action potentials ("spikes") evoked in response to increasing laser stimulus intensity. This observation was true both for short, high power and long, lower power laser diode stimuli.

Figure 4

Examples of responses of individual C fiber and A-delta nociceptor units to long or short laser pulses. A. Response of a C fiber nociceptor, A1 - action potential shape; A2 - lack of response to short pulse; A3 - response to long pulse; B. Response of an A-delta nociceptor, B1 - action potential shape; B2 - response to short pulse; B3 - lack of response to long pulse.

Figure 5

Skin Temperature Changes in Response to Laser Diode Stimulation. Surface skin temperature was measured using a high-speed thermal camera, and showed a decelerating increase in temperature produced by the constant intensity stimulus. This observation was true both for short, high power and long, lower power laser diode stimuli.

Figure 6

Relationship Between Threshold Temperature and Conduction Velocity. Temperature response thresholds were in a similar range for neurons that responded to either long or short pulses, however, all neurons that responded to both pulse types responded at lower temperatures to the long pulse.