The Fine Tuning of Pain Thresholds: A Sophisticated Double Alarm System

Two distinctive features characterize the way in which sensations including pain, are evoked by heat: (1) a thermal stimulus is always progressive; (2) a painful stimulus activates two different types of nociceptors, connected to peripheral afferent fibers with medium and slow conduction velocities, namely Aδ- and C-fibers. In the light of a recent study in the rat, our objective was to develop an experimental paradigm in humans, based on the joint analysis of the stimulus and the response of the subject, to measure the thermal thresholds and latencies of pain elicited by Aδ- and C-fibers. For comparison, the same approach was applied to the sensation of warmth elicited by thermoreceptors. A CO2 laser beam raised the temperature of the skin filmed by an infrared camera. The subject stopped the beam when he/she perceived pain. The thermal images were analyzed to provide four variables: true thresholds and latencies of pain triggered by heat via Aδ- and C-fibers. The psychophysical threshold of pain triggered by Aδ-fibers was always higher (2.5–3°C) than that triggered by C-fibers. The initial skin temperature did not influence these thresholds. The mean conduction velocities of the corresponding fibers were 13 and 0.8 m/s, respectively. The triggering of pain either by C- or by Aδ-fibers was piloted by several factors including the low/high rate of stimulation, the low/high base temperature of the skin, the short/long peripheral nerve path and some pharmacological manipulations (e.g. Capsaicin). Warming a large skin area increased the pain thresholds. Considering the warmth detection gave a different picture: the threshold was strongly influenced by the initial skin temperature and the subjects detected an average variation of 2.7°C, whatever the initial temperature. This is the first time that thresholds and latencies for pain elicited by both Aδ- and C-fibers from a given body region have been measured in the same experimental run. Such an approach illustrates the role of nociception as a “double level” and “double release” alarm system based on level detectors. By contrast, warmth detection was found to be based on difference detectors. It is hypothesized that pain results from a CNS build-up process resulting from population coding and strongly influenced by the background temperatures surrounding at large the stimulation site. We propose an alternative solution to the conventional methods that only measure a single “threshold of pain”, without knowing which of the two systems is involved

Peripheral and Central Determinants of a Nociceptive Reaction: An Approach to Psychophysics in the Rat

BACKGROUND: The quantitative end-point for many behavioral tests of nociception is the reaction time, i.e. the time lapse between the beginning of the application of a stimulus, e.g. heat, and the evoked response. Since it is technically impossible to heat the skin instantaneously by conventional means, the question of the significance of the reaction time to radiant heat remains open. We developed a theoretical framework, a related experimental paradigm and a model to analyze in psychophysical terms the "tail-flick" responses of rats to random variations of noxious radiant heat. METHODOLOGY/PRINCIPAL FINDINGS: A CO(2) laser was used to avoid the drawbacks associated with standard methods of thermal stimulation. Heating of the skin was recorded with an infrared camera and was stopped by the reaction of the animal. For the first time, we define and determine two key descriptors of the behavioral response, namely the behavioral threshold (Tbeta) and the behavioral latency (Lbeta). By employing more than one site of stimulation, the paradigm allows determination of the conduction velocity of the peripheral fibers that trigger the response (V) and an estimation of the latency (Ld) of the central decision-making process. Ld (approximately 130 ms) is unaffected by ambient or skin temperature changes that affect the behavioral threshold (approximately 42.2-44.9 degrees C in the 20-30 degrees C range), behavioral latency (<500 ms), and the conduction velocity of the peripheral fibers that trigger the response (approximately 0.35-0.76 m/s in the 20-30 degrees C range). We propose a simple model that is verified experimentally and that computes the variations in the so-called "tail-flick latency" (TFL) caused by changes in either the power of the radiant heat source, the initial temperature of the skin, or the site of stimulation along the tail. CONCLUSIONS/SIGNIFICANCE: This approach enables the behavioral determinations of latent psychophysical (Tbeta, Lbeta, Ld) and neurophysiological (V) variables that have been previously inaccessible with conventional methods. Such an approach satisfies the repeated requests for improving nociceptive tests and offers a potentially heuristic progress for studying nociceptive behavior on more firm physiological and psychophysical grounds. The validity of using a reaction time of a behavioral response to an increasing heat stimulus as a "pain index" is challenged. This is illustrated by the predicted temperature-dependent variations of the behavioral TFL elicited by spontaneous variations of the temperature of the tail for thermoregulation

Biological inflammatory markers mediate the effect of preoperative pain-related behaviours on postoperative analgesics requirements

Peer reviewedPublisher PD

Thermal Detection Thresholds of Aδ- and C-Fibre Afferents Activated by Brief CO2 Laser Pulses Applied onto the Human Hairy Skin

Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO2 laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C) and C-fibres (39.8±1.7°C). Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively