Single C nociceptor responses and psychophysical parameters of evoked pain: effect of rate of rise of heat stimuli in humans.

Abstract

1. Effects of rate of rise of temperature stimuli applied to skin on (i) unitary receptor threshold and frequency response often single C nociceptors, and (ii) on magnitude and reaction times of evoked pain were studied in fifteen healthy human volunteers. 2. Temperature ramps of 32 to 45 or 47 degrees C were applied at three consistent rates of rise to receptive fields of C nociceptors in dorsum of foot (n = 9) or hand (n = 1). For rates of rise of 0.3, 2.0 and 6.0 degrees C/s, mean receptor threshold for heat was remarkably uniform: 41.5 +/- 0.57, 41.5 +/- 0.61 and 41.9 +/- 0.71 degrees C respectively. 3. The mean discharge rate of the ten cutaneous C nociceptors increased with rate of rise of temperature stimuli: 1.22 +/- 0.13, 4.57 +/- 0.49 and 13.45 +/- 0.71 impulses/s, respectively, for stimulus temperature rates of 0.3, 2.0 and 6.0 degrees C/s. 4. Magnitude estimates of pain for thirteen subjects also increased with rate of rise of temperature stimuli. Mean normalized magnitude estimates of heat pain were: 11.8 +/- 1.55, 15.1 +/- 0.84 and 28.0 +/- 1.87 for stimulus rates of rise of 0.3, 2.0 and 6.0 degrees C/s, respectively. 5. Results of simultaneous recordings of reaction time for pain and of C nociceptor responses to heat ramps given at 2.0 degrees C/s, in three subjects, indicate that under those circumstances heat pain messages are exclusively mediated by C nociceptors.

Characterization of variables defining hindpaw withdrawal latency evoked by radiant thermal stimuli

“…Although withdrawal latency decreased threefold from 9.1 to 3.2 s with increasing stimulus intensity, the tissue temperature at withdrawal was not different (41.5°C). These behavioral observations are in close accord with the thresholds for activation of C-fiber populations described above (Yarnitsky et al, 1992), and suggest that the reaction (paw withdrawal) mechanism was dependent upon tissue temperature but not rate of rise.…”

“…As will be considered below, it is assumed that the nociceptive response to the stimulus will reflect two components: the absolute temperature and the rate of rise. Single unit recording from slowly conducting afferent populations (C-fibers) in humans have shown a discharge threshold in the range of 41-42°C (Yarnitsky et al, 1992). At temperatures above this threshold, there is a rapid increase in the discharge frequency of these axons.…”

“…At temperatures above this threshold, there is a rapid increase in the discharge frequency of these axons. Moreover, for a given thermal stimulus, primary afferent discharge rates increase with increased rate of change (Beitel et al, 1977;Konietzny, 1984), and psychophysical studies in humans have also demonstrated that pain magnitude estimates and C-fiber primary afferent firing rates increase with increased rate of temperature change (Kenshalo et al, 1968;Yarnitsky et al, 1992).…”

Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: correlation with pain threshold in humans.

“…The correlation of pain sensation with CMH discharge rate extends into the suprathreshold range: both magnitude of heat pain and discharge rate of human CMHs were found to increase with increasing ramp rate (Yarnitsky, Simone, Dotson, Cline & Ochoa, 1992). We assumed that the contribution of type II A fibre mechano-heat-sensitive nociceptors (Meyer, Campbell & Raja, 1994) to pain threshold can be ignored because their median threshold in monkey hairy skin is 46°C (Treede, Meyer, Raja & Campbell, 1995).…”

Nociceptive sensations evoked from ‘spots’ in the skin by mild cooling and heating

“…Although the spots were detected at temperatures served by cold fibers and warm fibers, it has been assumed that sensations of burning, stinging or pricking arise from stimulation of nociceptors, which by definition have high thresholds and respond to noxious stimulation (Bessou and Perl 1969;Iggo and Ogawa 1971). The test temperatures of 28° and 36°C were specifically chosen to avoid stimulation of C-polymodal nociceptors (CPNs), which have average cold thresholds below 20°C (Simone and Kajander 1996;Campero et al 1996) and average heat thresholds above 40°C (Bessou and Perl 1969;Van Hees and Gybels 1981;Yarnitsky et al 1992). However, Georgopoulos (1976) reported a few Aδ-and C-mechano-thermal nociceptors in primates that were unusually sensitive to cold, with some having thresholds as high as 30°C.…”