Peripheral neural correlates of magnitude of cutaneous pain and hyperalgesia: simultaneous recordings in humans of sensory judgments of pain and evoked responses in nociceptors with C-fibers

Abstract

The peripheral neuronal correlates of heat pain elicited from normal skin and from skin made hyperalgesic following a mild heat injury were studied by simultaneously recording, in humans, evoked responses in C mechanoheat (CMH) nociceptors and the magnitude estimations of pain obtained from the same subjects. Subjects made continuous magnitude ratings of pain elicited by short-duration stimuli of 39-51 degrees C delivered to the hairy skin of the calf or foot before and at varying intervals of time after a heat injury induced by a conditioning stimulus (CS) of 50 degrees C, 100 s or 48 degrees C, 360 s. The stimuli were applied with a thermode pressed against the nociceptor's receptive field. For heat stimulations of normal skin, that is, uninjured skin, pain thresholds in 14 experiments with nine subjects ranged from 41 to 49 degrees C, whereas response thresholds for most of the 14 CMH nociceptors were 41 degrees C (in two cases, 43 degrees C). The latter suggested that spatial summation of input from many nociceptors was necessary at pain threshold. An intensity-response function was obtained for each CMH by relating the total number of nerve impulses evoked per stimulus to stimulus temperature. A corresponding magnitude scaling function for pain was obtained by relating the maximum rating of pain elicited by each stimulus to stimulus temperature. The relation between the subject's scaling function and the intensity-response function of his CMH nociceptor varied somewhat from one experiment to the next, regardless of whether the results were obtained from the same or from different subjects. However, when averages were computed for all 14 tests, there was a near linear relationship between the mean number of impulses elicited in the CMHs and the median ratings of pain, over the range of 45-51 degrees C. It was concluded that the magnitude of heat pain sensation was more closely related to the magnitude of response in a population of CMH nociceptors than in any individual nociceptor. At 0.5 min after the CS, the pain thresholds of most subjects were elevated, and the magnitude ratings of pain elicited by supra-threshold stimuli were lower than pre-CS values (hypoalgesia). Corresponding changes were seen in the increased thresholds and decreased responses (fatigue) of most CMHs. By 5-10 min after the CS, the pain thresholds of most subjects were lower, and their magnitude ratings of suprathreshold stimuli were greater than pre-CS values (hyperalgesia).(ABSTRACT TRUNCATED AT 400 WORDS)