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)

Relationships Between Skin Temperature and Temporal Summation of Heat and Cold Pain

“…Psychophysical thresholds for heat pain range from 40 to 49 for stimulation at glabrous and hairy skin sites with probes of different sizes and with widely varying ramp rates and stimulus durations (Hamalainen et al 1982;LaMotte 1984;LaMotte et al 1983;Morin and Bushnell 1998;Pertovaara et al 1996;Strigo et al 2000;Wahren et al 1989;Yarnitsky and Ochoa 1991). Most of the mean threshold values cluster between 43 and 46°C (Craig and Bushnell 1994;Dyck et al 1993;Hardy et al 1952;Harju 2002;Magerl and Treede 1996;Nielsen and Arendt-Nielsen 1998;Taylor et al 1993;Tillman et al 1995;Torebjork et al 1984;Verdugo and Ochoa 1992). In experiment 2 of this study, eVAS ratings of 10 represent a conservative estimate of threshold pain.…”

“…The lowest threshold reported for activation of C nociceptors is approximately 40°C (LaMotte and Thalhammer 1982;LaMotte et al 1983;Torebjork et al 1984;Yarnitsky et al 1992) and is well below thresholds as high as 53°C for activation of A-delta thermal nociceptors in glabrous skin (LaMotte and Campbell 1978;LaMotte et al 1983;. Psychophysical thresholds for heat pain range from 40 to 49 for stimulation at glabrous and hairy skin sites with probes of different sizes and with widely varying ramp rates and stimulus durations (Hamalainen et al 1982;LaMotte 1984;LaMotte et al 1983;Morin and Bushnell 1998;Pertovaara et al 1996;Strigo et al 2000;Wahren et al 1989;Yarnitsky and Ochoa 1991).…”

An inhibitory interaction of human cortical responses to stimuli preferentially exciting Aδ or C fibers

“…The lack of perceived intensity difference may be because the brevity of each stimulus did not provide the temporal summation necessary for accurate intensity estimation (Torebjork et al, 1984;Magerl et al, 1999); in addition, the short intervals between the CS and TS may have impaired the ability of our subjects to discriminate clearly between them and to evaluate intensity differences easily. Finally, the evoked potentials we recorded at Cz are probably generated within or near the anterior cingulate gyrus (Lenz et al, 1998) and their amplitudes may not be specifically and exclusively related to perceived stimulus intensity.…”

Two Types of C Nociceptors in Human Skin and Their Behavior in Areas of Capsaicin-Induced Secondary Hyperalgesia

“…The primary hyperalgesia at the site of capsaicin application features increased sensory responses to both mechanical and heat stimuli, attributed to sensitization of cutaneous nociceptor terminals, both of the common polymodal type (Campbell and Meyer 1983;LaMotte et al 1982LaMotte et al , 1983LaMotte et al , 1992Torebjörk et al 1984) and of the more recently described mechano-insensitive type of C nociceptor (Davis et al 1993;Meyer et al 1991;Schmelz et al 2000b;Schmidt et al 1995). The neural mechanisms underlying the secondary hyperalgesia in surrounding skin remain unclear.…”