1. The responses of feline cutaneous nociceptors were examined in vivo by systematically manipulating the intensive and spatial dimensions of mechanical stimulation. A computer-controlled motor was used to apply prescribed forces (5-90 g) to a nociceptor's receptive field, with flat-tipped, cylindrical probes of various sizes (contact areas: 0.1-5.0 mm2). The stimulating device and protocols were similar to those previously used to evaluate human perception, thus allowing for comparisons of the two data sets. 2. With a ramp-and-hold stimulus of controlled force, most nociceptors showed a slowly adapting (SA) response throughout the stimulus. In this way, nociceptors resembled low-threshold SA mechanoreceptors. However, in contrast to SA mechanoreceptors, nociceptors failed to exhibit an onset burst of activity associated with the stimulus ramp. Nineteen percent (6 of 31) of the nociceptors often showed the opposite trend during the stimulus, e.g., a gradually increasing firing rate. Most of these nociceptors (5 of 6) had particularly high mechanical thresholds. 3. With 30 stimuli repeated at short intervals (6-8 s), response rates tended to decrease across trials. This phenomenon was most evident with more intense stimuli. When two series of stimuli were separated by 4-5 min, there was no apparent trend of reduced responsiveness between series. 4. Overall, nociceptors responded in an orderly way to variations in force and probe size. For a given probe size, larger forces produced greater responses; for a given force, smaller probes produced greater responses. The relationship between probe size and force was best described as an even tradeoff between force and a linear dimension of the probe (i.e., probe perimeter), rather than the area of the probe. Thus a given pressure (force/area) did not evoke the same response from nociceptors as probe size was varied. 5. There were two significant differences in the mechanical responsiveness between A fiber and C fiber nociceptors. First, for a given set of stimuli, A fiber nociceptors exhibited a greater response rate than the C fiber nociceptors. Second, the A fiber nociceptors exhibited a greater differential response related to probe size than the C fiber nociceptors. On the basis of these two features, the A fiber nociceptors' response profiles showed a closer parallel with previously reported human pain thresholds than the C fiber nociceptors did. 6. When the nociceptors were subdivided as to their mechanical threshold, those with lower thresholds [mechanically sensitive afferents (MSAs)] showed a response saturation with the more intense stimuli. On average, the stimulus levels at which saturation occurred were close to human pain threshold. Those nociceptors with higher thresholds [mechanically insensitive afferents (MIAs)] did not show such saturation. Thus only the MIAs appeared to have the capacity to unambiguously encode mechanical stimulus intensities above pain threshold. The MSAs, on the other hand, exhibited their greatest dynamic response range near the th...

Mechanical probes of various sizes and shapes were used to determine thresholds for the perception of pressure, sharpness, and pain on the human finger. As force increased, perception changed from dull pressure to sharp pressure to sharp pain. With the smallest probe (0.01 mm2), sharpness threshold was very close to pressure threshold. As probe size increased, sharpness and pain threshold expressed in terms of force) increased in proportion to probe circumference (not probe area), whereas pressure threshold increased relatively little. Pain and sharpness thresholds also increased as probe angle became obtuse. There was a statistically significant increase in both thresholds with a probe angle change of 15 degrees. Thus, both size and shape are necessary to describe a mechanical stimulus adequately, and pressure (force/area) is not a sufficient metric for pain studies. Thresholds varied at different skin sites on the finger. The dorsal surface had lower thresholds than the volar surface, but the difference between the two areas was not always statistically significant. The compliance of the skin (e.g., the amount of indentation produced by a given force) exhibited no relation to sharpness or pain threshold, whether considered within subjects at various skin sites, or across subjects at the same skin site. Comparison of the perceptual thresholds with the thresholds for nociceptors determined in electrophysiological studies indicates that the sensation of nonpainful sharpness is likely to be mediated by nociceptors. Furthermore, considerably more than threshold activation of nociceptors is necessary for normal pain perception.

Thirty-two healthy human subjects provided thresholds for the perception of slight and moderate heat pain. Four body sites were tested bilaterally: thenar eminence of the hand, plantar surface of the foot, dorsolateral forearm, and lateral calf. Thresholds for the glabrous skin of the hand and foot were significantly greater than thresholds for the hairy skin of the arm and leg, the average difference being 1.3 degree C. Laterality was not a statistically significant factor. Thresholds increased progressively over 2-4 weeks of repeated testing, resulting in values averaging 0.6 degree C higher in the later sessions. The difference between moderate and slight pain thresholds averaged 1.1 degree C, and was consistent across body sites and with repeated testing. The threshold values were normally distributed across subjects. Considerable intersubject variability was observed for both slight and moderate pain thresholds, more so on glabrous than on hairy skin sites. In comparison, the distribution of right-left difference values was narrower, demonstrating less intrasubject versus intersubject variability. The highly significant difference in thresholds between glabrous and hairy skin sites demonstrates the importance of skin type for heat pain sensitivity. In contrast, there was no significant difference in heat pain sensitivity between comparable sites on the upper versus lower extremities, or between left and right sides.

Psychophysically, spatial summation can be demonstrated as a decrease in threshold accompanying an increased field of stimulation. The present study examined to what extent different mechanically evoked percepts (pressure, sharpness, and pain) show spatial summation. Various probes were used to apply prescribed forces to the dorsal surface of the digits of 19 healthy subjects. The threshold for three perceptual qualities showed differing degrees of spatial summation: sharpness showed no statistically significant spatial summation; pain demonstrated some significant summation (46% on average); pressure showed the greatest degree of spatial summation (76% on average). The lack of significant spatial summation for sharpness threshold is consistent with the theory that perceived sharpness can be evoked by near threshold activity of a single nociceptor. The modest amount of spatial summation for pain implies that distinctly suprathreshold activation of nociceptors is required for mechanically evoked pain perception, and such input summates centrally, but not completely. The greater spatial summation observed for pressure vs. pain thresholds implies a greater degree of central summation for slowly adapting mechanoreceptors vs. nociceptors.

Twenty-four healthy human subjects provided thresholds for their perception of pressure, sharpness, and pain. Mechanical forces were applied to the dorsal surface of the digits with flat-tipped probes of various sizes. Thresholds (expressed as force) increased with increasing probe size, as previously described. There was no evidence of a laterality difference for any of the thresholds. There was a trend for increasing thresholds with repeated testing, but this trend was not statistically significant for the group as a whole. Examination of individual subjects' thresholds over time revealed that 27% showed significant increases in pain threshold over the 15 days of testing. In contrast, only 6% of subjects showed significant increases in sharpness or pressure thresholds over the same period. Thus, whereas most subjects exhibited stable pain thresholds, approximately one-fourth showed significant increases in pain threshold over time. We conclude that for evaluating regional dysesthesia or hemidysesthesia, a right-left difference in pain thresholds will provide a more sensitive and reliable measure than absolute pain threshold.