Differential ability of human cutaneous nociceptors to signal mechanical pain and to produce vasodilatation.

We investigated the ability of human nociceptive primary afferent neurons to encode mechanical pain and to produce vasodilatation. Pain was induced by shooting a light metal cylinder (0.3 g) at different velocities (6-18 m/sec) perpendicularly against the hairy skin of the hand. When single impact stimuli were applied, monotonically increasing stimulus-response functions were obtained in 10 psychophysical experiments using magnitude estimation techniques. In 35 microneurographic experiments nine unmyelinated afferents were recorded from the superficial radial nerve. All units responded readily to impact stimulation even at stimulus intensities that were not rated as painful. However, there was a close linear correlation between the number of action potentials evoked from the nociceptors and the psychophysical magnitude estimates of the perceived sensation or the stimulus intensity. This was also reflected by a corresponding increase of neurogenic vasodilatation. While two thin myelinated afferents displayed qualitatively similar responses 12 low-threshold mechanosensitive afferents (4 rapidly adapting, 5 slowly adapting type 1, 3 slowly adapting type II) failed to encode the intensity of the applied impact force and often became desensitized. This indicates that the total number of action potentials is the determinant of the magnitude of mechanical pain and the associated vasodilatation following single brief stimuli. By contrast, the close correlation between nociceptor activity and sensation changed when trains of mechanical impact stimuli (five stimuli of constant intensity, intratrain frequency of 1/32 to 2 Hz) were applied. Magnitude estimates of pain intensity were frequency dependent and stimuli with short interstimulus intervals were perceived as more painful than those delivered with long intervals. However, the total number of action potentials evoked from C-fibers was higher at longer interstimulus intervals than shorter intervals, thus yielding a negative correlation between the magnitude estimates of the perceived painful sensation and the number of action potentials elicited from nociceptive afferents. This suggests that temporal summation of the nociceptive discharge at central neurons becomes increasingly more important for the sensory discriminative experience of pain evoked by repetitive stimulation. We conclude that human nociceptive C-fibers signal brief noxious mechanical stimuli by the total number of action potentials evoked during a short period of time. However, with repetitive stimulation the total number of action potentials evoked from nociceptors is less important for evoking pain and temporal summation of the nociceptive primary afferent discharge becomes the crucial factor for signaling the magnitude of sensation.