Sensitization of unmyelinated nociceptive afferents in monkey varies with skin type

1. Ninety-six C-fiber nociceptive afferents responsive to both mechanical and heat stimuli (CMHs) were studied in the monkey in an effort to determine what stimuli cause sensitization. Thirty-two of the fibers innervated glabrous skin (G-CMHs), while 64 innervated hairy skin (H-CMHs). Single-unit recording techniques were used. 2. The response to heat stimuli was studied with use of a laser thermal stimulator that provided stepped increases in skin temperature over a 7.5-mm-diameter area with rise times to the desired temperature near 100 ms for each stimulus. Changes in sensitivity were studied with a thermal test sequence (TTS), which consisted of 10 3-s stimuli presented with a 27-s interstimulus interval. The first stimulus was always 45°C. The remaining nine stimuli ranged from 41 to 49°C in 1°C increments and were presented in random order. The effects of stimulation with a more intense stimulus, 53°C for 30 s, were also determined. 3. The TTS stimuli were presented multiple times to the same fiber with a 10-min stimulus-free interval between runs. The H-CMHs were sensitized by the TTS stimuli, while the G-CMHs were not. Sensitization in the H-CMHs was manifest by a significant increase in the mean cumulative response to successive TTS stimuli, a significant decrease in thermal threshold, a significant increase in response to the first stimulus of each TTS run (viz., 45°C), and the development of spontaneous activity in certain of the H-CMHs. These changes in responsiveness were not observed in the G-CMHs. 4. Presentation of more intense stimuli (53°C for 30 s) caused further sensitization in many of the H-CMHs, but the effect was not significantly different from the change evoked by presentation of the TTS stimuli. The G-CMHs did not sensitize to the 53°C, 30-s stimulus (burn), and in most fibers suppression occurred, as measured by the response to the TTS stimuli 10 min after the burn. The suppression tended to be less marked 25 min after the burn. 5. The difference between H-CMHs and G-CMHs cannot be explained by a difference in the initial sensitivity of the two types of fibers. The mean responses to the initial 45°C stimulus of the first TTS run were similar: 10.3 ± 1.3 (SE) impulses for G-CMHs, and 9.8 ± 1.8 impulses for H-CMHs. The thermal thresholds, as measured by the response to the first TTS run, were also similar: 44.3 ± 0.3°C for G-CMHs, and 44.6 ± 0.2°C for H-CMHs. 6. The increased response to the TTS stimuli over successive runs for the H-CMHs tended to reach a plateau by the fourth run. The additional application of the burn in a few of these fibers failed to increase the response to TTS stimuli further. 7. In 10 H-CMHs, the duration of the TTS stimuli was changed from 3 to 1 s and runs were repeated after 10-min stimulus-free intervals. In contrast to the increased response evoked by 3-s stimuli, the mean response of the H-CMHs to the 1-s stimuli did not change significantly over successive runs. 8. Alhough the H-CMHs showed sensitization from one run to the next, within a run only suppression was evident. For example, the response to the second 45°C stimulus of the TTS in the first run was 31 ± 5% of the response evoked by the first 45°C stimulus within the same run. 9. The conduction velocity and receptive-field size of the H-CMHs and G-CMHs did not differ. However, the mechanical threshold of the H-CMHs (2.51 ± 0.11 bars) was significantly less than that of the G-CMHs (4.27 ± 0.32 bars, P<0.001). 10. It is concluded that H-CMHs and G-CMHs differ significantly with regard to the propensity to sensitize to noxious heat stimuli. H-CMHs sensitize readily, and G-CMHs given the same stimuli do not sensitize. These results suggest that C-fiber nociceptive afferents do not play an important role in hyperalgesia in glabrous skin but may play an important role in hyperalgesia in hairy skin. This finding also supports the hypothesis that A-fiber nociceptive afferents play an important role in explaining the marked hyperalgesia that is produced by a substantial thermal injury (52°C for 30 s) to the glabrous skin of the hand.