Lateral inhibition during nociceptive processing

Abstract

Spatial summation of pain (SSP) is the increase of perceived intensity that occurs as the stimulated area increases. Spatial summation of pain is subadditive in that increasing the stimulus area produces a disproportionately small increase in the perceived intensity of pain. A possible explanation for subadditive summation may be that convergent excitatory information is modulated by lateral inhibition. To test the hypothesis that lateral inhibition may limit SSP, we delivered different patterns of noxious thermal stimuli to the abdomens of 15 subjects using a computer-controlled CO2 laser. Lines (5 mm wide) of variable lengths (4, 8 cm) were compared with 2-point stimuli delivered at the same position/separation as the length of lines. When compared with one-point control stimuli, 2-point stimulus patterns produced statistically significant SSP, while no such summation was detected during line stimulus patterns. Direct comparison of pain intensity evoked by 2-point pattern stimuli with line pattern stimuli revealed that 2-point patterns were perceived as significantly more painful, despite the fact that the 2-point pattern stimulated far smaller areas of skin. Thus, the stimulation of the skin region between the endpoints of the lines appears to produce inhibition. These findings indicate that lateral inhibition limits SSP and is an intrinsic component of nociceptive information processing. Disruption of such lateral inhibition may contribute substantially to the radiation of some types of chronic pain.

Conflict of interest statement

Conflict of Interest

The authors have no conflicts of interest.

Figures

Figure 1. Schematic illustration of the stimulus configuration (drawn to scale)

Two point and line stimuli were delivered at separation distances/lengths of 4, 8, and 12 cm. These stimuli were applied in a randomized order to the abdomen.

Figure 2. Stimulus temperatures (°C) for two-point vs. line stimuli (means±SEM)

Infrared video thermography revealed that stimulus temperatures were not different between 2 points and line patterns at 4cm and 8cm distances. However, at 12cm distances, the temperatures of the two-point stimuli were significantly lower than those of the lines. Accordingly, the 12cm psychophysical data have been excluded from analyses.

Figure 3. Pain intensity ratings by stimulus distance for two-point stimuli and lines (means±SEM)

Significant spatial summation was observed for two-point stimuli, but was not detected during the line stimuli (upper panels). The absence of detectable spatial summation during the line stimuli is notable due to the substantial increase in stimulus areas of the line stimuli as the lines grew longer (lower panels).

Figure 4. Pain intensity ratings for two-point vs. line stimuli (means±SEM. upper panel) and individual responses (lower panel)

Despite involving markedly larger stimulation areas than the two-point stimuli, the line stimuli were perceived as significantly less painful than two-point stimuli. This effect remained consistent over the two different stimulation distances. Inspection of individual ratings (lower panel) reveals some individual variation in this response, however, female subjects (grey circles) did not appear to exhibit responses that varied systematically from those of male subjects (black squares). Nevertheless, this discordance between stimulus area and perceived pain intensity indicates that the pattern of stimulus application represents a critical variable that shapes the balance of facilitory vs. inhibitory interactions between nociceptive inputs arising from multiple body regions. Thus, the greater pain experienced during the two-point vs. the line stimuli provides evidence for lateral inhibition during nociceptive processing.

Figure 5. Frequency of reports of different perceived spatial configurations

At 4 cm stimulation distances, the frequency of reports of different spatial configurations did not differ between 2 point stimuli and line stimuli. Both stimuli were characterized by frequent reports of “1 point” regardless of the stimulus type. However, at 8 cm distances subjects correctly reported “two points” most frequently during two-point stimuli, and “lines” most frequently during the line stimuli.