Changes in pain from a repetitive thermal stimulus: the roles of adaptation and sensitization

Abstract

This study examined processes that contribute to the changing painfulness of a repeatedly presented thermal (heat) stimulus. The 3-second pulses were presented to the side of the hand at a rate of 4/min, too slow to engage wind-up. Over the course of 32 trials, pain intensity (measured by verbal report on a 0-100 scale) first declined and then (in most cases) rose again, indicating adaptation and sensitization, respectively. The magnitude of adaptation grew across a series of 3 runs, indicating that adaptation has a slow as well as a fast component. The rate of sensitization depended on stimulus temperature, but not on subjective pain intensity; this result implies that sensitization takes place at an early processing stage. Adaptation and sensitization were comparable in participants with fibromyalgia, temporomandibular disorders, and in healthy controls, indicating that these processes occur before the perceptual amplification that characterizes fibromyalgia and temporomandibular disorders. The ability of vibration to reduce pain has previously been shown to involve segmental inhibition; the finding in the present study that vibratory gating of pain is significantly (inversely) related to the rate of sensitization suggests that the latter also reflects segmental processes. Several lines of evidence thus point to the conclusion that adaptation and sensitization occur at early stages of sensory information processing.

Figure 1

Timeline of an experimental run. Each run consisted of 33 heat pulses, each 3 s in duration and separated by 12 s at a baseline temperature of 38°C. The subject rated the pain intensity of each pulse verbally using a 0–100 scale. Two temperatures varying by 0.5°C (selected for each subject individually on the basis of previous measurements) were pseudo-randomly interspersed, except for the third (probe) trial, in which a temperature 2°C lower than the low target temperature was used. The probe trial is not included in subsequent figures. Each subject participated in three runs: one with 33Hz vibration, one with 100Hz vibration, and one without vibration. The order of these runs was counterbalanced within each group. During runs with vibration present, the vibration started immediately after the subject rated the 12^th pulse of heat (not including the probe trial), and continued at a constant amplitude until the subject verbally reported the pain of the 22^nd pulse.

Figure 2

Time course of changes in responsiveness within a control (i.e., no-vibration) run consisting of 32 trials spaced at 15-s intervals. Each point is the pain intensity rating for one trial, averaged across all participants; error bars show ± 1 S.E.M. Stimulus temperature was adjusted for each subject to initially produce moderate pain. An initial drop in responsiveness was followed by a second phase during which pain increased for most subjects. The exponential curve drawn through the data of the first 8 trials represents the adaptation process. A regression line, representing slow temporal summation, has been fit to the data for trials 10–32. The two temperatures (differing by 0.5°C) employed for a given participant were pseudo-randomly ordered across trials, except that the lower of the two was always used on trial 1, and the higher on trial 2.

Fig. 3

Pain ratings for the three runs constituting the experimental session, averaged across all participants (FM, TMD, and HC). Breaks of 10 min separated consecutive runs. The order of the three types of runs (33Hz, 100Hz, and control) varied randomly across participants, subject to the constraint that each of the six possible orders occurred about equally often for members of each of the three clinical groups. The data shown here for each run (e.g. Run 1) are therefore averaged across runs of different types. Error bars represent ± 1 S.E.M.

Fig. 4

The rate of sensitization is plotted as a function of stimulus temperature. Rate is expressed in units of change (on the 0–100 pain intensity scale) per trial. Different symbols show the results for subjects with FM (squares), TMD (triangles), and for healthy controls (circles). Temperature for each subject is the mean of the two values used intermittently. Since regression slopes for the three groups were similar, a regression line fit to all the data is shown.

Fig. 5

The rate of sensitization is plotted as a function of pain intensity rating on the first trial of the series over which this rate was calculated. Different symbols show the results for subjects with FM (squares), TMD (triangles), and for healthy controls (circles).

Fig. 6

Pain intensity ratings over the course of control runs (circles), and runs in which 33Hz vibration was present during trials 13–22 (triangles). Data are averaged across all participants (FM, TMD, and HC). The order of the two types of runs was counterbalanced within each group. The area between the functions during and after the vibration period is shaded, to show the extent of vibratory pain modulation. Error bars represent ± 1 S.E.M.