Characteristics of Temporal Summation of Second Pain Sensations Elicited by Brief Contact of Glabrous Skin by a Preheated Thermode

Abstract

Temporal summation of sensory intensity was investigated in normal subjects using novel methods of thermal stimulation. A Peltier thermode was heated and then applied in a series of brief (700 ms) contacts to different sites on the glabrous skin of either hand. Repetitive contacts on the thenar or hypothenar eminence, at interstimulus intervals (ISIs) of 3 s, progressively increased the perceived intensity of a thermal sensation that followed each contact at an onset latency > 2 s. Temporal summation of these delayed (late) sensations was proportional to thermode temperature over a range of 45-53 degrees C, progressing from a nonpainful level (warmth) to painful sensations that could be rated as very strong after 10 contacts. Short-latency pain sensations rarely were evoked by such stimuli and never attained levels substantially above pain threshold for the sequences and temperatures presented. Temporal summation produced by brief contacts was greater in rate and amount than increases in sensory intensity resulting from repetitive ramping to the same temperature by a thermode in constant contact with the skin. Variation of the interval between contacts revealed a dependence of sensory intensity on interstimulus interval that is similar to physiological demonstrations of windup, where increasing frequencies of spike train activity are evoked from spinal neurons by repetitive activation of unmyelinated nociceptors. However, substantial summation at repetition rates of > or = 0.33 Hz was observed for temperatures that produced only late sensations of warmth when presented at frequencies < 0.16 Hz. Measurements of subepidermal skin temperature from anesthetized monkeys revealed different time courses for storage and dissipation of heat by the skin than for temporal summation and decay of sensory intensity for the human subjects. For example, negligible heat loss occurred during a 6-s interval between two trials of 10 contacts at 0.33 Hz, but ratings of sensory magnitude decreased from very strong levels of pain to sensations of warmth during the same interval. Evidence that temporal summation of sensory intensity during series of brief contacts relies on central integration, rather than a sensitization of peripheral receptors, was obtained using two approaches. In the first, a moderate degree of temporal summation was observed during alternating stimulation of adjacent but nonoverlapping skin sites at 0.33 Hz. Second, temporal summation was significantly attenuated by prior administration of dextromethorphan, a N-methyl-D-aspartate receptor antagonist.

Brain activity related to temporal summation of C-fiber evoked pain

“…Because glabrous foot areas are most distant from the spinal cord and brain, delayed pain sensations (2 nd pain) are well separated from early sensations such as 1 st pain and can be easily detected by study subjects. Although heat pulses applied to the glabrous skin of the foot can evoke brief latency sensations of weak pain or warmth, they do so only during the first two pulses of a heat pulse train (Price et al, 1977;Price et al, 1994;Vierck et al, 1997). Thus, pain ratings and measures of neural activity in proximity to the last pulse of a six pulse stimulus train (as used in our study) almost exclusively result from C-fiber input and TSSP.…”

“…Pain-A standardized numerical pain scale (NPS) was utilized for rating the magnitude of painful sensations produced by thermal stimulation as described previously (Vierck et al, 1997;Staud et al, 2006). The scale ranged from 0 to 100, in increments of 5, with verbal descriptors at intervals of 10: 0 = no sensation, 10 = warm, 20 = a barely painful sensation (i.e.…”

“…pain threshold), 30 = very weak pain, 40 = weak pain, 50 = moderate pain, 60 = slightly strong pain, 70 = strong pain, 80 = very strong pain, 90 = nearly intolerable pain, and 100 = intolerable pain. Previous experience with the scale has shown that increments of 5 provide appropriate resolution for discriminable levels of late sensation intensity from threshold to nearly intolerable levels (Vierck et al, 1997;Staud et al, 2001). This numerical scale has been found to be particularly advantageous for pain ratings during series of repetitive stimuli (Vierck et al, 1997).…”

“…Although the subjects were required to be pain free at enrollment somatic pain ratings were obtained before and during the scanning session to capture possible new onset pains like back pain, headache, etc. The scales were anchored on the left with "no pain/anxiety at all" and on the right with "the most intense pain/anxiety imaginable" (Vierck et al, 1997). Ratings of somatic pain and anxiety were obtained before and after each scanning run.…”

“…A brief nociceptive stimulus, like a heat tap or electrical stimulation of A and C axons, can evoke two distinct pain sensations called, 'first' and 'second' pain (Price, 1972;Price et al, 1977;Vierck et al, 1997). First pain is an immediate sensation, whereas second pain occurs up to two seconds later and can be a dull, throbbing, or burning sensation.…”