Nonlinear increase of pain in distance-based and area-based spatial summation

Abstract

When nociceptive stimulation affects a larger body area, pain increases. This effect is called spatial summation of pain (SSp). The aim of this study was to describe SSp as a function of the size or distance of a stimulated area(s) and to test how this function is shaped by the intensity and SSp test paradigm. Thirty-one healthy volunteers participated in a within-subject experiment. Participants were exposed to area-based and distanced-based SSp. For area-based SSp, electrocutaneous noxious stimuli were applied by up to 5 electrodes (5 areas) forming a line-like pattern; for distance-based SSp, the same position and lengths of stimuli were used but only 2 electrodes were stimulated. Each paradigm was repeated using pain of low, moderate, and high intensity. It was found that the pattern of pain intensity followed a logarithmic (power) rather than a linear function. The dynamics of the pain increase were significantly different across pain intensities, with more summation occurring when pain was perceived as low. Results indicated that area-based SSp is more painful than distance-based SSp when low and moderate but not when high pain intensity is induced. Presented findings have important implications for all studies in which the spatial dimension of pain is measured. When the area or separation between nociceptive stimulation increases, pain does not increase linearly and the pattern of the pain increase is a result of the interaction between intensity and the number of nociceptive sites. A power function should be considered when predicting the size of a nociceptive source.

To Calibrate or not to Calibrate? A Methodological Dilemma in Experimental Pain Research

“…Thus, not only variability relates to peripheral input, but also pain ratings per se. This can be confirmed by our own data (see Figure 1) and all other reports with individual approaches [1,22,67]. Furthermore, calibration is not 100% precise.…”

“…Alternatively, it seems logical to implement a variety of stimulus ranges applied in the fixed manner to obtained both types of data: calibrated and fixed. In fact, many studies followed such a design [1,50,74]. For example, in a study by Weissman-Fogel et al [74], participants received tonic noxious heat stimulation calibrated to induce pain of 2, 4 and 6 out of 10.…”

“…Unlikely to be affected by ceiling and/or floor effects [21,42] Prone to floor/ceiling effects [2,22,42] Neural activity Differential intensity encoding at the spinal cord and thalamus level [61] Equal activation patterns until thalamus level [9,61] Feasibility Time-consuming technique [1,51] Time-saving technique [6] Translation Humans less comparable to studies on other species Studies in humans comparable to studies with animal models Sensitization Depending on the calibration protocol, potential to irritate the pain system [63] Lack of pre-exposure in the experiment setup [65] Study design More desirable in studies targeted at subjective outcomes (e.g., pain ratings) [42] More desirable in studies targeted at with physiological outcomes (e.g., fMRI) [42] Peripheral factors…”

Spatial tuning in nociceptive processing is driven by attention

“…The LMM analysis with skin temperature as a covariate lead to similar results as the original ANOVA. In brief, main effect of “trial”, remained statistically significant ( F [6,520] = 9.42, p < 0.001, η 2 p = 0.10), and neither factor “block” ( F [1,520] = 1.08, p = 0.30, η 2 p = 0.03) nor “trial” × “block” interaction ( F [6,520] = 0.43, p = 0.86, η 2 p = 0.01) was significant. Contrasts corrected by skin temperature are reported in Appendix 3 .…”

“…Spatial tuning can be broad and allow information to be collected from widespread body regions, or spatial tuning could be narrow to optimize extraction of information from very focal areas. The relatively broad spatial tuning can be responsible for enhanced SSp, whereas focused tuning might effectively hamper SSp such that pain summation is reduced 15 , disproportionate 23 , nonlinear 1 , or in some circumstances, is even absent 1,39 . At a mechanistic level, tuning may be accomplished by a complex interaction between facilitatory and inhibitory processes that regulate receptive field (RF) sizes of nociceptive neurons within the central nervous system 4,8,37 leading to a determination of spatial attributes of perceived pain.…”