Strong and aversive cold processing and pain facilitation in fibromyalgia patients relates to augmented thermal grill illusion

Abstract

The thermal grill illusion (TGI) is assumed to result from crosstalk between the thermoreceptive and nociceptive pathways. To elucidate this further, we compared 40 female fibromyalgia patients to 20 healthy women in an exploratory cross-sectional study. Sensations (cold, warm/heat, unpleasantness, pain and burning) evoked by 20 °C, 40 °C and alternating 20 °C/40 °C (TGI) and somatosensory profiles according to standardized quantitative sensory testing (QST) were assessed on the palm of the dominant hand. Compared to healthy controls, fibromyalgia patients reported stronger thermal grill-evoked cold, warm, unpleasantness and pain as well as stronger and more aversive 20 °C- and 40 °C-evoked sensations. They showed a loss in warm, mechanical and vibration detection, a gain in thermal pain thresholds and higher temporal summation (TS). Among QST parameters higher TS in fibromyalgia patients was most consistently associated with an augmented TGI. Independently, an increased TGI was linked to cold (20 °C) but less to warm (40 °C) perception. In fibromyalgia patients all thermal grill-evoked sensations were positively related to a higher 20 °C-evoked cold sensation and/or 20 °C-evoked unpleasantness. In conclusion, the TGI appears to be driven mainly by the cold-input. Aversive cold processing and central pain facilitation in fibromyalgia patients seem to independently augment the activation of the pain pathway.

Figure 1

Study flow chart.

Figure 2

QST profile of Fibromyalgia patients. Z-Scores of sensory thresholds of fibromyalgia patients (n = 40) calculated with reference to the healthy control group (n = 20) with z = (x–mean(healthy))/SD(healthy); CDT Cold detection threshold; WDT Warm detection threshold; TSL Thermal sensory limen; CPT Cold pain threshold; HPT Heat pain threshold; MDT Mechanical detection threshold; MPT Mechanical pain threshold; MPS Mechanical pain sensitivity; WUR Wind-up ratio; VDT_Lim Vibration detection threshold by the method of limits (x/8); VDT_Lev Vibration detection threshold by the method of levels in microns; PPT Pressure pain threshold; *significant difference in comparison to the healthy control group on an α-level of 5%.

Figure 3

Sensations during contact with the cold and warm plate and under the thermal grill condition. (a, b, c, d) Box plots indicating median and interquartile range (IQR) as well as outliers (> 1.5 IQR) of the intensity of cold and warm/heat sensations, unpleasantness and pain on a numeric rating scale (NRS 0–100); statistical comparisons within groups by Wilcoxon rank-sum test and between groups by Mann–Whitney-U test; (e) Proportion of patients with a burning sensation—statistical comparison within groups by McNemar test and between groups by Fisher test; cold plate (20 °C): white boxes/bars, warm plate (40 °C): dotted boxes/bars, thermal grill condition (20 °C/40 °C): striped pattern boxes/bars; healthy: white shaded boxes/bars; fibromyalgia patients: grey shaded boxes/bars; *significant between group difference on an α-level of 5%; # significant within group difference on an α-level of 5%; p-values for group comparisons are displayed in Table2.

Figure 4

Associations of thermal grill (20 °C/40 °C)-evoked sensations with the temporal summation and cold (20 °C)-evoked sensations. Y-axes represent the thermal grill-evoked sensations and x-axes the log-transformed wind-up ratio (WUR_log quantifying temporal summation of pain, TS) and 20 °C-evoked sensations respectively. Scatter plots illustrate associations between continuous variables. Here, cases with 20 °C- and/or 40 °C-evoked pain are depicted as crosses and the remaining cases as points. Box-plots illustrate associations between a continuous and a dichotomous variable and bar plots associations between two dichotomous variables. Associations were evaluated by generalized linear models (GLM) or by the Fisher test in case of mutual exclusive categories of the dependent and independent variable without adjustment. Regression coefficients with respective confidence intervals are listed in Supplementary Table S2; *significant on an α-level of 5%; NRS Numeric rating scale.