Is there a difference between heat-capsaicin induced low back pain and placebo for neural oscillations and inflammatory blood markers? An experimental randomized crossover study

Abstract

Purpose: Low back pain is difficult to study due to its heterogeneity. Inducing back pain experimentally, with an established model such as heat-capsaicin, would beneficially control for some variability. How heat-capsaicin affects neurophysiological factors relevant to back pain is currently unknown, therefore, this study used a randomized crossover design with the aim to explore the differences between heat-capsaicin and placebo on brain activity and blood markers.

Methods: 18 healthy participants completed two sessions: heat-capsaicin (45°C heat + capsaicin) and placebo (reduced heat + placebo). Pre- and post-pain-induction/placebo, electroencephalogram and blood draws were taken, and perceived pain was rated with a 100 m visual analog scale. Band power was calculated for theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), gamma1 (30-58 Hz), and gamma2 (62-100 Hz) for six brain regions. An immune assay was run on plasma in duplicate for cytokines IL-1β, IL-6, IL-10, and TNFα. A repeated measures ANCOVA was run for all variables comparing between conditions (heat-capsaicin, placebo) with baseline measures as covariates. A Pearson's correlation was used to determine the relationship between perceived pain ratings and brain wave and blood biomarkers.

Results: The heat-capsaicin model induced transient mild to moderate pain which was significantly higher than placebo (24.50 vs. 0.39; p < 0.001). Brain wave and blood biomarkers were not significantly different between heat-capsaicin and placebo (p ≥ 0.05) or correlated to perceived pain ratings (p ≥ 0.15).

Conclusion: Levels of perceived pain did not relate to neurophysiological changes that may occur immediately after heat-capsaicin exposure. Although changes have been found with other pain models and clinical low back pain, a statistically significant systematic response was not measurable using blood cytokine markers immediately after pain induction and may take longer to develop.

Keywords: EEG band power; brainwaves; cytokines; electroencephaloagraphy (EEG); experimental low back pain; heat-capsaicin; placebo.

Figure 1

Data collection protocol. *Informed consent was only collected prior to the first session.

Figure 2

Flow diagram demonstrating the randomized crossover design. Participants were pre-screened for inclusion/exclusion criteria prior to consenting and randomization.

Figure 3

Peak perceived pain ratings (100 mm VAS) were significantly different between the placebo and HC pain conditions (p < 0.001). Interpretation of pain scores is given along the x-axis.

Figure 4

Inflammatory blood markers were not significantly different between HC pain and placebo. Individual changes from pre- to post-condition were small and occurred in both directions. The diamonds and dashed black lines represent the averages for each blood marker, with green = placebo and red = HC pain.

Figure 5

Individual changes in the EEG frequency bands show that individual changes from pre- to post-condition were small and occurred in both directions. EEG frequency bands were not significantly different between HC pain and placebo. The diamonds and dashed black lines represent the averages for each blood marker, with green = placebo and red = HC pain.