Effects of nicotine compared to placebo gum on sensitivity to pain and mediating effects of peak alpha frequency

Abstract

Recent research has linked individual peak alpha frequency (PAF) to pain sensitivity, but whether PAF alterations can influence pain remains unclear. Our study investigated the effects of nicotine on pain sensitivity and whether pain changes are mediated by PAF changes. In a randomised, double-blind, placebo-controlled experiment, 62 healthy adults (18-44 years) received either 4 mg nicotine gum (n=29) or placebo (n=33). Resting state EEG and pain ratings during prolonged heat and pressure models were collected before and after nicotine intake. Nicotine reduced heat pain ratings and increased PAF speed across the scalp, driven by changes at central-parietal and right-frontal regions. However, mediation analysis did not support the notion that PAF changes mediate nicotine's effects on pain sensitivity. While a growing body of literature supports a link between PAF and both acute and chronic pain, further work is needed to understand the mechanisms of this link.

Peak alpha frequency is not significantly altered by five days of experimental pain and repetitive transcranial stimulation of the left dorsolateral prefrontal cortex

“…In our exploratory analysis, we found no significant correlations between baseline PAF and pain ratings at Day 5 for the entire sample or within individual groups, except for a significant positive correlation between baseline PAF and muscle soreness at Day 5 in the sham group. This positive correlation aligns with findings from some researchers (De Martino et al, 2021; Nir et al, 2010), while it contradicts findings from others (Furman et al, 2020, 2019, 2018; Millard et al, 2023). Additionally, linear mixed-effects models revealed significant interactions between pain intensity and group on PAF.…”

“…By examining which interventions produce concurrent effects and which do not, we may identify the specific aspects of the pain system that PAF reflects. Given the present results, alongside the existing literature (Millard et al, 2023; Sato et al, 2021), we could suggest that broad interventions like exercise and nicotine target aspects of pain processing associated with PAF, whereas those with a narrower spatial resolution, such as rTMS, may act on mechanisms independent of PAF (see Fernandes et al (2022) and Ciampi de Andrade and García- Larrea (2023) for recent reviews of mechanisms of rTMS for pain). Therefore, PAF likely reflects only a subset of the processes contributing to pain sensitivity, while other neurophysiological, cognitive, or psychological factors may also play significant roles.…”

“…Previous literature has demonstrated changes in PAF alongside changes in experimental pain using nicotine (Millard et al, 2023) and exercise alone, as well as exercise combined with tDCS (Sato et al, 2021), but not with tDCS alone (Sato et al, 2021) or rTMS in the present study. To understand how different interventions have selective influence on pain and/or PAF, we need to consider the complex and distributed nature of pain processing.…”

“…Few studies have assessed state changes in PAF related to pain in a controlled experimental setting (Millard et al, 2023; Sato et al, 2021), with most research assessing concurrent changes coming from the chronic pain literature (Heitmann et al, 2022; Ngernyam et al, 2015; Parker et al, 2021; Sarnthein et al, 2006; Sato et al, 2017; Sufianov et al, 2014). In this study, we conducted a secondary analysis to examine the effects of 10 Hz rTMS over the DLPFC on PAF alongside the known effects on experimentally induced NGF-pain (De Martino et al, 2019; Seminowicz et al, 2018), which is the first investigation using rTMS and experimental pain to investigate the PAF–pain relationship.…”

“…Additionally, this study only used one pain model (i.e. NGF), whereas incorporating multiple pain models could provide a more comprehensive understanding of the differential effects of interventions on different types of pain, as demonstrated in our other recent work on concurrent changes in PAF and pain (Millard et al, 2023) and recommended for the investigation of the PAF–pain relationship (Mazaheri et al, 2022).…”