Mean ± standard deviations (SD) for baseline participant characteristics split by gum group.

Mean ± standard deviations (SD) for pain ratings during phasic heat pain (PHP) and cuff pressure algometry (CPA), for pre- and post-gum, for the whole sample and separated by nicotine and placebo groups.

Percentage of participants reporting each category descriptor of pain on the McGill pain questionnaire for A) phasic heat pain (PHP) and B) cuff pressure algometry (CPA) at baseline. Average pain time courses split into nicotine (orange, n = 29) and placebo (grey, n = 33) gum groups for C) PHP and D) CPA models of prolonged pain. Raincloud plots of mean pain ratings during E) PHP and F) CPA models of prolonged pain.

A) Individual spectral plots of eyes closed (EC) resting state EEG data showing dominant peaks within the alpha range of 8–12 Hz. Note that many participants’ peaks fall outside the narrow 9–11 Hz window. Top panel shows individual spectra for participants in the placebo group (in grey, n = 33), bottom panel shows individual spectra for participants in the nicotine group (in orange, n = 29). B) Spectral plots of eyes closed (EC) resting state EEG shows averaged spectra by group and time point. C) Raincloud plots of mean global and D) sensorimotor PAF values, calculated with a wide window (8–12 Hz) and the centre of gravity method, before and after chewing either nicotine (in orange) or placebo (in grey) gum. E) Topographical plots of PAF calculated for each electrode with the centre of gravity method and 8–12 Hz window are shown for the pre-gum baseline (rest 1) and post-gum (rest 3). F) Topographical plot of t-test statistics produced by cluster-based permutation analysis of nicotine group, displaying significant difference in PAF after chewing nicotine gum in two separate clusters marked by crosses (x).

Path model displaying unstandardised estimates and p-values for the difference score two-wave latent change score (2W-LCS) model assessing the effect of nicotine against placebo (i.e. gum group) on change in global 8–12 Hz peak alpha frequency (i.e. ΔPAF) and change in mean phasic heat pain (PHP) ratings (i.e. ΔPain). Green arrows highlight the indirect effects (i.e. a and b), the red arrow highlights the direct effect (i.e. c’), the blue lines highlight pre-determined confounding variables, and dashed lines denote fixed effects. This model suggests that chewing nicotine gum, compared to placebo, increases the speed of PAF, and decreases PHP ratings, however the change in PAF does not influence the change in PHP ratings, therefore changes in PHP ratings after nicotine gum are not mediated by changes in PAF.

Mean ± standard deviations (SD) for sensorimotor and global peak alpha frequency (PAF) pre- and post-gum chewing, for the whole sample and by nicotine and placebo groups. PAF calculated for wide frequency window (8–12 Hz) with the centre of gravity method.

Path model displaying unstandardised estimates and p-values for the difference score two-wave latent change score (2W-LCS) model assessing the effect of nicotine against placebo (i.e. gum group) on change in global 8–12 Hz peak alpha frequency (i.e. ΔPAF) and change in mean cuff pressure algometry (CPA) ratings (i.e. ΔPain). Green arrows highlight the indirect effects (i.e. a and b), the red arrow highlights the direct effect (i.e. c’), the blue lines highlight pre-determined confounding variables, and dashed lines denote fixed effects. This model suggests that chewing nicotine gum, compared to placebo, increases the speed of PAF and does not influence CPA ratings, directly or indirectly.

Wide band (8–12 Hz) global peak alpha frequency (PAF) does not correlate with A) mean pain ratings during phasic heat pain (PHP) or B) cuff pressure algometry (CPA). Regression lines and shaded 95% confidence intervals. Correlations separated by sex for females in teal (n = 32) and males in brown (n = 30) for C) PHP and D) CPA, suggest a strengthening of a negative relationship between sensorimotor PAF and PHP ratings for males (BF10 = 3.22).

Timeline of experimental events. Electroencephalography (EEG) data were collected during eyes open and eyes closed resting states before and after each pain assessment. Prolonged pain assessments consisted of cuff pressure algometry (CPA) followed by phasic heat pain (PHP) models, and took place before and after gum chewing.

Overview of mediation models.

Adapted from Valente and MacKinnon [62]. The analysis of covariance (ANCOVA) equivalent pre-test/post-test control group design (two-wave) with latent change score (LCS) specification for the outcome (Y: pain) and mediating (M: PAF) variables. The direct effect of the intervention on the outcome is represented by the red line (c’y2x). The intervention–mediator relationship is represented by a green line (am2x) from the intervention (i.e. X: nicotine vs. placebo) to the mediator (i.e. ΔM). The mediator–outcome relationship is represented by another green line (by2m2) from the mediator (i.e. ΔM) to the outcome (i.e ΔY). Together the two green lines represent the indirect effect of the intervention on the outcome via the mediator. Time-lagged autoregression paths are represented by S∗m2m1 and S∗y2y1. Cross-lagged coupling paths are represented by bm2y1 and b∗y2m1. The covariance between Y and M at baseline is represented by σm1y1. The potential confounders of the mediator–outcome relationship were measured at baseline and are represented by the blue dashed lines. Note. ∗ = latent; X = intervention (i.e. gum); M = mediator (i.e. PAF); Y = outcome (i.e. pain).

Adapted from Valante and MacKinnon [62]. The difference score model with latent change score specification for the outcome (Y) and mediating (M) variables. The direct effect of the intervention on the outcome is represented by the red line (c’Δ). The intervention–mediator relationship is represented by a green line (am2x) from the intervention (i.e. X: nicotine vs. placebo) to the mediator (i.e. ΔM). The mediator–outcome relationship is represented by another green line (bΔ) from the mediator (i.e. ΔM) to the outcome (i.e ΔY). Together the two green lines represent the indirect effect of the intervention on the outcome via the mediator. Cross-lagged coupling paths are constrained to 0 and time-lagged autoregressions are constrained to 1. The covariance between Y and M at baseline is represented by σm1y1. The potential confounders of the mediator–outcome relationship are represented by the blue dashed lines. Note. X = intervention (i.e. gum); M = mediator (i.e. PAF); Y = outcome (i.e. pain).