Autonomic Indices of Negative Emotion Regulation Predict Treatment Response in Opioid-Treated Chronic Low Back Pain

Abstract

Difficulties engaging in emotion regulation strategies, such as cognitive reappraisal, may contribute to heightened pain severity, functional interference and poorer treatment response among adults with chronic low back pain (CLBP) receiving long-term opioid therapy (LTOT). This study used high-frequency heart rate variability (HF-HRV) as a physiological index of negative emotion regulation capacity to examine its influence on psychological treatment outcomes in opioid-treated CLBP. Participants (N = 68) were adults with opioid-treated CLBP enrolled in the Salt Lake City site of a multisite randomized clinical trial comparing mindfulness-based therapy (MBT) and cognitive behavioral therapy (CBT) adjunctive to usual care. At baseline, participants completed an emotion regulation task involving passive viewing and cognitive reappraisal of negative affective stimuli while HF-HRV was recorded. They also completed the Brief Pain Inventory (BPI) to assess pain severity and functional interference. Participants were then randomized to 8 weeks of MBT (n = 41) or CBT (n = 27) and completed BPI assessments at 3-, 6-, 9-, and 12-month follow-ups. Linear mixed-effects models revealed that lower baseline reappraisal capacity, as indicated by blunted phasic HF-HRV during the emotional regulation task, significantly predicted higher pain severity and interference following treatment with MBT or CBT through 12-month follow-up. Findings suggest that attenuated ability to regulate autonomic responses during reappraisal of negative emotional stimuli may contribute to more refractory pain outcomes as long as a year later among individuals engaged in evidence-based psychological treatments. Enhancing emotion regulation strategies, like cognitive reappraisal, may strengthen autonomic functioning and improve pain-related outcomes.

Introduction

Approximately one in five adults in the United States experiences chronic pain,¹ a biopsychosocial phenomenon associated with elevated psychological distress^2–4 and increased risk of psychiatric disorders such as depression and anxiety.⁵ These emotional challenges are reciprocally related to and can significantly impact pain treatment response.⁶ Pain frequently elicits negative emotions, especially when perceived as chronic, threatening, or uncontrollable.^7–10 In turn, negative emotions can amplify pain severity and activate neural regions involved in its sensory and affective regulation.^11–14 Prolonged activation of this overlapping circuitry increases pain hypervigilance and heightens its severity and unpleasantness, fueling a cycle of physical and emotional suffering.^15–17

To disrupt this cycle, strategies that promote emotion regulation (ER) are needed.¹⁸ One such strategy is cognitive reappraisal—the process of reframing the meaning of an adverse event to mitigate its negative emotional impact.¹⁹ Reappraisal been shown to reduce negative affect, dampen physiological reactivity to emotional stimuli,^19–21 and decrease pain severity.^22–26 However, individuals with chronic pain often struggle to employ ER strategies like reappraisal,^27,28 which may exacerbate pain severity and functional impairment^18,24,29 and increase reliance on maladaptive coping strategies, including opioid misuse.^30,31

Given these links, interventions targeting ER may be particularly effective for chronic pain management. Reappraisal is a core ER strategy in cognitive-behavioral therapy (CBT), the current “gold standard” for chronic pain.³² Mindfulness-based therapy (MBT), which emphasizes pain acceptance and reducing emotional reactivity,³³ has also been shown to improve ER and pain coping.^34,35 Although reappraisal is not an explicit focus of most MBT, theory and evidence suggests that mindfulness training can strengthen reappraisal capacity,^36,37 even without direct instruction.^38,39

Although CBT and MBT are well-supported interventions for chronic pain,^40–43 it remains unclear how specific ER strategies like reappraisal contribute to their efficacy.^44–46 Further, most studies examining ER in chronic pain populations rely on self-report measures, which are vulnerable to biases and may insufficiently capture ER processes as they occur in real-world contexts.^47–49 Consequently, psychophysiological measures, such as heart rate variability (HRV), are increasingly used to assess ER.⁵⁰

Regulating responses to emotionally salient stimuli is thought to engage a central autonomic network modulating attention, emotion, and physiological functions. One important output of this network is high-frequency HRV (HF-HRV; 0.15–0.40 Hz), the parasympathetically mediated variation in time intervals between consecutive heartbeats.^51–54 HF-HRV is considered a broad, homeostatic index of autonomic flexibility supporting cardiovascular, pain, and emotional regulatory processes.^51–54 Higher HF-HRV is thought to reflect greater prefrontal modulation of subcortical circuitry involved in self-regulation, including downregulation of negative emotions.^55–57 Among healthy individuals, higher resting HF-HRV is associated with fewer self-reported ER difficulties and more effective coping with daily stressors.^55,56,58 Following stressful cue exposure, phasic increases in HF-HRV are viewed as indexing the capacity to modulate autonomic responses during emotional provocation, with such increases frequently observed during reappraisal efforts.^58–60

In chronic pain populations, HF-HRV measured during a validated ER task has served as a physiological marker of reappraisal capacity, with attenuated HF-HRV during reappraisal attempts linked to adverse outcomes such as opioid misuse.⁶¹ However, no studies have examined whether HF-HRV reappraisal indices predict pain-related treatment outcomes. Therefore, this exploratory analysis tested whether cognitive reappraisal capacity, indexed via HF-HRV during this same validated ER task, predicted pain severity and functional interference in a subset of participants enrolled in a multisite randomized clinical trial (RCT) comparing MBT and CBT in adults with opioid-treated chronic low back pain (CLBP).⁶² In this trial, both treatments significantly and comparably decreased pain severity and functional interference through 12-month follow-up.⁶³ The current analysis examined baseline HF-HRV to understand individual differences in treatment response, hypothesizing that lower HF-HRV would be associated with smaller reductions in pain severity and interference over time.

Methods

Participants

This secondary analysis examined data from a subset of participants enrolled in a multisite RCT (NCT03115359) comparing MBT to CBT among adults with opioid-treated CLBP.⁶² Participants were included in the present analysis if they had complete HF-HRV data from an ER task administered at baseline. Because COVID-19-related disruptions limited physiological data collection, only a limited subset of participants enrolled in the Salt Lake City site completed the ER task, resulting in a final sample of 68 individuals (see Table 1).

Table 1.

Demographic and clinical characteristics of the sample of opioid-treated patients with chronic low back pain

	Total (N = 68)	MBI (n = 41)	CBT (n = 27)
Age	58.3 ± 10.9	57.4 ± 10.8	59.6 ± 11.2
Female, N (%)	41 (60.3%)	24 (58.5%)	17 (63.0%)
Racial/ethnic background, N (%)a
White	61 (89.7%)	37 (90.2%)	24 (88.9%)
Hispanic or Latino	5 (7.4%)	3 (7.3%)	2 (7.4%)
American Indian/Alaska Native	2 (2.9%)	1 (2.4%)	1 (3.7%)
Asian	1 (1.5%)	0 (0.0%)	1 (3.7%
Black	1 (1.5%)	0 (0.0%)	1 (3.7%)
Other or Unknownb	4 (5.9%)	3 (7.3%)	1 (3.7%)
Highest Level of Education, N (%)
High school/G.E.D. or below	12 (17.6%)	9 (22.0%)	3 (11.1%)
Some college	20 (29.4%)	13 (31.7%)	7 (25.9%)
Occupational/technical/vocational program	9 (13.2%)	4 (9.8%)	5 (18.5%)
Associate’s degree	9 (13.2%)	6 (14.6%)	3 (11.1%)
College degree or greater	18 (26.5%)	9 (22.0%)	9 (33.3%)
Estimated household income, N (%)
Less than $25,000	25 (36.8%)	17 (41.5%)	8 (29.6%)
$25,000–49,999	16 (23.5%)	11 (26.8%)	5 (18.5%)
$50,000–99,999	15 (22.1%)	8 (19.5%)	7 (25.9%)
$100,000 or greater	8 (11.8%)	4 (9.8%)	4 (14.8%)
Not reported	4 (5.9%)	1 (2.4%)	3 (11.1%)
Average pain severity (0–10), BPI	6.1 ± 1.3	6.0 ± 1.4	6.2 ± 1.3
Pain interference (0–10), BPI	7.3 ± 1.5	7.6 ± 1.5	6.7 ± 1.5
Morphine Equivalent Daily Dose, in mg, med (IQR)	60.0 (88.1)	45 (82.5)	67.5 (77.5)

Note. BPI = Brief Pain Inventory

^aBecause participants could report multiple racial/ethnic identities, percentages could sum to greater than 100%.

The parent clinical trial had both a stakeholder advisory committee and a patient family advisory committee. These committees were involved in the study’s conceptualization, design, choice of outcome measures, recruitment, and dissemination of the study results.

Participants were recruited from community settings, and primary care pain medicine clinics. Eligibility was determined through self-report and included being fluent in English, aged 21 years or older, having CLBP with an average daily pain intensity score of > 3 on a 0–10 numerical rating scale from the Brief Pain Inventory;⁶⁴ experiencing moderate or greater CLBP-related disability as assessed by the Oswestry Disability Index;⁶⁵ and being treated with > 15 mg/day of morphine-MG equivalent daily dose (MEDD) of opioids for > 3 months. Exclusion criteria included prior training in CBT or MBT, current pregnancy, active symptoms of a psychotic disorder within the past year, or inability to safely participate in the study. All participants were financially compensated.⁶²

Procedures

Following an initial screening, participants who met eligibility criteria and provided informed consent completed a baseline assessment, which included a battery of self-report measures assessing demographic and clinically relevant characteristics. Next, electrocardiogram (ECG) electrodes were attached to participants’ right and left pectoral muscles. Participants sat quietly for five minutes to allow their heart rates to acclimate to the testing environment and before completing a blocked ER task while ECG data were recorded. All participants were prescribed daily opioids and were instructed to take their medication as usual on the day of assessment to avoid cognitive, affective, or autonomic disruption associated with withdrawal.

Following this baseline assessment, participants were randomly assigned to one of two 8-week psychological interventions: MBT (n = 41) or CBT (n = 27). MBT taught mindfulness meditation techniques (e.g., mindful breathing, body scan) and emphasized cultivating nonjudgmental meta-awareness of present-moment experiences and acceptance-based coping for stress and pain. CBT focused on strategies such as cognitive restructuring, progressive muscle relaxation, and graded activity to promote a change-oriented approach to pain coping. Follow-up assessments occurred at 3, 6, 9, and 12 months after treatment initiation. All study procedures adhered to the standards proposed in the Helsinki Declaration of 1975 and were approved by the Institutional Review Boards of the institutions participating in the multisite trial.⁶² Details of each intervention and the study methods are described elsewhere.⁶²

Measures

Emotion Regulation Task

This study employed a well-validated ER paradigm,^66,67 in which participants viewed negative images (e.g., depictions of violence or injury) selected from the International Affective Picture System. Sixty images were displayed for 6 s each, separated by a 500-ms fixation cross. The images were presented in two 30-image blocks corresponding to one of two experimental conditions: “view negative” and “reappraise negative.” During the “view negative” block, participants were instructed to observe the image without trying to alter their emotional experience. During the “reappraise negative” block, participants were instructed to reinterpret the meaning of the image content (e.g., imagining a positive outcome, reconstruing the challenge portrayed in the image as an opportunity for personal growth etc.) to reduce their emotional reaction to the image.

Prior to the ER task, participants completed a brief training session in which they were asked to verbally describe their experience practicing the “view negative” and “reappraise negative” instructions. Participants were permitted to proceed to the task only after verbally demonstrating the ability to correctly follow both sets of instructions.

Heart Rate Variability

To assess HF-HRV during the ER task, Ag–AgCl electrodes were attached to participants’ right and left pectoral muscles and ECG data were sampled at 1000 Hz and recorded continuously using a Biopac MP150 (Biopac, Goleta, CA). The metric of interest was HF-HRV in the respiratory frequency band of 0.15–0.40 Hz. Respiration rate was concurrently monitored via the Biopac system to confirm it remained within this frequency range. Heart rate, determined by R-R wave intervals in the ECG, was initially detected automatically using Acqknowledge 4.1 software and then visually inspected to correct any misidentified or omitted R-waves. Kubios 2.0⁶⁸ was used to compute heart rate-per-minute and for spectral analysis of R-waves. R-R interval data were divided into two 3.25-min segments corresponding to the “view negative” and “reappraise negative” conditions. HF-HRV analyses were performed on the entire segment length of each condition, applying a fast Fourier transformation to extract normalized HF-HRV from a de-trended, end-tapered interbeat interval time series. The spectrum for the selected R-R interval segment was calculated via Welch’s periodogram method, in which R-R interval data were reduced using Kubios 2.0 default settings of a window width of 128 s (with a window overlap of 50%).⁶⁹

Analysis of respiration frequency data showed that breathing rate of participants during the ER task fell within the recommended respiratory frequency band. Following Berntson et al.⁷⁰ and Malliani, Lombardi, and Pagani,⁷¹ HF-HRV was calculated in normalized units to elucidate shifts in its frequency component that might otherwise be obscured by use of absolute units, which are dependent on total HF-HRV power. Normalization of HF-HRV values yields statistical averages with distributions that converge more readily to normal distributions than do raw spectral band powers while producing values that facilitate comparisons across studies employing similar tasks with different block lengths.⁷² HF-HRV was averaged across the 5-minute resting baseline and the two ER task blocks.

Self-Reported Cognitive Reappraisal

Self-reported cognitive reappraisal was measured using the 6-item reappraisal subscale of the Emotion Regulation Questionnaire (ERQ).⁷³ Items assess the tendency to use cognitive reappraisal to reduce negative emotional experiences in daily life on a scale ranging from 1 (strongly disagree) to 7 (strongly agree), and were summed to compute a total score (α = .91).

Pain Interference

Pain-related functional interference was assessed using the 7-item pain interference subscale of the Brief Pain Inventory (BPI), a widely used and well-validated measure of acute and chronic pain.⁶⁴ Participants rated the extent to which pain had interfered with seven domains of functioning over the past week on a scale from 0 (does not interfere) to 10 (completely interferes). Item means were computed to create an overall score.

Average Pain Severity

Average pain severity was measured using a single item from the BPI that asked participants to rate their average pain over the past week on a scale from 0 (no pain) to 10 (pain as bad as you can imagine).¹²

Opioid Dose

Daily opioid dose was assessed using the Timeline Followback method, a validated approach for capturing daily substance use with strong test–retest reliability.⁷⁴ Participants reported all doses of all opioids over the past 14 days, which were converted to morphine equivalent daily dose (MEDD) using published conversion factors.⁷⁵

Data Analysis

Analysis began by computing an index of HF-HRV cognitive reappraisal efficacy by subtracting HF-HRV during the “view negative” condition from HF-HRV during the “reappraise negative” condition. Computation of baseline reappraisal efficacy via a difference score is the standard approach for physiological research on negative emotion regulation.^{61,67,76–78} Higher values of this difference score reflect larger increases in phasic HF-HRV, and were interpreted as indicating increased capacity to engage cognitive reappraisal. After computing this index, the association between HF-HRV during the reappraisal task and self-reported reappraisal on the ERQ was tested by calculating the zero-order correlation between the two variables.

Next, linear mixed-effects repeated measures analyses of covariance were employed to examine whether baseline HF-HRV cognitive reappraisal efficacy (i.e., the difference score) predicted baseline-adjusted posttreatment changes in average pain severity and pain interference, controlling for opioid dose. Models included random intercepts and fixed effects for cognitive reappraisal, pre-randomization baseline values of each respective outcome, treatment condition (MBT vs. CBT), opioid dose, and time (3-, 6-, 9-, and 12-month follow-up assessments). The primary fixed effect of interest was the adjusted main effect of reappraisal, which estimates the overall impact of baseline reappraisal efficacy on pain severity and interference averaged across all follow-up assessments.

To evaluate potential treatment-specific effects, a supplementary set of exploratory analyses was conducted in which the two primary models were re-estimated with the addition of a cognitive reappraisal X treatment condition interaction term. The primary fixed effect of interest was the interaction term, which tested whether baseline cognitive reappraisal efficacy differentially predicted pain severity and interference in the MBT versus CBT conditions.

To examine patterns of missing data, Little’s Missing Completely at Random test was conducted,⁷⁹ which indicated that the data were consistent with the assumption of being missing completely at random (χ² = 75.4, df = 94, p = .920). As such, missing data were managed using maximum likelihood estimation.¹⁷ Analyses were conducted in RStudio (Version 1.2.5033) using the nlme package to estimate linear mixed-effects models.⁸⁰

Results

Participants

Table 1 provides demographic and clinical characteristics of the study sample (N = 68). The mean age of participants was 58.3 years (standard deviation [SD] = 10.9), and the majority identified as female (60.3%) and White (89.7%). Most participants (82.4%) reported educational attainment beyond a high school degree, and over one-third (36.8%) reported annual household incomes below $25,000. The baseline median MEDD was 60 mg/day (SD = 149.5; interquartile range [IQR] = 88.1 mg), with 36.7% of participants reporting being treated with at least 90 mg per day. There were no significant correlations between HF-HRV reappraisal efficacy and self-reported reappraisal (r = −0.16, p = .227) as measured by the reappraisal subscale of the ERQ.

Linear Mixed-Effects Models

Results from the linear mixed-effects models (see Table 2) revealed a significant effect of HF-HRV cognitive reappraisal efficacy on pain severity (F_1,63 = 5.35, p = .024, β = −0.001, 95% confidence interval [CI]: −0.002, −0.0002) and pain interference (F_1,63 = 4.93, p = .030, β = – 0.002, 95% CI: −0.004, −0.0002). These findings suggest that lower HF-HRV reappraisal efficacy at baseline predicted higher levels of both pain-related outcomes across the 12-month follow-up period irrespective of treatment condition (see Figures 1 and 2). However, treatment condition was not significantly associated with pain severity (F_1,63 = 3.38, p = .071, β = 0.49, 95% CI: −0.04, 1.23) or interference (F_1,63 = 2.35, p = .131, β = −0.66, 95% CI: −0.20, 1.53).

Table 2.

Tests of fixed effects for linear mixed-effects models assessing changes in pain severity and pain interference

Fixed Effects	df	F	p	β	95% CI
Pain Severity
Intercept	1, 153	22.05	<.001	3.02	1.75, 4.29
Cognitive reappraisal efficacy (HF-HRV)	1, 63	5.35	.024	−.001	−0.002, −0.0002
Baseline pain severity	1, 63	18.69	<.001	0.42	0.23, 0.62
Treatment condition (MBT vs. CBT)	1, 63	3.38	.071	0.49	−0.04, 1.03
Opioid dose	1, 63	1.15	.288	0.001	−0.001, 0.003
Time	3, 153	0.62	.605
6 months vs. 3 months			.190	−0.24	−0.58, 0.11
9 months vs. 3 months			.442	−0.15	−0.51, 0.22
12 months vs. 3 months			.425	−0.18	−0.61, 0.25
Pain Interference
Intercept	1, 153	48.40	<.001	4.23	3.03, 5.43
Cognitive reappraisal efficacy (HF-HRV)	1, 63	4.93	.030	−.002	−0.003, −0.0002
Baseline pain interference	1, 63	75.65	<.001	0.35	0.27, 0.42
Opioid dose	1, 63	1.11	.297	.002	−0.001, 0.004
Treatment condition (MBT vs. CBT)	1, 63	2.35	.131	0.66	−0.20, 1.53
Time	3, 153	1.03	.384
6 months vs. 3 months			.093	−0.85	−1.83, 0.12
9 months vs. 3 months			.192	−0.81	−2.02, 0.39
12 months vs. 3 months			.255	−0.66	−1.77, 0.46

Note. MBI = mindfulness-based therapy, CBT = cognitive behavioral therapy, CI = confidence interval. Pain severity and pain interference were assessed using the Brief Pain Inventory. Cognitive reappraisal was indexed by high-frequency heart rate variability (HF-HRV) measured during an emotion regulation task (reappraisal efficacy = view negative - reappraise negative).

Figure 1.

Average pain severity scores at 3-, 6-, 9-, and 12-month follow-up assessments. Linear mixed-effects modeling testing baseline cognitive reappraisal efficacy showed that lower cognitive reappraisal efficacy, indexed via high-frequency heart rate variability during an emotion regulation task, predicted greater pain severity across the 12-month follow-up, as measured by the Brief Pain Inventory. No significant effects were observed for treatment condition. The model was adjusted for baseline pain severity. Error bars represent standard errors.

Figure 2.

Pain interference scores at 3-, 6-, 9-, and 12-month follow-up assessments. Linear mixed-effects modeling testing baseline cognitive reappraisal efficacy showed that lower cognitive reappraisal efficacy, indexed via high-frequency heart rate variability during an emotion regulation task, predicted greater pain interference across the 12-month follow-up, as measured by the Brief Pain Inventory. No significant effects were observed for treatment condition. The model was adjusted for baseline pain interference. Error bars represent standard errors.

In the second set of models testing for moderation, the HF-HRV cognitive reappraisal efficacy X treatment condition interaction was not significant for either pain severity (F_1,62 = 1.20, p = .278, β = −0.001, 95% CI: −0.004 – 0.001), or pain interference (F_1,62 = 0.85, p = .360, β = −0.002, 95% CI: −0.006, 0.002), indicating that the effect of baseline reappraisal efficacy on pain outcomes did not significantly differ between treatment conditions.

Discussion

ER is recognized as a critical component of chronic pain management, yet it is unknown whether cognitive reappraisal efficacy influences the outcomes of psychological pain treatments. Current theories suggest that higher HF-HRV reflects greater autonomic control, facilitating adaptive ER in the face of stressors that may positively influence pain outcomes.^53,54 The present exploratory study investigated this relationship by examining this physiological marker as a predictor of pain severity and interference among adults with opioid-treated CLBP treated with MBT or CBT. Consistent with results from the parent clinical trial from which the present data are derived, both CBT and MBT significantly reduced pain severity and interference over time; however, no significant differences emerged between treatment conditions. Additionally, no significant interaction was found between reappraisal efficacy and treatment condition.⁶³ However, lower baseline reappraisal efficacy, as measured via blunted increases in HF-HRV during a cognitive reappraisal task, predicted smaller improvements in pain severity and interference across the 12-month follow-up, regardless of treatment modality.

Study findings offer insights into the potential mechanisms linking ER and chronic pain. HF-HRV is widely regarded as a biomarker of self-regulatory capacity, including the ability to downregulate negative emotions, for example, via reappraisal.⁵⁷ According to the neurovisceral integration model, these regulatory processes are supported by the central autonomic network, an interconnected circuit of neural regions governed by the prefrontal cortex, which exerts inhibitory control over subcortical structures and cardiac vagal tone as expressed by HF-HRV.^52,54 Attenuated HF-HRV during reappraisal may therefore signal disrupted central-autonomic integration and impairments in top-down cognitive control over bottom-up affective responses—processes critical for regulating emotions and pain.^{28,53,58,81,82} Such disruptions may perpetuate negative emotional states and maladaptive responses to stress and pain, which have been shown to amplify pain severity and functional impairment even following evidence-based treatments.^18,24,29,83 This interpretation aligns with studies demonstrating that chronic pain conditions are frequently associated with autonomic dysfunction marked by lower HF-HRV.^84,85 Emotional dysregulation is thought to contribute to this blunted parasympathetic response,^52,86–88 which is associated with greater pain severity, functional impairment, and worse treatment response.^84,89,90

Study findings further suggest that diminished reappraisal capacity may be a risk factor for worse chronic pain treatment outcomes. This is consistent with prior research linking self-reported emotional dysregulation to greater pain severity^{18,24,29,83,91} and reduced treatment efficacy.^92–95 It is also in line with evidence demonstrating that greater self-reported use of reappraisal is associated with lower pain severity and interference,^24,25 and that increases in self-reported reappraisal over the course of treatment predict better pain-related outcomes.⁹⁶ Extending this research, this study utilized a performance-based, psychophysiological measure of reappraisal to examine its association with treatment response over a long-term follow-up among adults with opioid-treated CLBP. Study results suggest that compromised regulatory functioning at baseline may serve as a prognostic indicator of pain-related outcomes, offering new avenues for targeted, personalized treatment.

As a secondary analysis of a small subsample from a larger RCT, findings should be considered exploratory and interpreted with several limitations in mind. The generalizability of study findings may be constrained by the use of HF-HRV as the sole psychophysiological measure of reappraisal capacity. Notably, no significant relationship was observed between HF-HRV and self-reported reappraisal on the ERQ. Although some studies have found positive associations between HRV and self-reported ER strategies like reappraisal,^97,98 null findings have also been reported,^99,100 which may reflect the fact that these measures capture distinct regulatory processes. In the present study, HF-HRV was assessed during a validated, performance-based ER paradigm and reflects the ability to proactively modulate autonomic responding during emotional provocation. By contrast, the ERQ reappraisal subscale indexes the frequency with which individuals report using reappraisal in daily life.⁷³ Retrospectively assessed self-reported frequency of reappraisal use may be distinct from the ability to engage reappraisal in response to a present negative emotional stimulus. Future studies should employ a multimodal approach incorporating performance-based assessments and psychophysiological reappraisal metrics beyond HF-HRV.

Additionally, the ER paradigm employed in the present study, while well-validated,^66,67 focused solely on cognitive reappraisal, which is just one of many ER strategies. Research demonstrates that even putatively adaptive strategies such as reappraisal are not universally effective in the regulation of negative affect; rather, their utility varies across individual characteristics and contextual factors, including the nature of the information being reappraised.^101–103 Further research should examine reappraisal alongside other ER strategies to clarify for whom, and under what circumstances, different strategies are most beneficial. Of particular relevance to MBT is pain acceptance, which has been shown to exert beneficial effects on pain outcomes.^104,105

Other factors might have also influenced the relationship between ER and pain. For instance, prior studies have found that when ER strategies are unsuccessful, pain severity may be impacted by the continued use of maladaptive ER strategies like pain catastrophizing.⁹ Additional confounders not accounted for in this analysis, such as trauma exposure and opioid misuse, may have also influenced autonomic function and HF-HRV.^31,106 Similarly, although analyses were adjusted for participants’ daily opioid dose, the timing of dosing on the day of the laboratory protocol was not assessed. To minimize potential withdrawal-related autonomic effects, participants were instructed to take their opioid medication as prescribed on the day of assessment. Nevertheless, variability in dosing timing may have impacted HF-HRV responses given the known effects of opioids on parasympathetic activity.

The modest sample size may have also limited statistical power to detect significant effects of treatment or treatment condition X reappraisal efficacy interactions. While the absence of a significant treatment effect aligns with findings from the parent trial,⁶³ replication in larger samples is needed to further examine whether treatment condition moderates the relationship between reappraisal efficacy and pain outcomes. The study sample was also predominantly Caucasian, further limiting generalizability. Given that the use, frequency, and adaptive value of emotion regulation strategies, including cognitive reappraisal, have been shown to vary across cultural contexts, replication in more racially and culturally diverse samples is needed.¹⁰⁷

HF-HRV was also unable to be assessed following treatment due to the onset of the COVID-19 pandemic, which necessitated shifting toward a fully remote study and abandoning in-person assessments such as the HF-HRV task. Future studies should assess whether changes in reappraisal efficacy from pre- to post-treatment mediate the effects of MBT or CBT. Finally, although multiple analyses were conducted, no corrections were applied for multiple comparisons in this exploratory study to minimize the risk of Type II errors. As a result, findings should be interpreted with caution given the potential for inflated false-positive results.

Despite these limitations, study findings hold important implications for the development and refinement of interventions aimed at improving ER in adults with chronic pain. Study results suggest that, regardless of intervention modality, greater emphasis on enhancing ER through the cultivation of adaptive ER skills is warranted in psychological chronic pain treatments. Emotion dysregulation is increasingly recognized as a key transtherapeutic treatment target for individuals with chronic pain,^24,108 and multiple RCTs show that interventions explicitly focused on enhancing ER can improve pain-related intensity and interference.^109,110 Accordingly, more explicit incorporation of ER skill-building into psychological treatments may be necessary to facilitate sustained improvements in pain-related outcomes.

CBT and MBT are commonly used treatments for chronic pain, yet they approach ER through distinct mechanisms. Whereas cognitive reappraisal is a core strategy used in CBT to alleviate psychological distress,³² MBT commonly emphasizes mindfulness practices aimed at fostering non-judgmental awareness and acceptance to reduce emotional reactivity.³³ Notably, while most MBTs for chronic pain do not include explicit training in reappraisal techniques, studies suggest that mindfulness training may nevertheless augment this skill.^38,39 Moreover, evidence suggests that integrating mindfulness training with ER techniques like cognitive reappraisal, may be an especially potent means of improving pain-related outcomes.³⁶

In that regard, Mindfulness-Oriented Recovery Enhancement (MORE) is a multimodal intervention that combines mindfulness training, CBT, and positive psychology principles in a sequenced program designed to address chronic pain, opioid misuse, and psychiatric distress.¹¹¹ Unlike other MBTs, MORE explicitly incorporates cognitive-affective techniques, including reappraisal, to address emotion dysregulation. Multiple RCTs have demonstrated that MORE enhances self-reported reappraisal capacity while decreasing chronic pain symptoms,^112–116 with effects lasting as long as nine months after treatment.¹¹⁷ MORE has also been shown to improve physiological markers of reappraisal efficacy, such as skin conductance, providing evidence for its ability to attenuate sympathetic reactivity to negative emotional stimuli.¹¹⁶ The MBT assessed in the present study was adapted from several established mindfulness-based programs, including MORE.⁶² Future studies should test whether combining mindfulness training with reappraisal skills might enhance HF-HRV and improve chronic pain treatment outcomes.

In conclusion, the current longitudinal study demonstrated that autonomic indices of reappraisal at baseline can predict chronic pain treatment outcomes for as long as 12-months, adding to the growing body of literature highlighting the importance of ER for chronic pain management. Given that reappraisal was associated with reduced pain severity and interference among adults with opioid-treated CLBP, interventions that strengthen ER might be especially efficacious in this population. Ultimately, a broader understanding of the relationship between ER and pain outcomes is needed to develop targeted, personalized, effective interventions for this vulnerable population.

Perspective:

This study found that lower baseline cognitive reappraisal efficacy, indexed by blunted HF-HRV during an emotion regulation task, predicted worse response to psychological treatment for adults with opioid-treated CLBP. These findings point to the potential importance of cognitive reappraisal as a therapeutic target in chronic pain interventions.

Highlights.

• Emotion regulation capacity (ER, e.g. reappraisal) may affect chronic pain treatment outcomes.

• Cognitive behavioral therapy and mindfulness-based therapy improved pain severity and interference.

• Lower heart rate variability during reappraisal predicted poorer outcomes for both interventions.

• Enhancing ER may strengthen autonomic functioning and improve pain-related treatment outcomes.