Who Benefits the Most From Different Psychological Chronic Pain Treatments? An Exploratory Analysis of Treatment Moderators.

Different psychological chronic pain treatments benefit some individuals more than others. Understanding the factors that are associated with treatment response-especially when those factors differ between treatments-may inform more effective patient-treatment matching. This study aimed to identify variables that moderate treatment response to 4 psychological pain interventions in a sample of adults with low back pain or chronic pain associated with multiple sclerosis, spinal cord injury, acquired amputation, or muscular dystrophy (N = 173). The current study presents the results from secondary exploratory analyses using data from a randomized controlled clinical trial which compared the effects of 4 sessions of cognitive therapy (CT), hypnosis focused on pain reduction (HYP), hypnosis focused on changing pain-related cognitions and beliefs (HYP-CT), and a pain education control condition (ED). The analyses tested the effects of 7 potential treatment moderators. Measures of primary (pain intensity) and secondary (pain interference, depression severity) outcome domains were administered before and after the pain treatments, and potential moderators (catastrophizing, hypnotizability, and electroencephalogram (EEG)-assessed oscillation power across five bandwidths) were assessed at pre-treatment. Moderator effects were tested fitting regression analyses to pre- to post-treatment changes in the three outcome variables. The study findings, while preliminary, support the premise that pre-treatment measures of hypnotizability and EEG brain activity predict who is more (or less) likely to respond to different psychological pain treatments. If additional research replicates the findings, it may be possible to better match patients to their more individually suitable treatment, ultimately improving pain treatment outcomes. PERSPECTIVE: Pre-treatment measures of hypnotizability and EEG-assessed brain activity predicted who was more (or less) likely to respond to different psychological pain treatments. If these findings are replicated in future studies, they could inform the development of patient-treatment matching algorithms.

Effects of hypnosis vs mindfulness meditation vs education on chronic pain intensity and secondary outcomes in veterans: a randomized clinical trial.

ABSTRACT: Effective, rigorously evaluated nonpharmacological treatments for chronic pain are needed. This study compared the effectiveness of training in hypnosis (HYP) and mindfulness meditation (MM) with an active education control (ED). Veterans (N = 328) were randomly assigned to 8 manualized, group-based, in-person sessions of HYP (n = 110), MM (n = 108), or ED (n = 110). Primary (average pain intensity [API]) and secondary outcomes were assessed at pretreatment, posttreatment, and 3 and 6 months posttreatment. Treatment effects were evaluated using linear regression, a generalized estimating equation approach, or a Fisher exact test, depending on the variable. There were no significant omnibus between-group differences in pretreatment to posttreatment change in API; however, pretreatment to posttreatment improvements in API and several secondary variables were seen for participants in all 3 conditions. Participation in MM resulted in greater decreases in API and pain interference at 6 months posttreatment relative to ED. Participation in HYP resulted in greater decreases in API, pain interference, and depressive symptoms at 3 and 6 months posttreatment compared with ED. No significant differences on outcomes between HYP and MM were detected at any time point. This study suggests that all 3 interventions provide posttreatment benefits on a range of outcomes, but the benefits of HYP and MM continue beyond the end of treatment, while the improvements associated with ED dissipate over time. Future research is needed to determine whether the between-group differences that emerged posttreatment are reliable, whether there are benefits of combining treatments, and to explore moderating and mediating factors.

Pain-related beliefs, cognitive processes, and electroencephalography band power as predictors and mediators of the effects of psychological chronic pain interventions.

ABSTRACT: The current study used data from a clinical trial to identify variables that are associated with and/or mediate the beneficial effects of 4 psychological chronic pain treatments: one teaching patients self-hypnosis to reduce pain intensity (HYP), one teaching self-hypnosis to change thoughts about pain (hypnotic cognitive therapy [HYP-CT]), one teaching cognitive restructuring skills to change thoughts about pain (cognitive therapy [CT]), and one providing education about pain (ED; included as an active control condition). Of 17 possible mechanism variables examined, and with alpha not corrected for multiple comparisons, significant between-group differences were observed for 3. Two of these (changes in beliefs about control over pain and number of days of skill practice) were supported as mediators of the beneficial effects of HYP, CT, or HYP-CT, relative to ED. Six mechanism variables evidenced significant pretreatment to post-treatment changes in the sample as a whole, without showing significant between-group differences. Pretreatment to post-treatment changes in all 6 were associated with improvements in pain interference, pain intensity, or both. In addition, participant ratings of therapeutic alliance at post-treatment were associated significantly with improvements in both pain intensity and pain interference in the sample as a whole. Thus, of the 17 possible mediators examined, there were relatively few that served as mediators for the beneficial effects of specific treatments; a larger number of variables predicted treatment outcome overall. The extent to which these variables are treatment mediators (ie, are responsible for, rather than merely associated with, treatment-related improvements) will require further research.

Effects of hypnosis, cognitive therapy, hypnotic cognitive therapy, and pain education in adults with chronic pain: a randomized clinical trial.

Chronic pain is a significant health problem worldwide with limited pharmacological treatment options. This study evaluated the relative efficacy of 4 treatment sessions each of 4 nonpharmacological treatments: (1) hypnotic cognitive therapy (using hypnosis to alter the meaning of pain); (2) standard cognitive therapy; (3) hypnosis focused on pain reduction, and (4) pain education. One hundred seventy-three individuals with chronic pain were randomly assigned to receive 4 sessions of 1 of the 4 treatments. Primary (pain intensity) and secondary outcome measures were administered by assessors unaware of treatment allocation at pretreatment, posttreatment, and 3-, 6-, and 12-month follow-up. Treatment effects were evaluated using analysis of variance, a generalized estimating equation approach, or a Fisher exact test, depending on the outcome domain examined. All 4 treatments were associated with medium to large effect size improvements in pain intensity that maintained up to 12 months posttreatment. Pretreatment to posttreatment improvements were observed across the 4 treatment conditions on the secondary outcomes of pain interference and depressive symptoms, with some return towards pretreatment levels at 12-month follow-up. No significant between-group differences emerged in omnibus analyses, and few statistically significant between-group differences emerged in the planned pairwise analyses, although the 2 significant effects that did emerge favored hypnotic cognitive therapy. Future research is needed to determine whether the significant differences that emerged are reliable.

The chronic pain skills study: Protocol for a randomized controlled trial comparing hypnosis, mindfulness meditation and pain education in Veterans.

OBJECTIVES: To describe the protocol of a randomized controlled trial to evaluate the effectiveness and mechanisms of three behavioral interventions. METHODS: Participants will include up to 343 Veterans with chronic pain due to a broad range of etiologies, randomly assigned to one of three 8-week manualized in-person group treatments: (1) Hypnosis (HYP), (2) Mindfulness Meditation (MM), or (3) Education Control (EDU). PROJECTED OUTCOMES: The primary aim of the study is to compare the effectiveness of HYP and MM to EDU on average pain intensity measured pre- and post-treatment. Additional study aims will explore the effectiveness of HYP and MM compared to EDU on secondary outcomes (i.e., pain interference, sleep, depression, anxiety and PTSD), and the maintenance of effects at 3- and 6-months post-treatment. Participants will have electroencephalogram (EEG) assessments at pre- and post-treatment to determine if the power of specific brain oscillations moderate the effectiveness of HYP and MM (Study Aim 2) and examine brain oscillations as possible mediators of treatment effects (exploratory aim). Additional planned exploratory analyses will be performed to identify possible treatment mediators (i.e., pain acceptance, catastrophizing, mindfulness) and moderators (e.g., hypnotizability, treatment expectations, pain type, cognitive function). SETTING: The study treatments will be administered at a large Veterans Affairs Medical Center in the northwest United States. The treatments will be integrated within clinical infrastructure and delivered by licensed and credentialed health care professionals.

Brain Oscillations, Hypnosis, and Hypnotizability.

This article summarizes the state-of-science knowledge regarding the associations between hypnosis and brain oscillations. Brain oscillations represent the combined electrical activity of neuronal assemblies, usually measured as specific frequencies representing slower (delta, theta, alpha) and faster (beta, gamma) oscillations. Hypnosis has been most closely linked to power in the theta band and changes in gamma activity. These oscillations are thought to play a critical role in both the recording and recall of declarative memory and emotional limbic circuits. The authors propose that this role may be the mechanistic link between theta (and perhaps gamma) oscillations and hypnosis, specifically, that the increases in theta oscillations and changes in gamma activity observed with hypnosis may underlie some hypnotic responses. If these hypotheses are supported, they have important implications for both understanding the effects of hypnosis and for enhancing response to hypnotic treatments.

Brain Oscillations, Hypnosis, and Hypnotizability.

In this article, we summarize the state-of-science knowledge regarding the associations between hypnosis and brain oscillations. Brain oscillations represent the combined electrical activity of neuronal assemblies, and are usually measured as specific frequencies representing slower (delta, theta, alpha) and faster (beta, gamma) oscillations. Hypnosis has been most closely linked to power in the theta band and changes in gamma activity. These oscillations are thought to play a critical role in both the recording and recall of declarative memory and emotional limbic circuits. Here we propose that it is this role that may be the mechanistic link between theta (and perhaps gamma) oscillations and hypnosis; specifically that theta oscillations may facilitate, and that changes in gamma activity observed with hypnosis may underlie, some hypnotic responses. If these hypotheses are supported, they have important implications for both understanding the effects of hypnosis, and for enhancing response to hypnotic treatments.

Baseline brain activity predicts response to neuromodulatory pain treatment.

OBJECTIVES: The objective of this study was to examine the associations between baseline electroencephalogram (EEG)-assessed brain oscillations and subsequent response to four neuromodulatory treatments. Based on available research, we hypothesized that baseline theta oscillations would prospectively predict response to hypnotic analgesia. Analyses involving other oscillations and the other treatments (meditation, neurofeedback, and both active and sham transcranial direct current stimulation) were viewed as exploratory, given the lack of previous research examining brain oscillations as predictors of response to these other treatments. DESIGN: Randomized controlled study of single sessions of four neuromodulatory pain treatments and a control procedure. METHODS: Thirty individuals with spinal cord injury and chronic pain had their EEG recorded before each session of four active treatments (hypnosis, meditation, EEG biofeedback, transcranial direct current stimulation) and a control procedure (sham transcranial direct stimulation). RESULTS: As hypothesized, more presession theta power was associated with greater response to hypnotic analgesia. In exploratory analyses, we found that less baseline alpha power predicted pain reduction with meditation. CONCLUSIONS: The findings support the idea that different patients respond to different pain treatments and that between-person treatment response differences are related to brain states as measured by EEG. The results have implications for the possibility of enhancing pain treatment response by either 1) better patient/treatment matching or 2) influencing brain activity before treatment is initiated in order to prepare patients to respond. Research is needed to replicate and confirm the findings in additional samples of individuals with chronic pain.

Effects of non-pharmacological pain treatments on brain states.

OBJECTIVE: To (1) evaluate the effects of a single session of four non-pharmacological pain interventions, relative to a sham tDCS procedure, on pain and electroencephalogram- (EEG-) assessed brain oscillations, and (2) determine the extent to which procedure-related changes in pain intensity are associated with changes in brain oscillations. METHODS: 30 individuals with spinal cord injury and chronic pain were given an EEG and administered measures of pain before and after five procedures (hypnosis, meditation, transcranial direct current stimulation [tDCS], neurofeedback, and a control sham tDCS procedure). RESULTS: Each procedure was associated with a different pattern of changes in brain activity, and all active procedures were significantly different from the control procedure in at least three bandwidths. Very weak and mostly non-significant associations were found between changes in EEG-assessed brain activity and pain. CONCLUSIONS: Different non-pharmacological pain treatments have distinctive effects on brain oscillation patterns. However, changes in EEG-assessed brain oscillations are not significantly associated with changes in pain, and therefore such changes do not appear useful for explaining the benefits of these treatments. SIGNIFICANCE: The results provide new findings regarding the unique effects of four non-pharmacological treatments on pain and brain activity.

Steps toward developing an EEG biofeedback treatment for chronic pain.

Chronic pain, usually refractory to analgesics, is a significant problem for many individuals with spinal cord injury (SCI). Preliminary studies suggest that electroencephalography (EEG) biofeedback (also known as neurofeedback, NF) has the potential to help patients with otherwise refractory chronic pain. However, there remain many unanswered questions about the effects and mechanisms of this treatment. We studied 13 individuals with SCI and chronic pain with NF. Ten of the 13 individuals completed 4 sessions each of three different neurofeedback protocols assigned in random order for a total of 12 NF sessions. All three protocols had similar immediate effects on pain intensity. In addition, the participants reported modest pre- to post-treatment decreases in worst pain and pain unpleasantness following completion of the 12 NF sessions. These improvements were maintained at 3-month follow-up. The majority of the participants felt they benefited from and were satisfied with the treatment. No significant effects on measures of other outcome domains (sleep quality, pain interference and fatigue) were observed, although there was a non-significant trend for an increase in fatigue. Finally, pre- to post-treatment changes in EEG bandwidth activity, consistent with the training protocols, were observed in θ and α but not ß frequencies. The findings provide preliminary support for the potential efficacy of NF for the treatment of SCI-related pain, and suggest that further clinical studies are warranted.

New insights into neuromodulatory approaches for the treatment of pain.

UNLABELLED: Two lines of evidence about the association between the experience of pain and brain state (measured via electroencephalogram or EEG) have recently come to light. First, research from a number of sources suggests a link between brain EEG activity and the experience of pain. Specifically, this research suggests that the subjective experience of pain is associated with relatively lower amplitudes of slower wave (delta, theta, and alpha) activity and relatively higher amplitudes of faster wave (beta) activity. Second, there has been a recent increase in interest in interventions that impact the cortical neuromodulation of pain, including behavioral treatments (such as self-hypnosis training and neurofeedback) and both invasive and noninvasive brain stimulation. Although a direct causal link between experience of pain and brain activity as measured by EEG has not been established, the targeting of pain treatment at a cortical level by trying to affect EEG rhythms directly is an intriguing possibility. PERSPECTIVE: Preliminary evidence suggests the possibility, which has not yet adequately tested or proven, that the experience of chronic pain is linked to cortical activity as assessed via an electroencephalogram. Support for this hypothesis would have important implications for understanding the mechanisms that underlie a number of pain treatments, and for developing new innovative treatments for chronic pain management.