Conscious connected breathing with breath retention intervention in adults with chronic low back pain: protocol for a randomized controlled pilot study
Pilot and Feasibility Studies volume 9, Article number: 15 (2023)
Chronic pain is a major source of human suffering, and chronic low back pain (cLBP) is among the most prevalent, costly, and disabling of pain conditions. Due to the significant personal and societal burden and the complex and recurring nature of cLBP, self-management approaches that can be practiced at home are highly relevant to develop and test. The respiratory system is one of the most integrated systems of the body, and breathing is bidirectionally related with stress, emotion, and pain. Thus, the widespread physiological and psychological impact of breathing practices and breathwork interventions hold substantial promise as possible self-management strategies for chronic pain. The primary aim of the current randomized pilot study is to test the feasibility and acceptability of a conscious connected breathing with breath retention intervention compared to a sham control condition.
The rationale and procedures for testing a 5-day conscious connected breathing with breath retention intervention, compared to a deep breathing sham control intervention, in 24 adults (18–65 years) with cLBP is described. Both interventions will be delivered using standardized audio recordings and practiced over 5 days (two times in-person and three times at-home), and both are described as Breathing and Attention Training to reduce possible expectancy and placebo effects common in pain research. The primary outcomes for this study are feasibility and acceptability. Feasibility will be evaluated by determining rates of participant recruitment, adherence, retention, and study assessment completion, and acceptability will be evaluated by assessing participants’ satisfaction and helpfulness of the intervention. We will also measure other clinical pain, psychological, behavioral, and physiological variables that are planned to be included in a follow-up randomized controlled trial.
This will be the first study to examine the effects of a conscious connected breathing with breath retention intervention for individuals with chronic pain. The successful completion of this smaller-scale pilot study will provide data regarding the feasibility and acceptability to conduct a subsequent trial testing the efficacy of this breathing self-management practice for adults with cLBP.
Clinicaltrials.gov, identifier NCT04740710. Registered on 5 February 2021.
Chronic pain is a major public health problem. Chronic low back pain (cLBP), one of the most prevalent chronic pain conditions, affects more than 540 million people and is a leading cause of disability in the world [1, 2]. The significant direct (e.g., healthcare) and indirect costs (e.g., work disability, loss of productivity) associated with cLBP produce substantial personal and societal burden, which is expected to increase over the coming years [1, 3]. Although cLBP tends to resolve over time, there are high rates of recurrence and many people suffer indefinitely . Nonpharmacological interventions, including complementary and integrative approaches, continue to gain interest and are now recommended as first line treatments for cLBP [5, 6]. Due to the persistent, costly, and complex nature of cLBP, nonpharmacological self-management approaches rooted in the biopsychosocial model of chronic pain are of great interest to develop and test [3, 5, 7–16].
Self-management approaches include strategies or interventions that individuals can learn and apply on their own to prevent or relieve symptoms, such as pain or stress [17, 18]. These approaches empower individuals with tools, knowledge, or techniques to take an active role in their health and symptom self-management. This is in contrast to traditional healthcare models where a patient is a passive recipient of care (e.g., surgery). Some examples of self-management approaches for chronic pain include physical exercise, mindfulness meditation, diet, and the use of medical or non-medical devices (e.g., transcutaneous electrical nerve stimulation) [5, 19]. Research shows that people with chronic pain value self-management approaches that (1) they can engage in at-home or remotely, (2) they can apply while continuing their medication, (3) improve more than just pain symptoms (e.g., depression), and (4) have a low time burden [20, 21]. We propose that brief, daily breathing practices are promising self-management approaches to investigate as they align with stakeholder values and potentially offer a nonpharmacological, biopsychosocial, and scalable solution to reduce the global burden of cLBP.
There are a variety of breathwork interventions (i.e., conscious breathing practices) that may be helpful for managing and treating chronic pain [22–26]. For example, increasing evidence supports that slow deep breathing and paced breathing (e.g., respiratory biofeedback) can improve pain-related outcomes and mechanisms, including increased parasympathetic nervous system activity (i.e., heart rate variability), baroflex sensitivity, and relaxation, and decreased stress, anxiety, depression, negative affect, muscle tension, and experimental pain sensitivity [27–38]. These studies, however, primarily examine the effects of controlled breathing practices in healthy samples. Research on breathing practices for those with chronic back pain shows small-to-large effects for improving pain [23–25], but more randomized trials with rigorous methods are needed. Moreover, substantially less research has investigated other types of breathing interventions that may be more potent than slow deep breathing or other similar relaxation-based self-management practices (e.g., meditation) . Specifically, conscious connected breathing, a technique at the core of many different breathwork interventions [40–45], involves breathing with no pause between inhalation and exhalation (also known as circular breathing). Breathwork interventions that use conscious connected breathing often include other “add-on” components, such as mindful body awareness, music, or movement, that are believed to increase their efficacy . The breathing practice investigated in the current study combines conscious connected breathing with periods of breath holding, or breath retention.
The empirical research on conscious connected breathing with breath retention (CCBR) comes from an intervention that is often delivered by a specific teacher (i.e., Wim HofFootnote 1) within a group retreat setting and combined with additional components (e.g., cold exposure, visualization meditation, strength exercises) [47–50]. These aspects limit accessibility to the intervention and also complicate conclusions that can be drawn regarding the efficacy and mechanisms of the intervention due to the many potential specific and non-specific treatment effects [51–56]. Nevertheless, studies suggest that the breathing and retention practice alone can reduce stress  and induce profound physiological changes, including safe respiratory alkalosis (i.e., rise in pH levels), intermittent hypoxia, immediate changes in metabolic and hormonal activity (e.g., increased gluconeogenesis, human growth hormone), and increases in plasma epinephrine levels associated with sympathetic nervous system activation [47–49, 56, 58–60]. CCBR also seems to have significant effects on the immune system, demonstrated by an increase in anti-inflammatory and decrease in pro-inflammatory cytokines following the administration of an endotoxin [48, 56]. Furthermore, the full intervention that included cold exposure and strength exercises was shown safe and feasible for patients with axial spondyloarthritis, a chronic inflammatory disease characterized by pain, with preliminary evidence for reductions in systemic inflammation and disease severity . Yet, CCBR alone has not been tested for its impact on chronic pain, including in those with cLBP.
Consistent with models and recommendations for developing theoretically informed interventions [61, 62], several lines of evidence support the premise that CCBR will be helpful for individuals with chronic pain. First, both the volitional control of breathing and the specific type of rhythmic connected breathing and breath holding technique used in CCBR can elicit a cascade of biological and physiological responses that may reduce pain, such as improvements in heart rate variability (HRV) [26, 63, 64], baroreceptor sensitivity [65–68], acid-base balance (respiratory alkalosis) [69–71], periaqueductal gray structure and function [72–76], and immune and metabolic activity (e.g., inflammation) [47–49, 58, 77, 78]. Second, both the cyclical breathing and the breath retention may serve as a mild stressor (i.e., hormesis), like physical exercise, where the acute challenge to breathe deeper and hold one’s breath for longer than usual results in adaptive changes (e.g., stress resilience, preparation for oxidative stress, carbon dioxide tolerance) [41, 59, 79–84]. Third, conscious breathing exercises are likely to increase mindfulness and interoception (i.e., attention to and awareness of body, feelings, and homeostatic signals) [35, 85, 86]—both considered key factors for self-managing chronic pain as well as for improving overall mental and physical health [87–89]. Last, the extended breath retention (1–2.5 min) may induce intermittent hypoxia, which has been shown to lead to improved respiratory and non-respiratory motor function and neuroplasticity [90–92]. Enhanced neuroplasticity may open a therapeutic window that when combined with existing pain treatments, such as relaxation or mindful body awareness, can have synergistic effects in improving pain-related outcomes [92–97]. While this list is far from exhaustive, these possible mechanistic pathways provide compelling justification to scientifically investigate the physical and psychological effects of CCBR in those with chronic pain.
The purpose of the current pilot study is to evaluate whether it is feasible to conduct a clinical trial investigating CCBR for adults with cLBP in preparation for a subsequent, adequately powered randomized controlled trial (RCT) [98–101]. The primary objective is to test the feasibility and acceptability of 5 days of CCBR practice delivered via standardized audio recordings, compared to a structurally equivalent deep breathing sham control intervention [102–104], in a sample of 24 adults with cLBP. We expect it to be feasible to recruit, retain, and randomize participants to the intervention groups and expect at least 70% of participants to rate the interventions as acceptable and satisfying (≥ 7 out of 10). The secondary objective is to gather data regarding the plausibility that the CCBR intervention can result in clinically meaningful improvements in pain and pain-related variables [100, 105]. To demonstrate plausibility of improvement, we expect a greater ratio of participants in the CCBR group, compared to the control group, will meet the clinically significant treatment response target of ≥ 30% improvement in pre-post average pain intensity ratings [106–108]. A 30% reduction in pain is considered a moderately important change following treatment and is commonly used to determine clinical significance and/or treatment response in pain RCTs [107–111]. Results from this study will not be used to make claims about preliminary efficacy or to determine power for future sample size calculations [98, 100, 112] but rather to provide feasibility estimates, refine the interventions, and inform the successful design and implementation of an anticipated RCT, which will rigorously test the efficacy and mechanisms of this self-management breathing practice for adults with cLBP.
This parallel group, pilot RCT is designed to examine the feasibility and acceptability of a 5-day conscious connected breathing intervention that includes brief periods of breath retention, compared to a deep breathing sham control intervention, in a sample of adults with cLBP. The intervention length (5 sessions, 17-min per session) was chosen because previous research has demonstrated that mind-body interventions can influence physiological mechanisms of interest, such as central and autonomic nervous system functioning, after a similar period of training . Both interventions will be described as Breathing and Attention Training and neither will be depicted as the active therapeutic intervention (i.e., single-blind) in order to reduce possible expectancy and placebo effects common in pain research [102, 104, 114]. Participants will be randomly assigned at a 1:1 ratio to either the Standard-Breathing and Attention Training or the Focused-Breathing and Attention Training (BAT). The Standard-BAT is the sham control intervention, and the Focused-BAT is the active CCBR intervention. All participants will provide written and signed informed consent. The study was approved by the University of Florida Institutional Review Board, registered on clinicaltrials.gov (NCT04740710), and designed in accordance with CONSORT guidelines for reporting pilot RCTs [101, 115–117]. See Fig. 1 below for an overview of the study design.
Interested participants will complete a telephone screening to determine initial eligibility, and those who qualify will be scheduled for their first visit at the University of Florida Pain Clinical Research Unit to obtain informed consent and complete several baseline assessments and physical functioning tasks. At the end of Visit 1, participants will be scheduled for two additional study visits to occur within a 1-week period (pre-intervention and post-intervention). Participants will also be asked to complete two additional baseline surveys online using REDCap between Visit 1 and Visit 2, which is intended to reduce the participant burden and length of Visit 1. At Visit 2 (pre-intervention), participants will be randomized to the Standard- or Focused-BAT intervention before undergoing quantitative sensory testing procedures. Then, participants will be instructed via an audio-recording to practice their assigned breathing intervention for the first time with the researcher. Physiological data will be collected before, during, and after the breathing practice at both Visit 2 and Visit 3. Following Visit 2, participants will receive an email to practice BAT first thing in the morning if possible by following along to the recording on their own at home. If not possible to practice upon awakening, participants will be asked to practice at least 2 h after a meal. We will attempt to schedule intervention sessions over five consecutive days when possible (Monday–Friday). When not possible, we will require that the last at-home session and last in-person session (BAT sessions 4 and 5) be practiced on consecutive days. At Visit 3, participants will practice their assigned breathing intervention for the 5th and final time and then complete post-intervention questionnaires, quantitative sensory testing procedures, and physical functioning tasks. Finally, participants will be asked to complete 1-, 2-, and 3-month follow-up surveys online using REDCap.
With an estimated attrition rate of 20%, we are recruiting 30 participants between the ages of 18 and 65 with cLBP from the Gainesville, FL community to obtain complete data on 24 participants. We anticipate an additional 75 participants who undergo screening procedures will be ineligible for the study. The sample size was chosen to be large enough to achieve the primary objective (i.e., evaluating feasibility and acceptability) while also considering practical constraints, such as funding and time. Therefore, no power analysis was conducted. Participants will be compensated up to $245 for completing all study procedures. Inclusion and exclusion criteria are displayed in Table 1 and are consistent with definitions for chronic primary low back pain (e.g., back pain associated with emotional distress and/or functional disability and not better accounted for by another condition)  and recommendations of the NIH Task Force on Research Standards for cLBP (i.e., participants with cLBP of at least moderate impact that has persisted on more days than not over the past 6 months) .
Recruitment, screening, and enrollment
We will recruit for a “Breathe for Pain Study” widely throughout the Gainesville and University of Florida (UF) community to obtain a sufficient sample of eligible adults with cLBP. Recruitment flyers will be posted throughout the UF Campus (e.g., bulletin boards), as well as at local businesses (e.g., grocery stores), clinical settings (e.g., Clinical Research Center, Orthopedic Institute), and other locations recommended by the UF Clinical and Translational Science Institute Recruitment Center. The recruitment flyer and study information will also be posted online in relevant locations (e.g., The Pain Research and Intervention Center of Excellence Study Listings page). We will also call participants from UF registries, including HealthStreet a community engagement program that connects local residents with relevant research studies.
Potential participants will be screened over the phone using a standardized script. The phone screening involves briefly explaining the purpose of the study, collecting basic demographic and contact information, and determining initial eligibility. Interested and eligible participants will then schedule their first study visit where they will sign the informed consent form in person. Trained study staff will enter responses to the screening questions into a secure REDCap database.
Randomization and blinding
The principal investigator (S.P) generated the allocation sequence with a block size of two using an online random number generator (Random.org). Based on the allocation sequence, participants will be randomized (1:1 ratio) using the REDCap Randomization Module at the beginning of Visit 2 to either the Focused- or Standard-BAT. Participants will not be told which intervention they were randomized to until the end of the study, after the 3-month follow-up survey. Due to the inherent difficulties of blinding behavioral interventions, only the participant—not the researcher—will be blind to intervention assignment [102, 114, 120]. Effectiveness of participant blinding will be reported.
Breathing and Attention Training (BAT)
Participants are informed that they will be randomly assigned to either the Focused-Breathing and Attention Training or the Standard-Breathing and Attention Training. The consent form provides information that the Standard-BAT includes instruction on deep breathing and relaxation, and the Focused-BAT is similar to the Standard-BAT in most ways but includes extra instructions to help you focus and alter your breathing patterns. Thereafter, each intervention is referred to as BAT more generally to all participants in an attempt to evenly manage participant expectations and reduce potential placebo effects [102, 103, 121]. When first introducing the interventions to participants during Visit 2, they will receive the same information on the possible effects of BAT (see Additional file 1: Appendix 1).
Both interventions involve five separate, 17-min practice sessions of BAT. The first 12 min of both interventions include instructions to breathe in ways consistent with their assigned intervention, and both interventions include 5 min of silence at the end where participants are instructed to simply relax and lay still without modifying their breathing in any way. The interventions will be delivered via an audio recording in order to standardize the interventions across sessions and participants, thereby enhancing treatment fidelity through consistent intervention delivery. When practicing in-person, participants will remain reclined in a chair; when practicing at-home, participants will be instructed to lie down in a safe and comfortable position. Aside from the specific breathing instructions during the 12-min of BAT, all other aspects (e.g., setting, frequency, posture, facilitator) of the interventions will be identical [103, 104]. The scripts for each intervention are included in Additional file 1: Appendix 1.
Each session of the Focused-BAT intervention involves three rounds of conscious connected breathing and breath retention. For the breathing phase, participants are instructed to take about 40 deep connected breaths (no pause between inhale and exhale) at a rate of about 20 breaths per minute. The inhalation is encouraged to be deep into the abdomen (i.e., full breath in), and the exhalation is encouraged to be relaxed (i.e., let the breath go). For the breath retention phase, participants are instructed to hold their breath after the 40th exhale. The duration of the breath retention is at the discretion of the participant, but the audio recording prompts participants to inhale after approximately 1-, 1.5-, and 2-min for rounds 1–3, respectively, increasing the time of the breath hold each round. Although previous studies on this breathing practice have shown that breath retention was safe up to 3.5 min [47, 48], participants are clearly instructed to inhale when they feel an urge to breathe without forcing it or pushing beyond their limits (i.e., “just inhale when you need”). When the participant inhales to end the breath retention they are instructed to hold their breath again for 10–15 s. This process of deep connected breathing, extended breath retention after an exhale, and brief breath retention after an inhale is considered one round—participants practice three consecutive rounds of this procedure in a single session. In the first Focused-BAT session, the participant practices one round with the researcher to ensure understanding of the instructions before proceeding with the full three rounds. The guided audio recording includes inhale and exhale sounds to pace the breathing during the breathing phase and instructs participants to relax any areas of tightness, tension, or holding and to stay present and pay attention to their body and physical sensations during the breath retention phase (i.e., mindful body awareness).
Participants are told that the point of the Standard-BAT practice is to remain in an alert and attentive yet relaxed state by taking deep breaths every minute or so [122–124]. The recording first instructs participants to breathe in deeply through their nose for about 5 s and exhale slowly for about 5 s and to continue with this deep breathing on their own for the next minute. Then participants are told to allow their breathing to return to its normal and natural rhythm without trying to change it in anyway, remembering to take a few deep breaths every minute or so. About every minute or two, the audio recording prompts participants to take a couple of deep breaths and includes audible breathing sounds to pace the inhale and exhale. This intervention is designed to be similar in most aspects to the CCBR intervention except with different instructions on how to breathe or how to attend to one’s breathing. Thus, this group can truthfully be told that they have been randomly assigned to a breathing and attention training intervention without actually receiving instructions to bring attention to their body or alter their breathing pattern in a way similar to the CCBR group (i.e., connected breathing, breath holding, mindful body awareness). Previous research has shown this type of breathing and attention intervention decreases pain intensity and pain unpleasantness, but to a lesser degree than a comparable mindfulness meditation training  and slow breathing intervention . This Standard-BAT is also expected to be less potent than other deep breathing interventions because there are multiple periods of silence and few instructions on how to breathe, which is in contrast to other interventions that constantly cue participants to breathe deeply and rhythmically [27, 125]. Although some participants may maintain deep breathing on their own, the intervention is intended to induce natural, relaxed, spontaneous breathing.
At-home intervention adherence will be monitored by collecting data that tracks the length of time a participant stays on the intervention page of the survey that includes the guided audio recording. Specifically, we will assume the intervention was adhered to if a participant stays on the intervention page of the survey for at least 10 min.
Assessments and measures
Primary feasibility and acceptability outcomes
Feasibility and treatment acceptability are the primary outcomes of the proposed pilot study. Feasibility will be assessed by quantifying rates of participant recruitment, participant adherence, participant retention, and study assessments completion. Treatment acceptability and participant satisfaction will be assessed with several face-valid questions (e.g., How acceptable did you find this BAT treatment? How satisfied are you with this BAT treatment?) rated on a 11-point numerical rating scale (NRS) with anchors that match the content of each question (e.g., 0 = not at all acceptable, 10 = extremely acceptable). These assessments are described further in Additional file 1: Appendix 2 and are similar to those commonly used in other pilot feasibility studies to evaluate the acceptability of an intervention and feasibility of implementing the study protocol [126–131]. In order to capture other aspects of feasibility and acceptability, we will ask participants to answer several open-ended questions about their involvement with the intervention and study procedures more generally (e.g., Were there challenges to participating in this study for you?). No formal qualitative analyses will be conducted, but we will review participant responses to identify possible areas of improvement to the interventions or study procedures . Safety and adverse events will also be recorded after each intervention session using a yes/no symptom checklist and an open-ended prompt for participants to disclose any other possible adverse effects.
Baseline assessment and secondary outcomes
Consistent with the purpose of pilot RCTs [100, 117], the additional measures reflect baseline, outcome, and possible process variables that we anticipate will be included in a subsequent efficacy trial . Table 2 indicates the schedule for collecting these psychometrically sound measures, and Additional file 1: Appendix 2 includes more detailed descriptions. The baseline assessment will include demographic and pain and health history questions that align with items recommended by the NIH Task Force on Research Standards for cLBP and the Back Pain Consortium (BACPAC) minimum dataset . Moreover, many of the biobehavioral and patient-reported measures of this study were selected to be consistent with BACPAC recommendations to (1) assess meaningful outcomes following an intervention and (2) include phenotyping measures that may predict who responds to an intervention . Although considered secondary outcomes in the current study, the primary clinical pain outcome measures for a future efficacy trial will be pain intensity and pain interference. The NIH PROMIS pain intensity-short form scale  will be used in analyses to determine clinical significance for the proposed study and subsequent efficacy trial by assessing improvements over the last 7 days on average using an 11-point NRS (0 = no pain, 10 = most pain imaginable). Finally, participants will also complete behavioral and physiological assessments at pre- and post-intervention, including physical functioning tasks, quantitative sensory testing, and heart rate variability.
Physical functioning assessments
Two tests will be used to assess physical functioning—the Short Physical Performance Battery (SPPB)  and the Back Performance Scale (BPS) . The SPPB is a widely used measure of physical function and consists of three tasks: usual gait speed over 4 meters, standing balance, and a chair stand test. The BPS will be used to assess both functional performance and movement-evoked pain through five tasks that are considered difficult for people with cLBP [159, 160]. An assessor will rate physical functioning for participants on each task using a 0–3 scale (total score = 0–15 where higher scores represent worse physical functioning). To measure movement-evoked pain, participants are asked to rate their pain immediately after each task on a 101-point visual analogue scale where 0 = no pain and 100 = most intense pain imaginable.
Quantitative Sensory Testing (QST)
We will use QST to determine pain modulatory balance via pressure pain threshold (PPT), temporal summation (TS) of mechanical pain, and conditioned pain modulation (CPM). First, to determine PPT, a handheld pressure algometer with a 1-cm2 tip (Medoc, Ltd., AlgoMed, Ramat Yishai, Israel) will be applied to the participants trapezius muscle at a steadily increasing rate of pressure. The participant will press a button when the pressure sensation first becomes painful. This procedure will be repeated five times on the same trapezius muscle, and the mean pressure rating across the five trials will be used for analyses on remote pain sensitivity. Second, to determine remote and local TS of mechanical pain, we will use a 300 g nylon monofilament (Touchtest Sensory Evaluator 6.65) to deliver a pinprick sensation to the back of the hand (remote) and lumbar spine (local). A single pinprick stimulus will be delivered and the participant will give a verbal pain rating from 0 (no pain) to 100 (most intense pain imaginable). Then, a series of 10 stimuli (once per second) will be delivered to the same location, and the participant will again give a rating of the greatest pain intensity experienced during the 10 stimuli. This procedure will be repeated twice at each site (back of each hand and bilaterally on lumbar spine) and the trials for each site will be averaged. TS will be used as an indicator of pain facilitation and calculated for each site by subtracting the average rating of the single stimulus from the 10 repeated stimuli. Third, to determine CPM, the test stimulus will be PPT at the trapezius, as described above, and the conditioning stimulus will be immersion of the hand (contralateral to the PPT) in cold water for 1 min at 12 °C (ARCTIC A25 refrigerated bath with an SC150 immersion circulator; ThermoFisher Scientific, USA). PPT will be assessed immediately before cold water immersion, 30 s after immersion, and immediately after withdrawing the hand from immersion. CPM will be used as an indicator of pain inhibition and will be calculated by subtracting the PPT before immersion from the PPT during immersion.
Physiological data will be recorded throughout the first and last BAT session and summarized across three epochs: 5-min before BAT (resting baseline), 12 min during BAT (active breathing), and 5 min after the BAT practice (recovery) . A Biopac MP150 system with BioNomadix transmitter and RSPEC-R and Oxy100E modules (MP150-BIOPAC Systems Inc., Goleta, CA, USA) will be used for data acquisition, and Biopac’s Acknowledge software will be used for data recording and analyses. We will use a 3-lead EEG, lead II configuration, to record HRV in both the frequency and time domains. A pulse oximeter on the finger of the participant will be used to measure oxygen saturation. To gather baseline data, participants will be asked to lay still for 5 min while reclined before beginning the intervention. Physiological data acquisition will continue throughout the 12-min BAT intervention, and the last 5 min of silence in each intervention will be considered post-test data. Blood pressure will also be measured while the participant is reclined with three continuous readings immediately before the baseline period and after the 5 min of silence. The following physiological parameters will be summarized for each intervention, separated by baseline, during BAT, and post-BAT: Low-frequency (LF), high-frequency (HF), low-to-high frequency (LF/HF), standard deviation of normal-to-normal intervals (SDNN), root mean square of successive differences between heartbeats (RMSSD), oxygen saturation, and blood pressure. We will attempt to schedule Visit 2 and 3 at the same time of day to provide the best comparison of pre-post physiological measures [161, 162].
We will assess intervention group equivalence on baseline and outcome variables using relevant univariate tests (chi-square and Kruskal-Wallis) with statistical significance set at p < 0.05. Descriptive statistics (percentages, frequencies, means, standard deviations, and 95% confidence intervals) will be used to summarize the results at each timepoint and determine feasibility and acceptability. For feasibility, successful retention is defined as at least 70% of enrolled participants completing the intervention sessions and monthly follow-ups. Acceptability is defined as at least 70% of participants reporting high average ratings (≥ 7 of 10) on acceptability and satisfaction measures. In order to address the secondary objective examining the plausibility of clinical improvement, we will calculate the proportion of participants who report a “moderately important” pain reduction of 30% or greater for each intervention group using the ratings of average pain intensity over the past week. We also plan to explore potential covariates and predictors of treatment response (e.g., age, sex, QST).
This will be the first study to examine the effects of a conscious connected breathing with breath retention intervention for individuals with chronic pain. The successful completion of this early stage study will provide data regarding the feasibility and acceptability to conduct a future RCT testing the efficacy and mechanisms of this breathing self-management practice for adults with cLBP [131, 163]. The study is designed to be consistent with recommendations for conducting pilot RCTs [100, 117, 164, 165] and for intervention development [61, 166, 167]. Specifically, this pilot feasibility study is considered a smaller-scale version of an anticipated RCT where the target population is recruited and participants are randomly assigned to the active intervention or sham control intervention and complete all questionnaires, behavioral assessments, and procedures as planned in a future efficacy trial. Moreover, in accordance with models of intervention development, information gathered from this study will be used to refine the procedures, optimize the interventions, and adjust the elements of study design and implementation prior to proceeding with a larger trial. Given the need for safe, effective, and accessible treatments for chronic pain [5, 12, 16, 168] and the increasing usage of complementary and integrative health approaches , the proposed intervention focused on the power of conscious breathing for pain management has high potential impact as a standalone practice or adjunct to existing treatments [24, 25, 169].
There is currently little research examining the effects of breathing practices in chronic pain populations [23, 24, 170]. Although there is solid theoretical rationale to expect breathing practices and breathwork interventions to be beneficial for individuals suffering with chronic pain [22, 26, 33, 72, 85, 171], high-quality evidence for their efficacy is sparse [23–25]. The relatively few RCTs available reveal that various breathing interventions can improve back pain and pain-related outcomes, but significant heterogeneity in study design, quality, length of follow-ups, and type of breathing interventions limit any strong conclusions [23–25]. Nevertheless, we elected to test this particular conscious connected breathing intervention that also includes breath retention for several reasons. (1) There is empirical evidence supporting that this specific breathing practice influences biological activity relevant to chronic pain, such as decreased inflammation and adaptive immune, nervous, and metabolic activity [47–49, 58]. (2) This breathing technique is relatively easy to learn and quick to practice on one’s own . Therefore, it is advantageous as a remote self-management practice that is expected to be more potent than simply deep breathing and more accessible compared to other emotionally activating breathwork interventions that need to be practiced in a specific setting under the supervision of a trained therapist or facilitator [42–45, 172–175]. (3) Millions of people around the world already engage in this breathing practice on their ownFootnote 2, but comparably little scientific research has tested its safety and efficacy. The proposed study is a precursor to a larger efficacy trial which is intended to help bridge this disconnect between widespread public usage and scientific evidence [5, 61]. (4) Finally, because breathing is free and accessible to everyone and the intervention can be practiced remotely with fidelity through the use of replicable audio, video, or app-based media, it has enormous potential for scalability as a self-management strategy.
The sham control intervention chosen for this early stage study deserves discussion. The purpose of the Standard-BAT condition is to minimize threats to internal validity by controlling for treatment non-specific factors (e.g., attention, expectations) and key treatment specific factors (e.g., breathing instructions, relaxation) [52, 53, 102, 176–179]. Holding most components of the BAT interventions constant addresses the well-known issue of placebo effects in pain research [102–104, 180–183] and enhances internal validity of the study by isolating the putative therapeutic mechanism(s) of the Focused-BAT/CCBR intervention (i.e., connected breathing with retention technique, mindful body awareness, and consciously releasing tension). While we do not expect the Standard-BAT to be completely inert, as demonstrated by previous studies showing a similar sham intervention reduces pain sensitivity and unpleasantness [38, 124], it is expected to be less effective than CCBR, yet equivalent in terms of engagement, credibility, and expectations of benefit. As such, the Standard-BAT is considered a stringent or highly formidable control condition. The use of a high formidability control condition, compared to a low formidability control condition (e.g., waitlist), increases the chances of type II error, or the incorrect inference that there is no difference between the treatment arms when there indeed is [52, 53, 104, 176]. Therefore, some researchers recommend against a highly formidable control group in early stage studies because small treatment effects may lead to prematurely abandoning the development of a promising intervention [52, 184]. Nevertheless, the current study design aligns with the purpose of pilot RCTs in that it will provide feasibility data regarding participants’ satisfaction, expectations, and adherence to the interventions that are anticipated to be used in a larger trial. Moreover, this pilot study will provide valuable data regarding the acceptability and credibility of this control condition. While no control condition is perfect, the Standard-BAT in this study is structurally equivalent to the Focused-BAT with respect to treatment format, implementation, and several other treatment specific and non-specific factors, which will allow for strong causal conclusions regarding treatment effects and mechanisms in future studies [102–104].
Although there are several strengths to the proposed study, such as the multimethod assessments, standardized interventions, and a randomized controlled design, there are limitations to highlight. Considering this pilot RCT is a smaller version of a future efficacy trial, the current “dose” of a 5-day CCBR practice may be insufficient for clinically meaningful changes in the proposed primary efficacy outcomes of pain intensity and pain interference. It may be that this self-management practice needs to be maintained over a longer period of time for substantial or sustained benefits. For example, clinical trials of breathing exercises typically involve daily practice for at least 4 weeks and often up to 8 or 12 weeks [24, 25, 185]. Moreover, while we can visually monitor treatment fidelity during the in-person BAT sessions, we will be unable to determine fidelity when participants practice the interventions at-home. Additionally, there may be unknown safety issues with the CCBR intervention (e.g., cyclic hyperventilation, breath holding, mindful body awareness) that are over- or under-represented in the small sample size of the current study. We will monitor adverse events by soliciting expected and unexpected side-effects of the intervention, but, ultimately, a larger study is needed to establish the safety of the intervention. Finally, we caution overinterpretation of the results regarding the plausibility of improvement in pain-related outcomes. These analyses are considered exploratory to discern whether the intervention has any effects at all by providing initial evidence that the target of clinical significance (≥ 30% improvement in pain intensity), rather than statistical significance, is achievable for some people [100, 105, 106, 132]. If the ratio of participants showing meaningful improvement favors the control, we may need to modify the sham control intervention or consider a three-arm trial design for the larger follow-up trial .
In conclusion, this study is the first step to advance a line of research testing whether this novel, innovative intervention is safe and effective as a self-management practice for those with cLBP. The proposed intervention empowers people to care for themselves by taking advantage of their breathing and attention to self-regulate their body and mind. Subsequent efficacy testing of this breathing practice, if feasible, has high potential to advance our understanding of pain mechanisms and identify a promising new self-management intervention for chronic pain.
Availability of data and materials
When the study is completed, de-identified data will be made available from the corresponding author on reasonable request.
The connected breathing with breath retention intervention is commonly known as the Wim Hof Method or Wim Hof Breathing because it was popularized by a man named Wim Hof. Much of the early research on this intervention include either Wim Hof as a case study or participants who were personally trained by him.
As of 1/14/2022, there are over 39 million views on the top Wim Hof Breathing video on Youtube (“Guided Wim Hof Breathing Method”) and many other similar guided breathing videos have several million views.
Chronic low back pain
Conscious connected breathing with breath retention
Heart rate variability
Randomized controlled trial
Breathing and Attention Training
University of Florida
Hartvigsen J, Hancock MJ, Kongsted A, Louw Q, Ferreira ML, Genevay S, et al. What low back pain is and why we need to pay attention. Lancet. 2018;391(10137):2356–67.
Vos T, Abajobir AA, Abate KH, Abbafati C, Abbas KM, Abd-Allah F, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1211–59.
Buchbinder R, van Tulder M, Öberg B, Costa LM, Woolf A, Schoene M, et al. Low back pain: a call for action. Lancet. 2018;391(10137):2384–8.
Da Silva T, Mills K, Brown BT, Herbert RD, Maher CG, Hancock MJ. Risk of recurrence of low back pain: a systematic review. J Orthop Sports Phys Ther. 2017;47(5):305–13.
Foster NE, Anema JR, Cherkin D, Chou R, Cohen SP, Gross DP, et al. Prevention and treatment of low back pain: evidence, challenges, and promising directions. Lancet. 2018;391(10137):2368–83.
Qaseem A, Wilt TJ, McLean RM, Forciea MA. Clinical Guidelines Committee of the American College of P, Denberg TD, et al. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017;166(7):514–30.
George SZ, Goertz C, Hastings SN, Fritz JM. Transforming low back pain care delivery in the United States. Pain. 2020;161(12):2667–73.
Hush JM. Low back pain: it is time to embrace complexity. Pain. 2020;161(10):2248–51.
Croft P, Louw Q, Briggs AM. Transforming back pain care-why, what, and how? Pain. 2020;161(12):2657–8.
Borsook D, Youssef AM, Simons L, Elman I, Eccleston C. When pain gets stuck: the evolution of pain chronification and treatment resistance. Pain. 2018;159(12):2421–36.
Eccleston C, Blyth FM, Dear BF, Fisher EA, Keefe FJ, Lynch ME, et al. Managing patients with chronic pain during the COVID-19 outbreak: considerations for the rapid introduction of remotely supported (eHealth) pain management services. Pain. 2020;161(5):889–93.
Oliveira VC, Ferreira PH, Maher CG, Pinto RZ, Refshauge KM, Ferreira ML. Effectiveness of self-management of low back pain: systematic review with meta-analysis. Arthritis Care Res (Hoboken). 2012;64(11):1739–48.
Chen L, Michalsen A. Management of chronic pain using complementary and integrative medicine. BMJ. 2017;357:j1284.
Lee C, Crawford C, Hickey A. Mind–body therapies for the self-management of chronic pain symptoms. Pain Med. 2014;15(S1):S21–39.
Becker WC, DeBar LL, Heapy AA, Higgins D, Krein SL, Lisi A, et al. A Research Agenda for Advancing Non-pharmacological Management of Chronic Musculoskeletal Pain: Findings from a VHA State-of-the-art Conference. J Gen Intern Med. 2018;33(Suppl 1):11–5.
Cherkin DC, Deyo RA, Goldberg H. Time to Align Coverage with Evidence for Treatment of Back Pain. J Gen Intern Med. 2019;34(9):1910–2.
Elbers S, Wittink H, Pool JJM, Smeets R. The effectiveness of generic self-management interventions for patients with chronic musculoskeletal pain on physical function, self-efficacy, pain intensity and physical activity: a systematic review and meta-analysis. Eur J Pain. 2018;22(9):1577–96.
Barlow J, Wright C, Sheasby J, Turner A, Hainsworth J. Self-management approaches for people with chronic conditions: a review. Patient Educ Couns. 2002;48(2):177–87.
Diener I. Self-Management and Low Back Pain. In: Self-Management in Chronic Illness; 2021. p. 75–95.
Becker WC, Dorflinger L, Edmond SN, Islam L, Heapy AA, Fraenkel L. Barriers and facilitators to use of non-pharmacological treatments in chronic pain. BMC Fam Pract. 2017;18(1):41.
Smith SM, Gewandter JS, Kitt RA, Markman JD, Vaughan JA, Cowan P, et al. Participant preferences for pharmacologic chronic pain treatment trial characteristics: an ACTTION adaptive choice-based conjoint study. J Pain. 2016;17(11):1198–206.
Jafari H, Courtois I, Van den Bergh O, Vlaeyen JWS, Van Diest I. Pain and respiration: a systematic review. Pain. 2017;158(6):995–1006.
Anderson BE, Bliven KCH. The use of breathing exercises in the treatment of chronic, nonspecific low back pain. J Sport Rehabil. 2017;26(5):452–8.
Sielski R, Rief W, Glombiewski JA. Efficacy of biofeedback in chronic back pain: a meta-analysis. Int J Behav Med. 2017;24(1):25–41.
Usman A, Tanwar T, Veqar Z. Exploring the role of respiratory intervention as an effective adjunct tool in the management of chronic low back pain: a scoping systematic review. J Bodyw Mov Ther. 2022;33:60–68.
Paccione CE, Jacobsen HB. Motivational non-directive resonance breathing as a treatment for chronic widespread pain. Front Psychol. 2019;10:1207.
Busch V, Magerl W, Kern U, Haas J, Hajak G, Eichhammer P. The effect of deep and slow breathing on pain perception, autonomic activity, and mood processing—an experimental study. Pain Med. 2012;13(2):215–28.
Zautra AJ, Fasman R, Davis MC, Craig AD. The effects of slow breathing on affective responses to pain stimuli: an experimental study. Pain. 2010;149(1):12–8.
Courtois I, Gholamrezaei A, Jafari H, Lautenbacher S, Van Diest I, Van Oudenhove L, et al. Respiratory Hypoalgesia? The Effect of Slow Deep Breathing on Electrocutaneous, Thermal, and Mechanical Pain. J Pain. 2020;21(5-6):616–32.
Jafari H, Gholamrezaei A, Franssen M, Van Oudenhove L, Aziz Q, Van den Bergh O, et al. Can slow deep breathing reduce pain? An experimental study exploring mechanisms. J Pain. 2020;21(9-10):1018–30.
Martin SL, Kerr KL, Bartley EJ, Kuhn BL, Palit S, Terry EL, et al. Respiration-induced hypoalgesia: exploration of potential mechanisms. J Pain. 2012;13(8):755–63.
Lehrer PM, Gevirtz R. Heart rate variability biofeedback: how and why does it work? Front Psychol. 2014;5:756.
Gerritsen RJS, Band GPH. Breath of life: the respiratory vagal stimulation model of contemplative activity. Front Hum Neurosci. 2018;12:397.
Noble DJ, Hochman S. Hypothesis: pulmonary afferent activity patterns during slow, deep breathing contribute to the neural induction of physiological relaxation. Front Psychol. 2019;10:1176.
Zaccaro A, Piarulli A, Laurino M, Garbella E, Menicucci D, Neri B, et al. How breath-control can change your life: a systematic review on psycho-physiological correlates of slow breathing. Front Hum Neurosci. 2018;12:353.
Jerath R, Edry JW, Barnes VA, Jerath V. Physiology of long pranayamic breathing: neural respiratory elements may provide a mechanism that explains how slow deep breathing shifts the autonomic nervous system. Med Hypotheses. 2006;67(3):566–71.
Fonkoue IT, Marvar PJ, Norrholm SD, Kankam ML, Li Y, DaCosta D, et al. Acute effects of device-guided slow breathing on sympathetic nerve activity and baroreflex sensitivity in posttraumatic stress disorder. Am J Physiol Heart Circ Physiol. 2018;315(1):H141–H9.
Wells RE, Collier J, Posey G, Morgan A, Auman T, Strittmatter B, et al. Attention to breath sensations does not engage endogenous opioids to reduce pain. Pain. 2020;161(8):1884–93.
Hilton L, Hempel S, Ewing BA, Apaydin E, Xenakis L, Newberry S, et al. Mindfulness meditation for chronic pain: systematic review and meta-analysis. Ann Behav Med. 2017;51(2):199–213.
Grof S, Grof C. Holotropic breathwork. Albany: State University of New York; 2010.
Uthaug MV, Mason NL, Havenith MN, Vancura M, Ramaekers JG. An experience with Holotropic Breathwork is associated with improvement in non-judgement and satisfaction with life while reducing symptoms of stress in a Czech-speaking population. J Psychedelic Stud. 2021;5(3):176–89.
Manne J. Conscious breathing: how shamanic breathwork can transform your life: North Atlantic Books; 2004.
Tonkov G. Feel to heal: Releasing trauma through body awareness and breathwork practice. Brooklyn: BioDynamic Breathwork & Trauma Release Institute; 2019.
Taylor K. Holotropic breathwork: A new approach to self-exploration and therapy. J Transpers Psychol. 2011;43(1):108.
de Wita PA, Menezesb CB, Dias-de-Oliveirac CA, da Luz Costad RV, Cruze RM. Rebirthing-Breathwork, activation of the autonomic nervous system, and psychophysiological defenses. Revista Brasileira de Psicoterapia. 2018;20(2):29–42.
Langevin HM. Moving the complementary and integrative health research field toward whole person health. J Altern Complement Med. 2021;27(8):623–6.
Buijze GA, De Jong HMY, Kox M, van de Sande MG, Van Schaardenburg D, Van Vugt RM, et al. An add-on training program involving breathing exercises, cold exposure, and meditation attenuates inflammation and disease activity in axial spondyloarthritis - A proof of concept trial. PLoS ONE. 2019;14(12):e0225749.
Kox M, van Eijk LT, Zwaag J, van den Wildenberg J, Sweep FC, van der Hoeven JG, et al. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans. Proc Natl Acad Sci U S A. 2014;111(20):7379–84.
Zwaag J, Ter Horst R, Blazenovic I, Stoessel D, Ratter J, Worseck JM, et al. Involvement of Lactate and Pyruvate in the Anti-Inflammatory Effects Exerted by Voluntary Activation of the Sympathetic Nervous System. Metabolites. 2020;10(4):148.
Kox M, Stoffels M, Smeekens SP, Van Alfen N, Gomes M, Eijsvogels TM, et al. The influence of concentration/meditation on autonomic nervous system activity and the innate immune response: a case study. Psychosom Med. 2012;74(5):489–94.
van Middendorp H, Kox M, Pickkers P, Evers AW. The role of outcome expectancies for a training program consisting of meditation, breathing exercises, and cold exposure on the response to endotoxin administration: a proof-of-principle study. Clin Rheumatol. 2016;35(4):1081–5.
Gold SM, Enck P, Hasselmann H, Friede T, Hegerl U, Mohr DC, et al. Control conditions for randomised trials of behavioural interventions in psychiatry: a decision framework. Lancet Psychiatry. 2017;4(9):725–32.
Mohr DC, Spring B, Freedland KE, Beckner V, Arean P, Hollon SD, et al. The selection and design of control conditions for randomized controlled trials of psychological interventions. Psychother Psychosom. 2009;78(5):275–84.
Enck P, Zipfel S. Placebo effects in psychotherapy: a framework. Front Psychiatry. 2019;10:456.
Aday JS, Heifets BD, Pratscher SD, Bradley E, Rosen R, Woolley JD. Great Expectations: recommendations for improving the methodological rigor of psychedelic clinical trials. Psychopharmacology. 2022;239(6):1989–2010.
Zwaag J, Naaktgeboren R, van Herwaarden AE, Pickkers P, Kox M. The effects of cold exposure training and a breathing exercise on the inflammatory response in humans: A pilot study. Psychosom Med. 2022;84(4):457.
Kopplin CS, Rosenthal L. The positive effects of combined breathing techniques and cold exposure on perceived stress: a randomised trial. Curr Psychol. 2022:1–13.
Brussee P, Zwaag J, van Eijk L, van der Hoeven JG, Moviat MA, Pickkers P, et al. Stewart analysis unmasks acidifying and alkalizing effects of ionic shifts during acute severe respiratory alkalosis. J Crit Care. 2021;66:1–5.
Djarova T, Ilkov A, Varbanova A, Nikiforova A, Mateev G. Human growth hormone, cortisol, and acid-base balance changes after hyperventilation and breath-holding. Int J Sports Med. 1986;7(06):311–5.
Citherlet T, Crettaz von Roten F, Kayser B, Guex K. Acute effects of the wim hof breathing method on repeated sprint ability: a pilot study. Front Sports Act Living. 2021;3:700757.
Onken LS, Carroll KM, Shoham V, Cuthbert BN, Riddle M. Reenvisioning clinical science: Unifying the discipline to improve the public health. Clin Psychol Sci. 2014;2(1):22–34.
Czajkowski SM, Powell LH, Adler N, Naar-King S, Reynolds KD, Hunter CM, et al. From ideas to efficacy: The ORBIT model for developing behavioral treatments for chronic diseases. Health Psychol. 2015;34(10):971.
Tracy LM, Ioannou L, Baker KS, Gibson SJ, Georgiou-Karistianis N, Giummarra MJ. Meta-analytic evidence for decreased heart rate variability in chronic pain implicating parasympathetic nervous system dysregulation. Pain. 2016;157(1):7–29.
Bruehl S, Olsen RB, Tronstad C, Sevre K, Burns JW, Schirmer H, et al. Chronic pain-related changes in cardiovascular regulation and impact on comorbid hypertension in a general population: the Tromso study. Pain. 2018;159(1):119–27.
Davydov DM. Cardiac vagal tone as a reliable index of pain chronicity and severity. Pain. 2017;158(12):2496–7.
Davydov DM, Naliboff B, Shahabi L, Shapiro D. Asymmetries in reciprocal barorefex mechanisms and chronic pain severity: Focusing on irritable bowel syndrome. Neurogastroenterol. Motil. 2018;30:e13186.
Reyes del Paso GA, Ladron M, de Guevara C, Montoro CI. Breath-holding during exhalation as a simple manipulation to reduce pain perception. Pain Med. 2015;16(9):1835–41.
Bruehl S, Chung OY. Interactions between the cardiovascular and pain regulatory systems: an updated review of mechanisms and possible alterations in chronic pain. Neurosci Biobehav Rev. 2004;28(4):395–414.
Liang CZ, Li H, Tao YQ, Zhou XP, Yang ZR, Li FC, et al. The relationship between low pH in intervertebral discs and low back pain: a systematic review. Arch Med Sci. 2012;8(6):952–6.
Quade BN, Parker MD, Occhipinti R. The therapeutic importance of acid-base balance. Biochem Pharmacol. 2021;183:114278.
Krapf R, Beeler I, Hertner D, Hulter HN. Chronic respiratory alkalosis: the effect of sustained hyperventilation on renal regulation of acid–base equilibrium. New England J Med. 1991;324(20):1394–401.
Maric V, Ramanathan D, Mishra J. Respiratory regulation & interactions with neuro-cognitive circuitry. Neurosci Biobehav Rev. 2020;112:95–106.
Muzik O, Reilly KT, Diwadkar VA. "Brain over body"-a study on the willful regulation of autonomic function during cold exposure. Neuroimage. 2018;172:632–41.
Faull OK, Subramanian HH, Ezra M, Pattinson KTS. The midbrain periaqueductal gray as an integrative and interoceptive neural structure for breathing. Neurosci Biobehav Rev. 2019;98:135–44.
Marlow LL, Faull OK, Finnegan SL, Pattinson KTS. Breathlessness and the brain: the role of expectation. Curr Opin Support Palliat Care. 2019;13(3):200–10.
Yu R, Gollub RL, Spaeth R, Napadow V, Wasan A, Kong J. Disrupted functional connectivity of the periaqueductal gray in chronic low back pain. Neuroimage Clin. 2014;6:100–8.
Marchand F, Perretti M, McMahon SB. Role of the immune system in chronic pain. Nat Rev Neurosci. 2005;6(7):521–32.
Sibille KT, Steingrímsdóttir ÓA, Fillingim RB, Stubhaug A, Schirmer H, Chen H, et al. Investigating the burden of chronic pain: an inflammatory and metabolic composite. Pain Res Manag. 2016;2016:7657329.
Epel ES. The geroscience agenda: Toxic stress, hormetic stress, and the rate of aging. Ageing Res Rev. 2020;63:101167.
Mattson MP. Hormesis defined. Ageing Res Rev. 2008;7(1):1–7.
Agathokleous E, Calabrese EJ. Hormesis: the dose response for the 21st century: The future has arrived. Toxicology. 2019;425:152249.
Oliveira MF, Geihs MA, França TF, Moreira DC, Hermes-Lima M. Is “preparation for oxidative stress” a case of physiological conditioning hormesis? Front physiol. 2018;9:945.
Giraud-Billoud M, Rivera-Ingraham GA, Moreira DC, Burmester T, Castro-Vazquez A, Carvajalino-Fernández JM, et al. Twenty years of the ‘Preparation for Oxidative Stress’(POS) theory: Ecophysiological advantages and molecular strategies. Comp Biochem Physiol A Mol Integr Physiol. 2019;234:36–49.
Joyner MJ, Baker SE. Take a deep, resisted, breath. Am Heart Assoc. 2021;10:e022203.
Weng HY, Feldman JL, Leggio L, Napadow V, Park J, Price CJ. Interventions and Manipulations of Interoception. Trends Neurosci. 2021;44(1):52–62.
Strigo IA, Craig AD. Interoception, homeostatic emotions and sympathovagal balance. Philos Trans R Soc Lond B Biol Sci. 2016;371(1708):20160010.
Farb N, Daubenmier J, Price CJ, Gard T, Kerr C, Dunn BD, et al. Interoception, contemplative practice, and health. Front Psychol. 2015;6:763.
Khalsa SS, Adolphs R, Cameron OG, Critchley HD, Davenport PW, Feinstein JS, et al. Interoception and mental health: a roadmap. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3(6):501–13.
Price C, Mehling W. Body awareness and pain. In: Integrative pain management. Williston: Handspring publishing; 2016. p. 235–51.
Dale EA, Ben Mabrouk F, Mitchell GS. Unexpected benefits of intermittent hypoxia: enhanced respiratory and nonrespiratory motor function. Physiol (Bethesda). 2014;29(1):39–48.
Fuller DD, Mitchell GS. Respiratory neuroplasticity - Overview, significance and future directions. Exp Neurol. 2017;287(Pt 2):144–52.
Vose AK, Welch JF, Nair J, Dale EA, Fox EJ, Muir GD, et al. Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease. Exp Neurol. 2022;347:113891.
McEwen BS. Allostasis and the epigenetics of brain and body health over the life course: the brain on stress. JAMA Psychiatry. 2017;74(6):551–2.
Pratscher S, Mickle AM, Marks JG, Rocha H, Bartsch F, Schmidt J, et al. Optimizing chronic pain treatment with enhanced neuroplastic responsiveness: a pilot randomized controlled trial. Nutrients. 2021;13(5):1556.
Sibille KT, Bartsch F, Reddy D, Fillingim RB, Keil A. Increasing neuroplasticity to bolster chronic pain treatment: a role for intermittent fasting and glucose administration? J Pain. 2016;17(3):275–81.
Price CJ, Hooven C. Interoceptive Awareness Skills for Emotion Regulation: Theory and Approach of Mindful Awareness in Body-Oriented Therapy (MABT). Front Psychol. 2018;9:798.
Schindler EA, D’Souza DC. The therapeutic potential of psychedelics. Science. 2022;378(6624):1051–3.
Eldridge SM, Lancaster GA, Campbell MJ, Thabane L, Hopewell S, Coleman CL, et al. Defining feasibility and pilot studies in preparation for randomised controlled trials: development of a conceptual framework. PLoS ONE. 2016;11(3):e0150205.
Morgan B, Hejdenberg J, Kuleszewicz K, Armstrong D, Ziebland S. Are some feasibility studies more feasible than others? A review of the outcomes of feasibility studies on the ISRCTN registry. Pilot Feasibility Stud. 2021;7(1):195.
Freedland KE. Pilot trials in health-related behavioral intervention research: Problems, solutions, and recommendations. Health Psychol. 2020;39(10):851–62.
Thabane L, Lancaster G. A guide to the reporting of protocols of pilot and feasibility trials. Pilot and Feasibility Studies. 2019;5(1):37.
Hohenschurz-Schmidt D, Draper-Rodi J, Vase L, Scott W, McGregor A, Soliman N, et al. Blinding and sham control methods in trials of physical, psychological, and self-management interventions for pain (article I): a systematic review and description of methods. Pain. 2022;10:1097.
Baskin TW, Tierney SC, Minami T, Wampold BE. Establishing specificity in psychotherapy: a meta-analysis of structural equivalence of placebo controls. J Consult Clin Psychol. 2003;71(6):973.
Hohenschurz-Schmidt D, Draper-Rodi J, Vase L, Scott W, McGregor A, Soliman N, et al. Blinding and sham control methods in trials of physical, psychological, and self-management interventions for pain (article II): a meta-analysis relating methods to trial results. Pain. 2022.
Powell LH, Kaufmann PG, Freedland KE. Clinical significance. In: Behavioral Clinical Trials for Chronic Diseases: Springer; 2021. p. 97–124.
Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9(2):105–21.
Smith SM, Dworkin RH, Turk DC, McDermott MP, Eccleston C, Farrar JT, et al. Interpretation of chronic pain clinical trial outcomes: IMMPACT recommended considerations. Pain. 2020;161(11):2446–61.
Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001;94(2):149–58.
Dworkin RH, Turk DC, McDermott MP, Peirce-Sandner S, Burke LB, Cowan P, et al. Interpreting the clinical importance of group differences in chronic pain clinical trials: IMMPACT recommendations. Pain. 2009;146(3):238–44.
Dworkin RH, Evans SR, Mbowe O, McDermott MP. Essential statistical principles of clinical trials of pain treatments. Pain Rep. 2021;6(1):e863.
Dworkin RH, Anderson BT, Andrews N, Edwards RR, Grob CS, Ross S, et al. If the doors of perception were cleansed, would chronic pain be relieved? Evaluating the benefits and risks of psychedelics. J Pain. 2022;23(10):1666–79.
Kraemer HC, Mintz J, Noda A, Tinklenberg J, Yesavage JA. Caution regarding the use of pilot studies to guide power calculations for study proposals. Arch Gen Psychiatry. 2006;63(5):484–9.
Tang Y-Y, Ma Y, Fan Y, Feng H, Wang J, Feng S, et al. Central and autonomic nervous system interaction is altered by short-term meditation. Proc Natl Acad Sci U S A. 2009;106(22):8865–70.
Mehling WE, DiBlasi Z, Hecht F. Bias control in trials of bodywork: a review of methodological issues. J Altern Complement Med. 2005;11(2):333–42.
Gewandter JS, Eisenach JC, Gross RA, Jensen MP, Keefe FJ, Lee DA, et al. Checklist for the preparation and review of pain clinical trial publications: a pain-specific supplement to CONSORT. Pain Rep. 2019;4(3):e621.
Schulz KF, Altman DG, Moher D, The CG. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. Trials. 2010;11(1):32.
Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016;355:i5239.
Nicholas M, Vlaeyen JW, Rief W, Barke A, Aziz Q, Benoliel R, et al. The IASP classification of chronic pain for ICD-11: chronic primary pain. Pain. 2019;160(1):28–37.
Deyo RA, Dworkin SF, Amtmann D, Andersson G, Borenstein D, Carragee E, et al. Report of the NIH Task Force on research standards for chronic low back pain. J Pain. 2014;15(6):569–85.
Howick J, Webster RK, Rees JL, Turner R, Macdonald H, Price A, et al. TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls. PLoS Med. 2020;17(9):e1003294.
Evans K, Colloca L, Pecina M, Katz N. What can be done to control the placebo response in clinical trials? A narrative review. Contemp Clin Trials. 2021;107:106503.
Fillingim RB, Woods AJ, Ahn H, Wu SS, Redden DT, Lai S, et al. Pain relief for osteoarthritis through combined treatment (PROACT): Protocol for a randomized controlled trial of mindfulness meditation combined with transcranial direct current stimulation in non-Hispanic black and white adults with knee osteoarthritis. Contemp Clin Trials. 2020;98:106159.
Zeidan F, Adler-Neal AL, Wells RE, Stagnaro E, May LM, Eisenach JC, et al. Mindfulness-meditation-based pain relief is not mediated by endogenous opioids. J Neurosci. 2016;36(11):3391–7.
Zeidan F, Emerson NM, Farris SR, Ray JN, Jung Y, McHaffie JG, et al. Mindfulness meditation-based pain relief employs different neural mechanisms than placebo and sham mindfulness meditation-induced analgesia. J Neurosci. 2015;35(46):15307–25.
Tabor A, Bateman S, Scheme EJ, schraefel mc. Comparing heart rate variability biofeedback and simple paced breathing to inform the design of guided breathing technologies. Front Comput Sci. 2022;4:151.
Darnall BD, Sturgeon JA, Kao MC, Hah JM, Mackey SC. From Catastrophizing to Recovery: a pilot study of a single-session treatment for pain catastrophizing. J Pain Res. 2014;7:219–26.
Lysne PE, Palit S, Morais CA, DeMonte LC, Lakdawala M, Sibille KT, et al. Adaptability and Resilience in Aging Adults (ARIAA): protocol for a pilot and feasibility study in chronic low back pain. Pilot Feasibility Stud. 2021;7(1):188.
Greenberg J, Popok PJ, Lin A, Kulich RJ, James P, Macklin EA, et al. A mind-body physical activity program for chronic pain with or without a digital monitoring device: proof-of-concept feasibility randomized controlled trial. JMIR Form Res. 2020;4(6):e18703.
Sherman KJ, Wellman RD, Hawkes RJ, Phelan EA, Lee T, Turner JA. T’ai Chi for chronic low back pain in older adults: a feasibility trial. J Altern Complement Med. 2020;26(3):176–89.
Salwen-Deremer JK, Smith MT, Aschbrenner KA, Haskell HG, Speed BC, Siegel CA. A pilot feasibility trial of cognitive-behavioural therapy for insomnia in people with inflammatory bowel disease. BMJ Open Gastroenterol. 2021;8(1):e000805.
Aschbrenner KA, Kruse G, Gallo JJ, Plano Clark VL. Applying mixed methods to pilot feasibility studies to inform intervention trials. Pilot Feasibility stud. 2022;8(1):1–13.
Patel KV, Amtmann D, Jensen MP, Smith SM, Veasley C, Turk DC. Clinical outcome assessment in clinical trials of chronic pain treatments. Pain Rep. 2021;6(1):e784.
Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S, et al. The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005–2008. J Clin Epidemiol. 2010;63(11):1179–94.
Slavich GM, Shields GS. Assessing lifetime stress exposure using the stress and adversity inventory for adults (Adult STRAIN): an overview and initial validation. Psychosom Med. 2018;80(1):17–27.
Younger J, Gandhi V, Hubbard E, Mackey S. Development of the Stanford Expectations of Treatment Scale (SETS): a tool for measuring patient outcome expectancy in clinical trials. Clin Trials. 2012;9(6):767–76.
Cella D, Yount S, Rothrock N, Gershon R, Cook K, Reeve B, et al. The Patient-Reported Outcomes Measurement Information System (PROMIS): progress of an NIH Roadmap cooperative group during its first two years. Med Care. 2007;45(5 Suppl 1):S3.
Amtmann D, Cook KF, Jensen MP, Chen W-H, Choi S, Revicki D, et al. Development of a PROMIS item bank to measure pain interference. Pain. 2010;150(1):173–82.
Yu L, Buysse DJ, Germain A, Moul DE, Stover A, Dodds NE, et al. Development of short forms from the PROMIS™ sleep disturbance and sleep-related impairment item banks. Behav Sleep Med. 2012;10(1):6–24.
Cleeland C, Ryan K. Pain assessment: global use of the Brief Pain Inventory. In: Annals, academy of medicine, Singapore; 1994.
Tan G, Jensen MP, Thornby JI, Shanti BF. Validation of the Brief Pain Inventory for chronic nonmalignant pain. J Pain. 2004;5(2):133–7.
Brummett CM, Bakshi RR, Goesling J, Leung D, Moser SE, Zollars JW, et al. Preliminary validation of the Michigan Body Map. Pain. 2016;157(6):1205–12.
Hassett AL, Pierce J, Goesling J, Fritsch L, Bakshi RR, Kohns DJ, et al. Initial validation of the electronic form of the Michigan Body Map. Reg Anesth Pain Med. 2019.
Ferguson L, Scheman J. Patient global impression of change scores within the context of a chronic pain rehabilitation program. J Pain. 2009;45:145–50.
Scott W, McCracken LM. Patients' impression of change following treatment for chronic pain: global, specific, a single dimension, or many? J Pain. 2015;16(6):518–26.
Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005;113(1-2):9–19.
Fairbank JC, Pynsent PB. The Oswestry disability index. Spine. 2000;25(22):2940–53.
Sullivan MJ, Bishop SR, Pivik J. The pain catastrophizing scale: development and validation. Psychol Assessment. 1995;7(4):524.
Nicholas MK. The pain self-efficacy questionnaire: taking pain into account. Eur J Pain. 2007;11(2):153–63.
Cohen S, Kamarck T, Mermelstein R. Perceived stress scale. Measuring stress: A guide for health and social scientists. 1994;10(2):1–2.
Skapinakis P. The 2-item Generalized Anxiety Disorder scale had high sensitivity and specificity for detecting GAD in primary care; 2007.
Mehling WE, Acree M, Stewart A, Silas J, Jones A. The Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2). PLoS ONE. 2018;13(12):e0208034.
Rolffs JL, Rogge RD, Wilson KG. Disentangling components of flexibility via the hexaflex model: development and validation of the Multidimensional Psychological Flexibility Inventory (MPFI). Assessment. 2018;25(4):458–82.
Sundström FT, Lavefjord A, Buhrman M, McCracken LM. Assessing Psychological Flexibility and Inflexibility in Chronic Pain Using the Multidimensional Psychological Flexibility Inventory (MPFI). J Pain. 2022.
Strand LI, Moe-Nilssen R, Ljunggren AE. Back Performance Scale for the assessment of mobility-related activities in people with back pain. Phys Ther. 2002;82(12):1213–23.
Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994;49(2):M85–94.
Yarnitsky D, Granot M, Granovsky Y. Pain modulation profile and pain therapy: between pro-and antinociception. Pain. 2014;155(4):663–5.
Simon CB, Lentz TA, Orr L, Bishop MD, Fillingim RB, Riley JL III, et al. Static and dynamic pain sensitivity in adults with persistent low back pain: comparison to healthy controls and associations with movement-evoked pain versus traditional clinical pain measures. Clin J Pain. 2021;37(7):494.
Greco CM, Wasan AD, Schneider MJ, Mehling W, Williams DA, Darwin J, et al. Biobehavioral assessments in BACPAC: recommendations, rationale, and methods. Pain Med. 2022.
Magnussen L, Strand LI, Lygren H. Reliability and validity of the back performance scale: observing activity limitation in patients with back pain. Spine. 2004;29(8):903–7.
Palit S, Fillingim RB, Bartley EJ. Pain resilience moderates the influence of negative pain beliefs on movement-evoked pain in older adults. J Behav Med. 2020;43(5):754–63.
Laborde S, Mosley E, Mertgen A. Vagal Tank Theory: The Three Rs of Cardiac Vagal Control Functioning - Resting, Reactivity, and Recovery. Front Neurosci. 2018;12:458.
Laborde S, Hosang T, Mosley E, Dosseville F. Influence of a 30-day slow-paced breathing intervention compared to social media use on subjective sleep quality and cardiac vagal activity. J Clin Med. 2019;8(2):193.
Beets MW, von Klinggraeff L, Weaver RG, Armstrong B, Burkart S. Small studies, big decisions: the role of pilot/feasibility studies in incremental science and premature scale-up of behavioral interventions. Pilot Feasibility Stud. 2021;7(1):173.
Danesh V, Zuniga JA, Timmerman GM, Radhakrishnan K, Cuevas HE, Young CC, et al. Lessons learned from eight teams: The value of pilot and feasibility studies in self-management science. Appl Nurs Res. 2021;57:151345.
National Center for Complementary and Integrative Health. Pilot Studies: Common Uses and Misuses 2017 [Available from: https://www.nccih.nih.gov/grants/pilot-studies-common-uses-and-misuses.
Nielsen L, Riddle M, King JW, Aklin WM, Chen W, Clark D, et al. The NIH Science of Behavior Change Program: Transforming the science through a focus on mechanisms of change. Behav Res Ther. 2018;101:3–11.
Davidson KW, Mogavero JN, Rothman AJ. Using early phase studies to advance intervention research: The science of behavior change. Health Psychol. 2020;39(9):731.
Deyo RA, Mirza SK, Turner JA, Martin BI. Overtreating chronic back pain: time to back off? J Am Board Fam Med. 2009;22(1):62–8.
Siepmann T, Ohle P, Sedghi A, Simon E, Arndt M, Pallesen LP, et al. Randomized sham-controlled pilot study of neurocardiac function in patients with acute ischaemic stroke undergoing heart rate variability biofeedback. Front Neurol. 2021;12:669843. https://doi.org/10.3389/fneur.2021.669843.
Mehling WE, Hamel KA, Acree M, Byl N, Hecht FM. Randomized, controlled trial of breath therapy for patients with chronic low-back pain. Altern Ther Health Med. 2005;11(4):44–52.
Lavretsky H, Feldman Ph DJ. Precision medicine for breath-focused mind-body therapies for stress and anxiety: are we ready yet? Glob Adv Health Med. 2021;10:2164956120986129.
Brewerton TD, Eyerman JE, Cappetta P, Mithoefer MC. Long-term abstinence following holotropic breathwork as adjunctive treatment of substance use disorders and related psychiatric comorbidity. Int J Ment Health Addict. 2011;10(3):453–9.
Eyerman J. A clinical report of Holotropic Breathwork in 11,000 psychiatric inpatients in a community hospital setting. Multidisciplinary Association for Psychedelic Studies Bulletin Special Edition. 2013;23(1):24–7.
de Wita PA, Dias-de-Oliveiraa CA, da Luz Costaa RV, Cruza RM, Menezesa CB. An exploration of the processing of suppressed memories during Rebirthing-Breathwork. Braz J Psychother. 2019;21(1).
Aideyan B, Martin GC, Beeson ET. A practitioner's guide to breathwork in clinical mental health counseling. J. Ment. Health Couns. 2020;42(1):78–94.
Freedland KE, King AC, Ambrosius WT, Mayo-Wilson E, Mohr DC, Czajkowski SM, et al. The selection of comparators for randomized controlled trials of health-related behavioral interventions: recommendations of an NIH expert panel. J Clin Epidemiol. 2019;110:74–81.
Rosenkranz MA, Dunne JD, Davidson RJ. The next generation of mindfulness-based intervention research: what have we learned and where are we headed? Curr Opin Psychol. 2019;28:179–83.
Edmond SN, Turk DC, Williams DA, Kerns RD. Considerations of trial design and conduct in behavioral interventions for the management of chronic pain in adults. Pain Rep. 2019;4(3):e655.
Sherman KJ. The Trials and Tribulations of Selecting Comparison Groups in Randomized Trials of Nonpharmacological Complementary and Integrative Health Interventions. J Altern Complement Med. 2020;26(6):449–55.
Bingel U. Placebo 2.0: the impact of expectations on analgesic treatment outcome. Pain. 2020;161(Suppl 1):S48–56.
Campbell CM, Gilron I, Doshi T, Raja S. Designing and conducting proof-of-concept chronic pain analgesic clinical trials. Pain Rep. 2019;4(3):e697.
Fillingim RB, Price DD. What is controlled for in placebo-controlled trials? Mayo Clin Proc. 2005;80(9):1119–21.
Sanders AE, Slade GD, Fillingim RB, Ohrbach R, Arbes SJ Jr, Tchivileva IE. Effect of treatment expectation on placebo response and analgesic efficacy: a secondary aim in a randomized clinical trial. JAMA Netw Open. 2020;3(4):e202907.
Freedland KE. Purpose-guided trial design in health-related behavioral intervention research. Health Psychol. 2020;39(6):539–48.
Hsu B, Emperumal CP, Grbach VX, Padilla M, Enciso R. Effects of respiratory muscle therapy on obstructive sleep apnea: a systematic review and meta-analysis. J Clin Sleep Med. 2020;16(5):785–801.
The study is funded by the Mind and Life Institute Varela Grant and the University of Florida College of Dentistry Transition to Scientific Independence Postdoc Seed Grant awarded to Steven Pratscher, Ph.D. The funding sources had no role in the design of the study or in writing this manuscript. Any views, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect those of the funders, including the Mind & Life Institute.
Ethics approval and consent to participate
This study was approved by the University of Florida Institutional Review Board (Protocol #202002612). All participants will provide written and signed informed consent prior to enrollment. Study procedures and methods have been approved by the Institutional Review Board at the University of Florida, and all study participants will provide informed consent prior to enrollment.
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The authors declare that they have no competing interests.
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Pratscher, S.D., Sibille, K.T. & Fillingim, R.B. Conscious connected breathing with breath retention intervention in adults with chronic low back pain: protocol for a randomized controlled pilot study. Pilot Feasibility Stud 9, 15 (2023). https://doi.org/10.1186/s40814-023-01247-9
- Breathing practice
- Conscious connected breathing
- Chronic pain
- Chronic low back pain
- Intervention development