Recruitment issues that could not be resolved in a timely manner.

This study aims to assess the effectiveness of perioperative pain neuroscience education (PPNE) in patients who are at risk for unfavorable outcome following surgery for lumbar radiculopathy. Although most of these surgeries are successful, 23-28% of patients report chronic pain and disability following surgery. Many preoperative factors are associated with an unfavorable surgical outcome, including maladaptive cognitive and emotional factors. Yet, current preoperative education, which focuses on anatomy and biomechanics of the lumbar spine, is ineffective in changing those maladaptive factors. PPNE was introduced as an innovative therapy that addresses modifiable risk factors in patients undergoing surgery for lumbar radiculopathy. PPNE reconceptualizes pain, informs patients about their pain development and is well established for improving maladaptive cognitions in several chronic pain-populations. Hence, we hypothesize that PPNE will be more effective than perioperative biomedical education in improving postsurgical quality of life, pain, analgesic use and return to work in patients at risk for unfavorable outcome following surgery for lumbar radiculopathy. First, a multicentric randomized controlled trial will compare the therapy effects of PPNE to perioperative biomedical education in these at-risk patients. Next, the mediating role of changes in maladaptive cognitions, such as fear of movement and pain catastrophizing, on the therapy effect of PPNE will be investigated.

Study rationale: Lumbar radiculopathy is described as uni- or bilateral leg pain which is often worse than back pain, with pain radiating in the related dermatomes and possible associations with sensory and/or motor symptoms or even deficits. Although surgical intervention for lumbar radiculopathy is often considered anatomically successful, several patients undergoing similar surgeries continue to experience pain and disability. Furthermore, patients developing such an unfavorable outcome also report decreased quality of life values, as well as an increase in analgesic use and health care utilization. Such unfavorable outcome is associated with a multitude of preoperative factors, including but not limited to maladaptive cognitive and emotional factors (e.g., fear of movement, pain catastrophizing, anxiety, distress and depression), preexisting chronic pain and long duration of preoperative sick leave. In line with this, it has been suggested that maladaptive psychological factors require special attention and optimization before surgery. Perioperative pain neuroscience education (PPNE) is such an intervention addressing these maladaptive psychological factors, such as fear of movement and pain catastrophizing. Therefore, a study assessing the effectiveness of PPNE on surgical outcome in at-risk patients undergoing surgery for lumbar radiculopathy is warranted.

Rationale for study design: The present study builds on the evidence provided by the study of Louw et al. (2014 & 2016) which was a randomized controlled trial comparing PPNE with no supplemental intervention in patients undergoing surgery for lumbar radiculopathy. As such, we will conduct a multicentric randomized controlled trial investigating the therapy effect of PPNE specifically in patients with lumbar radiculopathy at risk for unfavorable surgical outcome. Doing this we will address several knowledge gaps by comparing two balanced therapy groups (PPNE vs perioperative biomedical education (PBE)), therefore overcoming potential bias due to unbalanced treatment arms, by adding several relevant outcome measures, and by targeting high-risk patients rather than all patients undergoing surgery.

Study objectives: The primary objective is to examine whether PPNE is more effective than PBE in improving postoperative quality of life at 6 weeks follow-up in patients undergoing surgery for lumbar radiculopathy at risk for unfavorable surgical outcome. Secondary objectives include: 1) to explore baseline associations between pain cognitions, quality of life and pain in patients scheduled for surgery for lumbar radiculopathy at risk for unfavorable outcome; 2) to examine whether PPNE is more effective than PBE in obtaining good surgical results concerning quality of life, pain, analgesic use, return to work, self-reported symptoms of central sensitization and pain cognitions at 6 weeks, 6 months and 1 year post-surgery and 3) to reveal the mediating role of changes in pain cognitions in the mechanism behind the therapy effect of PPNE in patients undergoing surgery for lumbar radiculopathy at risk for unfavorable outcome.

Study design: This study is a randomized controlled trial with one-year follow-up using preoperative patient screening based on chronic pain (≥ 6 months), kinesiophobia (Tamp Scale for Kinesiophobia ≥ 37/68) and pain catastrophizing (Pain Catastrophizing Scale ≥ 30/52). Eligible patients undergoing surgery for lumbar radiculopathy will be randomized and receive either the experimental intervention, i.e., PPNE, or the control intervention, i.e., PBE. Follow-up assessments will be organized at 6 weeks, 6 months and 12 months following the surgery.

Patient recruitment: All patients scheduled for surgery for lumbar radiculopathy in one of the participating hospitals will be contacted by telephone by the coordinating investigator. First, patients will be informed about the project and asked if they are willing to participate. When patients agree with participating in the study, they will be screened for potential eligibility using the in- and exclusion criteria. Following the initial screening, patients will have to meet an additional set of presurgical criteria (i.e., chronic pain, pain catastrophizing and kinesiophobia) to assess whether they are at risk for unfavorable surgical outcome, and therefore eligible for inclusion in the study sample. To screen for these presurgical criteria, patients eligible for further screening after the initial telephone interview, will be asked to complete an online survey questioning the three aforementioned criteria. The first page of the online survey will inform the patients once again about the goal of the screening and all patients will have to indicate their consent (by checking a box) before they can proceed to the actual questionnaire.

Randomization and blinding procedures: Following baseline assessments, participants will be randomized to one of both treatment groups. Concealed randomization will be prepared using a stratified permuted block allocation with stratification for treatment center. Randomization will be executed by an independent researcher who is not involved in the recruitment, assessments, treatment provision or statistical analyses. Patients will not know whether the intervention they receive is the experimental or the control intervention, however they will of course be aware of the content of the received intervention. A co-investigator, who will be responsible for baseline assessment and all follow-up assessments, will also be blinded to group allocation. With regard to this, patients will be asked not to communicate with the co-investigator about the intervention they received. The therapists providing the experimental treatment will not be involved in providing the control intervention and vice versa.

Sample size: Sample size was calculated to be 108 (54 per intervention group) based on a medium effect size of 0.6, α of 0.05, desired power of 0.80, an allocation ratio (N2/N1) of 1 and an anticipated loss to follow-up of 20%. A longitudinal pilot study in patients undergoing surgery for lumbar radiculopathy and who were retrospectively selected based on chronic pain (≥3 months), kinesiophobia (Tampa Scale for Kinesiophobia ≥37/68) and pain catastrophizing (Pain Catastrophizing Scale ≥30/52) was performed and evaluated the effect of PPNE on Short-Form 36-item, these results were used to determine the effect size for the sample size calculation.

Statistical analysis: Descriptive and correlation analyses will be performed on the baseline data. An AN(C)OVA repeated measures analysis will be used to evaluate treatment effects (primary and secondary objective). Lastly, a mediation analysis will be performed to examine the potential mediating role of changes in pain cognitions on the therapy effect of PPNE on quality of life.

Inclusion Criteria:

• Scheduled for surgery for lumbar radiculopathy
• Aged 18 years or older
• Willing to comply with pre-determined follow-up
• Speaking and reading Dutch fluently
• No new treatments/medication 3 weeks prior to participation and during the trial
• Having chronic back and/or leg pain ≥ 6 months
• Scoring ≥ 37/68 on the Tampa Scale for Kinesiophobia
• Scoring ≥ 30/52 on the Pain Catastrophizing Scale

Exclusion Criteria:

• Surgery for another condition
• Symptoms of cord compression or bilateral leg pain
• Other chronic illness characterized by chronic pain
• Other chronic rheumatoid, neurological, endocrinological, psychiatric or cognitive disorders
• Indicated cognitive impairment (Scoring ≤11/15 on the 5-min Telephone Montreal Cognitive Assessment)
• Pregnant or have given birth during the past year
• No access to computer, or mobile device at home
• Complications during the surgery

Given the confidential nature of the collected data, the raw data will not be made open access following the study. However, excluding all possible personal identifiable data (e.g., date of birth and date of surgery), the pseudonymized data of all outcome measures (i.e., health-related quality of life, pain intensity, analgesic use, return to work, self-reported symptoms of central sensitization, pain catastrophizing, kinesiophobia and pain hypervigilance), as well as general demographic data (e.g., age, height, weight and education level) will be made available via a data repository with restricted access.

Following the study, the data will be stored at a data repository with restricted access for 10 years.

Only researchers who intend to use and analyze the pseudonymized data for the purpose of scientific research can request access to the data. Additionally, researchers who intend to use the data are required to provide a statistical plan including the predetermined research question and detailing the intended analyses. Also, details regarding the storage of the shared data should be provided to ensure that the researchers took the appropriate measures to establish a secure storage location for the shared data. A request for data access can be send to the central contact person and a data sharing agreement will be signed by both parties.

Only the participant and the person responsible for the monitoring of the baseline and follow-up assessments will be masked.