Association Between Conditioned Pain Modulation and the 4-week Response to Spinal Mobilization in Adults With Chronic Neck Pain

It has been proposed that neck joint mobilization (JM) [also known as spinal mobilization (SM) of the neck] reduces pain by targeting conditioned pain modulation (CPM) Two studies support the theory that pain relief from JM is the result of processing occurring in the brainstem, the region where CPM is housed. A study found that one exposure of JM normalized impaired CPM and reduced pain. Another study suggested that CPM and JM may share a common CNS pathway from the brainstem to the spinal cord. If so, this may explain the mechanism by which JM relieves pain. Understanding these relationships may allow clinicians to better target treatment to those who may benefit from a JM intervention, potentially reducing the burden associated with chronic neck pain. The purpose of this study is to explore the relationship between CPM and clinical outcomes following JM in those with mild chronic neck pain. This is the first study investigating these relationships.

SPECIFIC AIMS Aim 1: To determine the impact of one JM treatment on CPM and clinical outcomes in patients with chronic neck pain and associated disorder type I (NAD I) or mild neck pain.

Aim 2: To explore these relationships longitudinally. HYPOTHESES [Primary hypotheses]

1. Baseline CPM is significantly associated with baseline outcomes: (a) pain (Numeric pain rating scale or NPRS), (b) perceived disability (Neck disability index or NDI), and (c) perceived recovery (global perceived recovery or GPR).
2. Baseline CPM is associated with longitudinal trend in outcomes: pain (NPRS), perceived disability (NDI), and perceived recovery (GPR)
3. Change in CPM post-JM is associated with longitudinal trend in outcomes: pain (NPRS), perceived disability (NDI), and perceived recovery (GPR)

RESEARCH QUESTIONS

1. What is the baseline CPM in a community sample of individuals with chronic mild neck pain (CNP)?
2. What is the prevalence of impaired CPM at baseline in a community sample of individuals with CNP?
3. In the subgroup of CNP with impaired baseline CPM readings, what proportion has normalized CPM readings, immediately following JM?

EXPERIMENTAL DESIGN AND METHODS Study design. A prospective, longitudinal, cohort study with intervention Sample size. 31 participants were enrolled. Subject recruitment. Participants were recruited via (1) emails sent to the Sacred Heart University (SHU) and Azusa Pacific University community; (2) flyers posted in physical therapy clinics within 30 miles of SHU, and (3) social media advertisements. All recruitment materials specified the study details. Potential subjects who responded were screened by research assistants over the phone, via email, or via a QR coded questionnaire embedded in the flyer to determine eligibility based on the inclusion and exclusion criteria. Patients who met the inclusion criteria were invited to meet with the research assistants, who explained the study and obtained informed consent. Eligible participants were instructed to wear non-restrictive clothing and to refrain from taking analgesics, serotonin norepinephrine reuptake inhibitors (SNRIs), and opioids for 24 hours before CPM data collection.

Venue. Sacred Heart University and Azusa Pacific University physical therapy departments Demographic and clinical variables. Demographic and clinical variables were collected, including age, sex, body mass index (BMI) (calculated based on weight and height), and pain medications (analgesics, SNRIs, opioids). A critical factor in determining the success or failure of conservative care is healthcare utilization (pre- and post-JM). The total number of visits during the study period was tabulated.

Procedure/Methods. The principal investigator (PI) trained assistants/associates to facilitate PI blinding. Patients who consented were assessed for baseline CPM, NDI, and NPRS.

The PI has been practicing orthopedic physical therapy for more than 20 years. He is a manual therapy fellowship-trained and board-certified orthopedic physical therapy clinical specialist. Prior to the baseline CPM assessment, the assistant took the blood pressure and heart rate of the subject, and the investigator conducted a clinical examination assessing the active range of motion and a manual examination to identify the most painful segmental level using both the unilateral postero-anterior (PA) and antero-posterior (AP) oscillatory JM techniques and to familiarize the patient with these two JM techniques which were performed as intervention. Following baseline CPM assessment, there was a 15-minute rest period when the PI provided information on the natural history of neck pain, how JM is believed to work, and the ability to fully participate in usual activities after treatment. Patients were also told to avoid other JM or exercise treatments during the 4-week follow-up period. Next, the PI provided grade III unilateral PA and AP oscillatory JM (5 minutes of PA and 5 minutes of AP in random order based on the random sequence for the CPM measurement such that #1 is for PA and #2 or #3 is for AP) for a total of 10 minutes to the patient's most painful cervical spine segment/s. This dose of JM is based on the work of a study whose authors demonstrated improved pain and global perceived effect. Immediately following JM, research team member #2 reassessed CPM (called post-JM CPM) and later subtracted it from the baseline CPM reading. This is hereby referred to as "change in CPM." After the associate investigator measured post-JM CPM, the participant's blood pressure and heart rate were measured a second time as JM has been shown to affect these vital signs. The purpose was to ensure that was no adverse cardiovascular response to the intervention. At 2 days, 2-, and 4-weeks following JM, a research team associate made a follow-up phone call, sent a text reminder, and/or email request to examine the NPRS score, NDI, GPR, and other clinical variables (e.g., pain medication use, number of healthcare visits related to neck pain). Participants were reminded to avoid receiving JM or exercise interventions for the 4 weeks study period.

To maintain the fidelity of the intervention and protocol, another professor of orthopedic physical therapy (who taught JM for more than 5 years) randomly observed the data collection processes and treatment administration.

Statistical analysis. The characteristics of subjects, including demographics and baseline clinical measurements, were summarized using descriptive statistics, the median, and interquartile range for continuous variables (e.g., age, CPM, NPRS, GPR, NDI, and BMI) and percentages (counts) for categorical variables (ex. sex). All statistical tests were two-sided, and a value of p<0.05 was considered statistically significant. All continuous outcome variables were checked for normality using the Shapiro-Wilk test prior to the statistical analyses.

For hypotheses 1 a linear regression model was used to evaluate the potential association between baseline CPM and three dependent variables (NPRS, NDI, GPR) in a univariate manner and then a multivariate linear regression manner.

For hypotheses 2 and 3, a linear mixed-effect regression (MEM) model was used to evaluate whether baseline CPM or a change in CPM (respectively) is associated with a longitudinal trend in change in pain, GPR, or function (NDI) with baseline as the reference, at 2-day, 2 week, and 4 week follow up adjusting for patient baseline demographics (age, sex, and BMI). The MEM was specified with random intercepts and slopes such that a linear trajectory representing outcome values was compared. Individual-level specific intercept and slopes over the period of follow-up were included as random effects, while other covariates were modelled as fixed effects. All models were adjusted for other baseline clinical (including CPM) and demographic confounders. Residual-based diagnostics were used to evaluate the validity of model assumptions. Secondarily, to test hypotheses 2 and 3 for single time points, linear regression analyses were performed with univariate analyses conducted first, and if the cutoff p-value of 0.10 was met for a variable, then the multivariate analysis followed. Once included in the multivariate model, a p-value of < 0.05 was considered significant.

For research question #1, descriptive statistics were used to answer the question regarding the baseline CPM levels in the study sample. Research questions #2 and #3 were answered by examining the proportions of participants with impaired CPM at baseline and from this subgroup, determining how many have normalized CPM post-JM.