Developing a Chinese medicine syndrome differentiation questionnaire for chronic pain patients who use opioid medications

Chronic musculoskeletal pain (CMP) is common and associated with reduced quality of life, loss of productivity, and increased health expenditures to the patients and the society. Chronic musculoskeletal pain is increasingly managed with opioid medications (OMs) with many and serious adverse effects and CMP is accompanied with comorbidities and non-pain symptoms. Comorbidities increase the burden to health management and deteriorate quality of life.<br><br>Chinese medicine (CM) has been used to treat CMP and has its own theory and understanding of CMP. Chinese medicine diagnoses CMP into sub groups called CM patterns based on the presenting pain and non-pain symptoms of CMP patients. However, such an approach has not been evaluated by clinical trials to determine the value of pattern identification in the CM management for CMP, particularly for users of OM for CMP control.<br><br>In order to establish a basis for further research into CM for CMP, there is a need to identify the CM patterns of CMP and assess their differences with clinical outcomes measured by validated tools.<br><br>The Objectives of this thesis were to:<br><br>1) identify the comorbidities and symptomatologies of CMP through a systematic review;<br><br>2) develop and validate a Chinese medicine Pain Questionnaire (CMPQ) for pattern identification in CMP patients who are OM users;<br><br>3) differentiate the CM patterns of CMP who use OM for pain control using cluster analysis; and determine the cluster differences in demography, pain intensity, OM consumption, depression, quality of life, and disability; and<br><br>4) determine the differences between CM patterns and clinical outcomes of electro acupuncture (EA) based on the change in CMPQ symptoms, pain intensity, OM consumption, depression, and quality of life.<br><br>Method: A systematic review was carried. Major English databases were searched and restricted to English and Chinese languages publications. Chinese medicine literatures were searched and symptoms and signs related to CMP were extracted. The development of CMPQ was embedded in another electro acupuncture trial. CMP participants were recruited if they use OM and wish to reduce their OM usages. Trial participants were randomised into either real electro acupuncture (EA), sham EA, or no EA groups.<br><br>The CMPQ data were analysed for validities and reliabilities. Participants’ data were analysed using principal component analysis and K-means cluster analysis. Analysis of variance, multivariate analysis of variance, and Chi square were used to assess the association between the clusters, their demography, and other commonly used outcome measures. Cochran’s Q test was used to assess the changes within the dichotomous CMPQ symptoms.<br><br>Results: Major English databases were searched for the systematic review and 72 studies were included with 61 of them being categorised into three main groups: chronic spinal pain, arthritis, and fibromyalgia. The findings showed the association between CMP and comorbidities and accompanying pain or non-pain symptoms for chronic spinal pain and arthritis but not for fibromyalgia. Chronic spinal pain (20 studies) was associated with (odds ratio 1.33-7.9) arthritis, headache/migraine, depression, and panic attacks/disorder, hypertension, heart diseases, general anxiety disorder, mood disorder, alcohol use disorder, and digestive ulcer. Arthritis (37 studies) was associated with (odds ratio 1.48 – 8.7) chronic spinal pain, depression, panic disorder, post traumatic stress disorder, heart disease/attack, asthma, headache, any chronic pain, and any physical disease. The current systematic review revealed that 15 fibromyalgia studies did not report odds ratio data on the same comorbidities. The association between comorbidities and fibromyalgia remains unconfirmed. Fibromyalgia patients were found to suffer from fatigue (95%), depression/depressiveness (90.9%), anxiety (77.7%), irritable bowel syndrome (62%), and irritable bladder (58%).<br><br>Chinese medicine literature was reviewed and a draft CMPQ was developed. Chinese medicine pain questionnaire contained 187 questions in the following six domains: pain regions, pain quality, pain rhythm, pain aggravators, pain alleviators, and other accompanying symptoms. These questions were reviewed by a group of CM researchers for face and content validities. The draft CMPQ was subsequently tested amongst CMP who used OM for pain control. The CMPQ was completed by these subjects four times throughout the trial. In total 108 participants were recruited. The participants mostly had seven or more pain sites (55.6%). Many of them had pain in the back regions (41.6% to 78.2%), lower limbs (40.6% to 48.5%), and shoulder (41.60%), and Most of them had sharp pain (58.4%), pain at a fixed location (42.6%), pain all the time (63.4%), and worse pain when first getting up (42.6%). They were often accompanied with: feeling tired easily (69.20%), insomnia (59.40%), limited movement (56.40%), poor concentration (55.40%), poor memory (48.50%), feeling depressed (47.50%), irritable (45.50%), constipation (44.50%), and low libido (41.60%). Chinese medicine pain questionnaire demonstrated good face validity, content validity, test-retest reliability (Correlation coefficient=0.846 for overall questionnaire), and internal consistency (Cronbach’s α=0.931).<br><br>The CMPQ data gathered throughout the trial was analysed using principal components analysis to extract 36 factors from the five CMPQ domains (except for pain region). Then the extracted factors were clustered using K-means cluster analysis into six clusters. Cluster four (n=48) and cluster five (n=41) had the largest number of participants and they were diagnosed as CM “heat pattern” (cluster four), and “cold with deficiency pattern” (cluster five) respectively by the CM cluster analysis group experts. Of the remaining clusters, only clusters two and six had more than one participant.<br><br>Multivariate analysis of variance on their demographic data showed cluster four had the shortest mean pain history (10.14 years) whereas cluster six had the longest pain history (24.71 years). The comparison between the two CM patterns showed the CM “heat pattern” was associated with the better quality of life and mild depression whereas the CM “cold with deficiency pattern” was associated with worse quality of life and moderate depression.<br><br>The baseline and end of treatment weeks CMPQ data were used. The comparison was within individual changes rather than between group changes. It was shown that real EA was the only group without symptom deterioration, sham EA and no EA both had two symptom deteriorations. Sham EA was the group with most symptom improvements (nine symptoms) followed by no EA (four symptoms) and real EA (two symptoms).<br><br>To identify which pattern responded better to real EA, CM heat pattern and CM “cold with deficiency” pattern were used as they had more participants. This comparison was within individual changes rather than group changes. The heat pattern subgroup reported improvement in one more symptom on CMPQ in response to real EA than the cold with deficiency pattern subgroup.<br><br>Baseline and end of treatment weeks data of pain intensity, OM consumption, depression, and quality of life of the three treatment groups and the two CM patterns were compared. These were group mean comparisons and not changes within individuals. There were no differences between the three treatment groups, neither was there any difference in how the two CM patterns responded to the three treatments.<br><br>In conclusion, this project employed an evidence-based medicine approach to identify symptom presentation in CMP patients who use OM for pain control, developed and validated the CMPQ for clinical sub grouping guided by CM theory and diagnosis. Furthermore, a preliminary analysis on potential relationship between CM patterns and clinical outcome was conducted as part of a multicentre RCT on EA for CMP who used OM. The finding of distinct heat and cold with deficiency patterns in CMP indicates the importance of incorporating some form of heat therapy, such as moxibustion, into future acupuncture studies for chronic pain.<br><br>The main limitation of this thesis is the small sample size during the evaluation of treatment effect of the three treatments and when the real EA group was further sub grouped into the two CM patterns. Further validation of the CMPQ in larger and different study populations is needed to determine the clinical benefit of CM patterns in clinical practice of EA for CMP. In addition, the use of likert scales instead of a dichotomous format to capture subtle changes after intervention is recommended. It is anticipated that a validated CMPQ may enhance the clinical benefit of multidisciplinary approach for the management of CMP.<br><br>1. Xue CC, Helme RD, Gibson S, Hogg M, Arnold C, Somogyi AA, et al. Effect of electroacupuncture on opioid consumption in patients with chronic musculoskeletal pain: protocol of a randomised controlled trial. Trials. 2012;13:169. doi: 10.1186/1745-6215-13-169<br><br>