Prevalence and pattern of co-occurring musculoskeletal pain and its association with back-related disability among people with persistent low back pain: protocol for a systematic review and meta-analysis

Musculoskeletal disorders are highly ranked among public health problems globally and is the second most common cause of years lived with disability (YLDs) [1]. Consequently, musculoskeletal disorders markedly affect individual’s social participation and quality of life. Among these conditions, low back pain causes approximately 10% of the total YLDs globally and is the most significant cause of severe long-term pain and physical disability and is strongly associated with poor self-rated general health [1‐3].

Low back pain can range from shorter acute episodes to a trajectory of fluctuating episodes and, for some, severe and persistent pain [4]. Individuals with persistent low back pain commonly have a broad range of other health conditions and diseases, including co-occurring musculoskeletal pain in other body sites [5‐7] and comorbidities such as sleep disorders, anxiety, and depression [8, 9]. The CUPID study, which included 12,410 workers from 18 countries, demonstrated that individuals who report musculoskeletal pain at one site are twice as likely to report pain at another anatomical site, in particular at anatomically adjacent sites and corresponding bilateral sites, when compared to people not reporting musculoskeletal pain [10]. Likewise, a large-scale study with more than 100,000 persons in USA found a significantly higher prevalence of comorbidities, musculoskeletal and neuropathic pain conditions, and greater use of pain-related medications in people with persistent low back pain compared to controls [8]. For some individuals, pain in multiple sites may be persistent over the adult lifespan [11] with severe negative impact on functional abilities and disability [12].

Although the presence of comorbidities can significantly affect health-related quality of life [13], symptom severity [13, 14], treatment outcomes [15], and prognosis [16, 17], current clinical guidelines on the management of musculoskeletal disorders usually provide recommendations focused at one region or single joint complaints [18]. One plausible reason is that, to date, research has failed in determining the prevalence and patterns of co-occurring musculoskeletal pain in persons with persistent low back pain and its association with disability. Better understanding of these can potentially guide clinicians in regard to the type, format and dosage of pain management. It could also potentially inform the design of targeted interventions for those with persistent multisite musculoskeletal pain conditions [8]. To our knowledge, no systematic review has been carried out to critically appraise and summarize the literature on the prevalence and pattern of co-occurring musculoskeletal pain among people reporting persistent low back pain and its potential association with age, sex, or back-related disability.

The primary objective of this systematic review is to identify the prevalence of co-occurring musculoskeletal pain among people with persistent low back pain. In addition, we will seek to establish whether there are any specific patterns of co-occurring musculoskeletal pain in people with persistent low back pain. Finally, we will investigate if there is an association between pain patterns, numbers of pain sites, age, sex, and back-related disability.

The following research questions will be addressed in this systematic review:

We have prepared and presented this protocol according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P 2015 Guidelines) [19], and its populated version for this journal is provided as Additional file 1. This systematic review protocol is registered in the international prospective register of systematic reviews (PROSPERO) with registration number CRD42017068807.

Studies will be included in this systematic review if they have met all inclusion criteria and will be excluded if they have met at least one of the exclusion criteria below.

Inclusion criteria

Exclusion criteria

A comprehensive search for relevant studies, with no date limit or publication and language or geographic restriction, will be performed in the following bibliographic databases: MEDLINE and Embase (via Ovid), CINAHL, and Scopus for forward citation tracking. We will combine search term groups covering the following domains: back pain, co-occurring musculoskeletal pain, combined with a focus group that emphasizes study design. The search will not include the term “back-related disability,” but we will run separate analyses for those studies that have assessed this. A pilot search has been done on the search terminology to ensure its all-inclusiveness. Reference lists of retrieved articles and reviews will be scrutinized and forward citation tracking of key articles conducted in order to identify any further studies. Communication with content experts will also be used to identify any additional studies not identified in the computerized search. PROSPERO will be searched for ongoing or recently completed systematic reviews. Gray literature of epidemiological studies will be searched through the reference lists, content experts, and content websites (e.g., HUNT database [www.​ntnu.​edu/​hunt], System for Information on Grey Literature in Europe, previously SIGL [www.​opengrey.​eu site]). Automated search updates will be set up in each database to ensure we include the latest hits in the field. Additional file 2 presents the search strategy designed for MEDLINE. Studies that are identified by our search strategy will be retrieved and managed using Endnote X8 (Thomson Reuters, Philadelphia, PA, USA).

Relevant records will be selected through a two-stage screening process by three independent reviewers (CKO, MJ, and TC). In the first stage, titles and, subsequently, abstracts will be screened with the reviewers blinded to each other’s selection. Disagreements will be discussed and resolved by a fourth independent author (BN) if necessary. The studies considered not to be relevant or that clearly do not meet the inclusion criteria will be excluded, and full-text articles of the remaining studies will be obtained. Studies involving the topic, but with uncertain relevance for this study, will be taken to the second stage for further considerations.

In the second stage, the three reviewers (CKO, MJ, and TC) will make the final selection based on screening of the articles in full text against the eligibility criteria. Citation tracking will be performed from the retrieved full-text articles and previous systematic reviews. If necessary, additional information will be sought from study authors to resolve questions about eligibility. Consensus meetings will be used to resolve any disagreement or, if required, by consulting a fourth reviewer (JH). Reasons for excluding literature will be recorded. A flowchart will be produced to facilitate transparency of the process.

Data from the included articles will be extracted by two independent author pairs (CKO + MLF and MJ + JH), each pair including an experienced reviewer using a form. Disagreements will again be resolved first by discussion or if necessary by a third independent group of reviewers (TC, BN, and PJM).

Data extraction will include (1) first author, publication year, country, and language; (2) study topic, objective(s), and design; (3) time of study, mode of data collection, and type of population; (4) total sample, participation and response rate, cohort characteristics such as sex distribution, median/mean age, ethnicity, and socioeconomic status; (5) definition of low back pain; (6) presence and severity of back-related disability reports; (7) number and location of co-occurring musculoskeletal pain sites and patterns of co-occurring musculoskeletal pain and other information for assessment of risk of bias. We will attempt to contact study authors by e-mail when additional information is required, for example, due to missing data. To reduce potential errors, the data extraction form will be tested on randomly selected studies identified through the pilot search and amended accordingly.

Assessment of methodological quality and risk of bias of the included studies will be conducted at the study level using a modified version of the Risk of Bias Tool for Prevalence Studies (see Additional file 3). This tool was developed by Hoy et al. and found to have high inter-rater agreement [20]. We have modified it slightly for the purpose of this systematic review; item 6 was defined for low back pain only, and we left the example in item 7 open with regard to which questionnaire that was used apart from that it must have been validated. Individual items will be rated as “Yes” if the criterion is fulfilled. Otherwise, if the design of the study is not applicable or if there is insufficient information in the study to permit a judgment for a particular criterion, then it will be noted as “No.” Each study will be given an unweighted methodological score, expressing the proportion of fulfilled criteria out of the total number of relevant criteria. At the end, the overall risk of bias will be determined, not as an overall numeric rating, but based on the raters’ consensus given the responses to the preceding 10 individual items in this tool. This is consistent with the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) and Cochrane approaches [20‐22]. All studies will be included in the evidence synthesis, but those with low risk of bias will be considered separately. All authors, which consist of both professors with experience in systematic reviews and risk of bias assessment and three PhD students, will be involved in the assessment of risk of bias.

The results of the data extraction and risk of bias assessment will be summarized in tables, separately for people seeking care in primary care, working, and general population samples. Our purpose is not to analyze the influence of different work exposures but to assess whether the patterns between working, care seeking, and general population samples are different. The proportion of participants with low back pain reporting co-occurring musculoskeletal pain at other anatomic sites as well as the reported number of co-occurring musculoskeletal pain sites will be described as prevalences. If studies are considered sufficiently homogenous, pooled proportions will be calculated for any additional musculoskeletal pain site, as well as the median number of additional sites reported by included studies. Standard errors will be calculated as the square root of the variance of the proportion, and pooling of results will be attempted using the inverse variance weighting method and random effects model. Statistical heterogeneity will be determined using the I ² statistic. STATA will be used for pooled analysis.

Patterns of co-occurring musculoskeletal pain, in terms of the distribution of pain sites or the probability of pain in other anatomic regions, will be described when possible according to the definition of low back pain (symptom duration). In the case of sufficiently homogenous studies, the reported measures of association (e.g., odds ratio), between the pain pattern and/or number of pain sites and age, sex, and/or back-related disability, will also be pooled. Moreover, the impact of age and sex on the prevalence and pattern of co-occurring musculoskeletal pain will be described and pooled if enough studies have reported these associations. Results will be presented in figures and/or tables where appropriate.