The lack of a gold standard to compare pain mechanism categories (PMCs) in the pain management field represents an urgent research need, and expert consensus according to a systematic review published in Pain.

Mechanism-based pain classification has been advocated to aid clinicians to tailor interventions for people experiencing persistent musculoskeletal pain, including the three PMCs: nociceptive, neuropathic, and nociplastic pain. By devising a systematic review, researchers evaluated the clinical and laboratory-based methods that discriminate between the three PMC categories, synthesized and analyzed the methods, and summarized the strengths and limitations of each method.

A search strategy yielded 11,874 articles, and after excluding duplicates and ineligible articles, 184 publications were included in the review. Data were extracted for 200 methods across 5 methods used to differentiate between PMCs: clinical examination, quantitative sensory testing, imaging, diagnostic and laboratory tests, and pain-type questionnaires.

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For the PMCs, 3 articles discussed how to discriminate between nociceptive, neuropathic, and nociplastic pain. Twenty-two studies (sympathetic n=13, psychogenic n=9) evaluated the discrimination of disputed PMCs.

One hundred and fifty-two (93%) studies discussed clinical examination findings across the domains of subjective pain examination, psychological assessment, and physical clinical examination.

One hundred and thirty-six (83%) studies discussed subjective pain examination and how those studies aid the pain mechanism categories. Within these studies, features such as aggravating and/or easing factors, pain location, and pain characteristics were identified to aid in pain mechanism category discrimination.

Psychological assessment was evaluated in 46 (28%) studies. These methods generally included questionnaires about psychological features; some studies (5%) characterized nociceptive pain with “minimal or absent” psychological features, while evidence of psychological features is used to differentiate nociplastic pain from other pain mechanism categories.

One hundred eighteen (72%) studies included physical clinical examination as a method to aid in PMC discrimination, with 6 identified subthemes: general clinical assessment, general neurological testing, neurodynamic and nerve provocation testing, clinical bedside somatosensory function testing, movement testing, and diagnosis by exclusion. Of these, no single method differentiated the PMCs.

Imaging was covered in 50 (31%) studies to develop 12 themes including X-ray, computed tomography, magnetic resonance imaging (MRI), functional MRI, ultrasound, and others.

Both diagnostic and laboratory testing were discussed in 57 (35%) studies as a method to discriminate between PMCs. Within this domain, 11 methods were identified, including electroneurophysiological testing, diagnostic anesthetic blocks, skin biopsy, biochemical testing, blood flow testing, autonomic testing, urine analysis, quantitative sweat tests, analysis of stem-cell derived neurons, corneal confocal microscopy, and genetic studies.  

The psychometric properties of neuropathic and central sensitization questionnaires are varied within and between questionnaires, with results ranging from poor to excellent. The researchers noted that multicomponent classifications systems have been developed with the purpose of discriminating between PMCs. Some discriminate between the 3 PMCs, subtypes, and a single category.

“This systematic review provides the first comprehensive synthesis of the vast literature regarding methods proposed to aid discrimination between mechanism-based categories of pain experienced in the musculoskeletal system,” the researchers wrote.

Study limitations included those inherent to systematic reviews, the wide type of published articles included and the associated potential for bias, and the use of one reviewer to screen studies, extract data, and review quality, while a second reviewer performed these same steps on only a sampling of articles.

“Building on a framework of convergence of terminology, mechanisms, and characteristics of PMCs related to musculoskeletal pain derived from a recent systematic review, this systematic review provides the most extensive synthesis of methods purported to aid discrimination between clinical and researcher contexts,” the researchers concluded.

“The diverse array of methods in the absence of a gold standard for comparison highlight an urgent need to reach expert consensus.” The study authors added, “This review provides a summary of the state of the literature that can support that aim.”


Shraim MA, Massé-Alarie H, Hodges PW. Methods to discriminate between mechanism-based categories of pain experienced in the musculoskeletal system: a systematic review. Pain. 2021;162(4):1007-1037. doi:10.1097/j.pain.0000000000002113