Central hyperexcitability as measured with nociceptive flexor reflex threshold in chronic musculoskeletal pain: A systematic review

• Published in: Pain (Amsterdam) Vol. 152; no. 8; pp. 1811 - 1820
• Main Authors: Lim, Edwin Choon Wyn, Sterling, Michele, Stone, Andrew, Vicenzino, Bill
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Elsevier B.V 01.08.2011; Elsevier
• Subjects: Biological and medical sciences; Databases, Factual - statistics & numerical data; Diseases of striated muscles. Neuromuscular diseases; Fundamental and applied biological sciences. Psychology; Humans; Medical sciences; Musculoskeletal Diseases - complications; Musculoskeletal Diseases - diagnosis; Musculoskeletal Diseases - physiopathology; Musculoskeletal disorder; Neurology; Nociceptive flexion reflex; Pain; Pain - complications; Pain - diagnosis; Pain - physiopathology; Pain Measurement - methods; Pain Threshold - physiology; Psychomotor Agitation - complications; Reflex - physiology; RIII; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Vertebrates: nervous system and sense organs; Nociceptive flexion reflex; RIII; Pain; Musculoskeletal disorder; Knee; Headache; Nervous system diseases; Variability; Diseases of the osteoarticular system; Central nervous system; Fibromyalgia; Regression analysis; Flexion reflex; Striated muscle disease; Chronic; Hyperexcitability; Whiplash; Neurological disorder
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/j.pain.2011.03.033

Chronic musculoskeletal conditions are increasingly conceived as involving altered central nervous system processing, and impaired nociceptive flexor reflex (NFR) appears to reflect altered central nervous system processing. The primary objective was to synthesize the evidence for impaired NFR in these conditions. The secondary objective was to evaluate the NFR stimuli parameters employed by reviewed studies. Electronic databases: MEDLINE, CINAHL, Embase, PEDro, Google Scholar, and Cochrane library were searched from the mid-1960s to June 2010. Experimental reports were systematically reviewed and meta-analysis (where possible) was performed. NFR thresholds and parameters of NFR stimuli were extracted. Sixteen trials were identified, 11 of which were suitable for inclusion in the meta-analysis. Compared to healthy controls, standardized mean differences in NFR threshold were significantly lower in subjects with primary headache (−0.45; 95% confidence interval [CI] −0.77 to −0.13, P=0.005), fibromyalgia (−0.63; 95% CI −0.93 to −0.34, P<0.0001), knee pain (−1.51; 95% CI −2.10 to −0.93, P<0.00001) and whiplash (−0.73; 95% CI −1.11 to −0.35, P=0.0002). Employed stimuli parameters vary between studies, with inter-pulse duration (P=0.044) being identified by multiple regression analysis as independent predictors of the variability in NFR threshold in healthy controls. The results indicate that there is evidence of central hyperexcitability in people with chronic musculoskeletal pain. Our review also suggests that shorter inter-pulse duration tends to yield smaller variability in NFR threshold. However, further research investigating optimal stimulation parameters is still warranted. Systematic analysis shows that despite variation in measurement parameters, nociceptive flexor reflex is impaired in chronic musculoskeletal conditions, inferring involvement of spinal cord hyperexcitability.