Background: Complex regional pain syndrome (CRPS) is a chronic spontaneous pain condition of a limb following inciting events such as fracture or surgery. Pain in CRPS is disproportionate in magnitude or duration to the typical course observed following the inciting event. CRPS is characterized by diverse clinical features including autonomic, immune, and sensorimotor changes. CRPS diagnosis is currently based on the Budapest criteria and prior to 2012 was based on older 1994 IASP criteria. Different CRPS phenotypes have been established including CRPS-I and II and warm and cold CRPS. Clinical and patient phenotypic factors such as upper versus lower limb CRPS and male versus female sex may also influence the condition. This diversity in the diagnostic criteria and clinical picture has hindered the development of an effective treatment strategy. Thus, this review aimed to study the impact of diagnostic criteria and different phenotypes on quantitative sensory testing (QST) outcomes in patients with CRPS. Databases: Eight databases were searched based on a previously published protocol. Thirty-eight studies comparing QST outcomes on the affected side between CRPS-I versus II, warm versus cold CRPS, upper limb versus lower limb CRPS, and males versus females, as well as studies using Budapest criteria versus older IASP criteria, were included. QST outcomes available included. QST outcomes available included thermal, mechanical, vibration, and electrical detection thresholds; thermal, mechanical, pressure, and electrical pain thresholds; wind-up ratio; mechanical pain sensitivity; allodynia; paradoxical heat sensation; and pain ratings. Results: Out of 38 studies identified (15 of low quality, 22 of fair quality, and 1 of good quality), three studies investigated the differences in QST outcomes between a total of 516 patients with CRPS-I and 88 patients with CRPS-II revealing no significant differences between the two CRPS subtypes on any of the QST outcomes. Four studies permitted comparing QST results in 236 patients with warm CRPS to 121 patients with cold CRPS while results indicated a dominant sensory gain in thermal and mechanical pain thresholds, enhanced paradoxical heat sensation, and dynamic mechanical allodynia in warm CRPS, with cold CRPS demonstrating primarily a thermal and mechanical sensory loss. Three studies permitted comparison of QST profiles in 233 patients with upper limb CRPS versus 84 patients with lower limb CRPS revealing comparable results across upper and lower limb CRPS with no significant differences noted on any QST outcome. Examination of two studies reflecting 123 male CRPS patients and 415 female CRPS patients indicated that females with CRPS have a significantly larger gain of PPT than observed in males, with CRPS patients of both sexes showing QST profiles that were statistically similar to healthy subjects. Finally, CRPS diagnosed using Budapest criteria (n = 1769 patients) showed a significant loss of thermal and mechanical sensation but with a gain in thermal and mechanical pain, with no significant heterogeneity and moderate quality of evidence.  Although CRPS diagnosed using the 1994 IASP criteria (n = 493 patients) showed almost the same sensory profile as those meeting Budapest criteria, there was significant heterogeneity and low quality of evidence. Conclusion: CRPS-I and II, upper and lower limb CRPS, and males and females with CRPS display a comparable pattern of sensory changes, potentially indicating similar underlying pain mechanism.  The most prominent differences observed were between warm and cold CRPS.  While warm CRPS showed predominant primary thermal and mechanical hyperalgesia, cold CRPS showed predominant thermal and mechanical sensory loss. Diagnostic criteria used did not appear to influence QST results. However, the Budapest criteria showed a more consistent QST profile than the older IASP criteria. Identifying CRPS and patient phenotypes that better reflect its underlying sensory manifestations might result in more effective treatments (via precision medicine approaches) and better quality of life for CRPS patients.  

Keywords: CRPS; phenotype; quantitative sensory testing; sensory profile