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The Magnitude of Offset Analgesia as a Measure of Endogenous Pain Modulation in Healthy Participants and Patients With Chronic Pain

A Systematic Review and Meta-Analysis

Szikszay, Tibor M., MSc*; Adamczyk, Waclaw M., MSc*,†,‡; Luedtke, Kerstin, PhD*,‡

doi: 10.1097/AJP.0000000000000657
Review Articles

Objective: Offset analgesia (OA) is a test paradigm increasingly used to estimate endogenous pain modulation characterized by a disproportionally profound analgesia after a small decrease of a heat stimulus. This systematic review and meta-analysis examined the magnitude and difference of OA in healthy participants and chronic pain patients.

Materials and Methods: Controlled trials, case-control studies, cross-sectional studies, case-series or other observational studies evaluating the effect of a ±1°C offset trial in healthy controls and patients with chronic pain were searched in PubMed, Web of Science, CINAHL, PEDro, PsycINFO, and Cochrane CENTRAL. An additional hand search was conducted. Studies fulfilling the eligibility criteria were independently assessed for methodological quality with the Downs and Black scale by 2 reviewers.

Results: Twenty-six studies (healthy participants n=758; chronic pain patients n=134) were included in the qualitative synthesis and 12 in meta-analyses (healthy participants n=366; chronic pain patients n=73). A significant difference between offset and constant temperature trials was found for continuous pain intensity rating immediately after a 1°C decrease in temperature (−0.46 [visual analogue scale, 0 to 10]; 95% confidence interval, −0.75 to −0.17; P=0.002), but not after a fixed time period of 5 seconds. Furthermore, a significant difference of the magnitude of OA between chronic pain patients and healthy controls was calculated (−29.9%; 95% confidence interval, −40.3 to −19.5; P<0.00001).

Discussion: Results indicate that pain-free participants show a larger OA response when rating pain continuously compared with individuals with chronic pain.

*Pain & Exercise Research Luebeck, University of Luebeck, Luebeck, Germany

Department of Kinesiotherapy and Special Methods in Physiotherapy, The Jerzy Kukuczka Academy of Physical Education, Katowice

Pain Research Group, Institute of Psychology, Jagiellonian University, Krakow, Poland

W.M.A. is supported by the scholarship awarded within grant #2014/14/E/HS6/00415 funded by the National Science Centre in Poland and by the ETIUDA scholarship provided by National Science Center in Krakow (Poland) (2017/24/T/HS6/00329). The remaining authors declare no conflict of interest.

Reprints: Tibor M. Szikszay, MSc, Department of Orthopaedic and Trauma Surgery, Academic Physiotherapy, University of Lübeck, Ratzeburger Allee 160, Lübeck 23562, Germany (e-mail:

Received May 18, 2018

Received in revised form September 6, 2018

Accepted September 11, 2018

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