1. 2016;19;307-326An Overview of Offset Analgesia and the Comparison with Conditioned Pain Modulation: A Systematic Literature Review
   Systematic Review
   Eva Bertel, MSc, Linda Hermans, MSc, Patrick Calders, PhD, Jessica Van Oosterwijck, PhD, Ellen Verschelde, MSc, and Mira Meeus, PhD.

BACKGROUND: Offset analgesia (OA) is an increasingly described phenomenon to measure endogenous pain inhibition, in which a greater decrease in pain intensity is experienced than would be predicted by the decrease in painful stimulation. The temporal filtering in this OA phenomenon differs from the spatial filtering in the commonly described conditioned pain modulation (CPM). Yet, the knowledge on the efficacy of OA in chronic pain patients is scarce, compared to CPM efficacy.

OBJECTIVE: This systematic review has been conducted to provide an overview of the current knowledge regarding OA, and to compare it to CPM.

STUDY DESIGN: A systematic review of research studies that investigated the application or mechanisms of OA.

SETTING: The present study took place at Ghent University and the University of Antwerp.

METHODS: This systematic review follows the PRISMA guidelines. The electronic databases Pubmed and Web of Science were searched in January 2015. Full text clinical reports addressing OA were included. The checklists for randomized controlled trials, case-control studies, and cohort-studies provided by the Dutch Institute for Healthcare Improvement and the Dutch Cochrane Centre were used to assess methodological quality. The articles received a level of evidence A1, A2, B, C, or D, based on study design and risk of bias. These levels were used to determine the strength of conclusion (level 1 to 4).

RESULTS: Seventeen articles met the inclusion criteria. Sixteen studies used quantitative sensory testing to provoke OA; however, differences in protocols are present.  OA can function as a non-opioid mediated assessment tool for endogenous pain inhibition, and activates brain regions such as periaqueductal gray (PAG), dorsolateral prefontral cortex, insula, medulla, pons and cerebellum, indicating strong brain derived pain modulation. The primary somatosensory cortex is, conversely, less activated during OA. OA is decreased in neuropathic patients. Nonetheless, evidence for the influence of individual factors on OA is limited. OA and CPM seem to rely on different mechanisms.

LIMITATIONS: Search strategy was taken wide, wherefore a large variety of research perspectives were included.

CONCLUSIONS: This systematic review displays OA as a temporal filtering mechanisms that is more brain-derived compared to the spatial assessment method CPM. There is strong evidence for reduced OA in neuropathic patients, however, evidence regarding OA in (sub)acute and central sensitization patients, and the influence of personal factors on OA is currently scarce and needs further investigation.