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Table 6 Overview test 1ā€“12 First round

From: Tests for central sensitization in general practice: a Delphi study

Tests 1ā€“4 are quantitative sensory tests (QST) used to measure hyperalgesia, allodynia and temporal summation (TS). These tests comprise different kinds of stimulation.

Test 1 (electric toothbrush): this test measures vibratory stimuli, this can cause mechanical and thermal stimulation

Test 2 (heat and cold): a thermode applies heat and cold stimuli to the body.

Test 3 (pressure pain thresholds): an algometer performs pressure stimulation on different parts of the body and pressure pain thresholds (PPT) and/or pressure tolerance thresholds are measured.

Test 4 (electrical pain and reflex thresholds): after applying electrical stimuli, electrical pain and reflex thresholds and intensity levels of sensations are measured.

Tests 5ā€“7 are two different QSTĀ testsĀ together to measure conditioned pain modulation (CPM). In CS we expect a smaller reduction of the perceived intensity of the test-stimulus due to reduced inhibition of descending control.

Test 5 (ischemia and PPT): inflating an occlusion cuff, comparing pressure pain prior to and during cuff inflation.

Test 6 (cold and PPT): applying cold water in a bucket, comparing pressure pain prior to and during the application of cold water.

Test 7 (heat and cold): applying cold water in a bucket, comparing pain of heat stimulation prior to and during the application of cold water.

Test 8 and 9 are tests, which like tests 5ā€“7, reflect dysfunction of the ascending and descending pathways. Test 8 (the nociceptive flexion reflex (NFR)): a protective withdrawal reflex, it measures an increase in the activation of the proximal muscles and this can be considered as a marker of delayed inhibition. The NFR is recorded with an EMG device, mostly on a nerve in the calf (sural nerve) and electromyographic responses are recorded using a pair of surface electrodes placed over the tendon of a muscle in the upper leg (biceps femoris) on the same side.

Test 9 (the cutaneous silent period (CSP)): this test shows the delayed inhibition of the grasping muscle and this also can be seen as a marker of this delayed inhibition [35, 36]. The CSP is a brief pause in muscle action potentials following strong stimulation of a cutaneous nerve during a sustained voluntary contraction.

Test 10 (interleukin 8 (IL-8)): this is a laboratory test of the level of the cytokine IL-8. Increased serum levels of cytokines as TNF-alpha and pro-inflammatory interleukins (Il-1, IL-6, IL-8) and reduced anti-inflammatory interleukins (IL-4, IL-10) might lead to neuroinflammation, e.g. of the glia cells, and thus are indicative of dysregulation of the immune system in relation to CS [8]. We expect an increased serum level of IL-8 in patients with CS-related symptoms and this can be measured with a blood sample that has to be processed in a lab.

Test 11 (brain-derived neurotrophic factor (BDNF)): this is a laboratory test of the level of the neurotrophin BDNF. An increase of neurotrophins, e.g. glutamate, substance P, calcitonin gene-related peptide (CGRP) and BDNF, is described as characteristic of CS. In this test BDNF is analyzed in a blood sample, the lab needs equipment for ELISA processing [26].

Test 12 (the Central Sensitization Inventory (CSI)): a self-report questionnaire with two parts. Part A consists of 25 statements relating to current health symptoms, rated on a 5-point scale, resulting in 0-100 points. Part B (which is not scored) asks if one has previously been diagnoses with one or more specific disorders, including seven separate central sensitivity syndroms (CSS) like fibromyalgia, chronic fatigue and irritable bowel syndrome and three CSS-related disorders. It is used both as screening instrument and as treatment outcome measure to identify CS-related symptoms in patients [37, 38]. A cut-off point of 40 is generally used to differentiate between healthy controls and persons with CS-related symptoms.