29 multiple replicates in both cross-sectional and longitudinal studies.81,82 Although normative values are available83 and the technique seems very promising,84 outcomes seem to vary between different research groups and remains a topic of discussion.85 Automated classification shows representative results.86 Pitfalls include the small field of view87 and a lacking consensus on cutoff values.14 Sensory function tests Quantitative Sensory Testing (QST) QST contains a large battery of sensory nerve tests in order to test both large and small sensory fibers.88 QST involves thermal, pressure, vibration and electrical stimulation. The full QST battery assesses thirteen parameters within seven test procedures.89 Since the full QST test is time consuming, thermal threshold testing (TTT) is often selected to test small fiber function.90–92 TTT uses a thermode with a baseline temperature of 320C which increases up to 500C or decreases down to 00C.93 Two methods are available to test for thermal detection and pain thresholds; method of limits (reaction time dependent) and method of levels (reaction time independent). Method of limits starts at the baseline temperature and increases or decreases its temperature. The test-button has to be pressed twice; first when it feels the temperature change and second when the temperature becomes painful. With the method of levels, 2 buttons are available representing yes or no. For each stimulus, the question is asked whether the thermode becomes colder or not.94 With the method of levels, only thermal detection thresholds are determined and no thermal pain thresholds. According to Table 2, normal temperature detection thresholds lay above 410C and below 250C and temperature pain thresholds lay above 450C and below 50C.35 In order to exclude large fiber involvement, nerve conduction studies (NCS) are recommended instead of the other QST test procedures.95 QST improved pain quantification over pain questionnaires and opened new frontiers, beyond NCS capabilities. However, QST also has some limitations. It consists of a set of psychophysical instruments, which requires an alert and focused patient. Also, numerous factors may influence the results, like environmental conditions (seat position, room temperature, illumination and noise level), gender of the tester, instructions provided to the subjects, habituation, cognitive capacity and motor performance.88 Moreover, lack of age- and gender-controlled normative values has limited routine use. Worldwide uniformity in procedures might overcome most of its limitations.96 Microneurography Microneurography measures conduction velocity and other properties of small nerve fibers. A needle with a diameter of 1-5 µm is inserted into a peripheral small nerve fiber.97,98 Microneurography is the only technique which quantifies the sympathetic nerve activity directly.99,100 It is often used to measure muscle sympathetic nerve activity and skin sympathetic nerve activity.101 Some limitations include time-consuming, expensive, requires expertise and strict collaboration with the patient to perform.98,101 Therefore, it is not used in routine clinical practice. Nociceptive evoked potentials With nociceptive evoked potentials, a brief noxious stimulus is applied at the skin to evoke a timelocked response in electroencephalography (EEG) signal.38 Amplitude and latency are outcome measures from the response in the EEG signal. Aδ and C-fibers can be examined separately from each other due to differences in conduction velocity. Noxious stimuli can be applied by the use of a laser, contact heat or intra-epidermal electrical stimulation. When small nerve fibers are damaged, conduction velocities will decrease, resulting in increased evoked potential latency and decreased amplitude.102 2 31 2
RkJQdWJsaXNoZXIy MjY0ODMw