http://informahealthcare.com/smr ISSN: 0899-0220 (print), 1369-1651 (electronic) Somatosens Mot Res, 2014; 31(4): 198–203 ! 2014 Informa UK Ltd. DOI: 10.3109/08990220.2014.914485
ORIGINAL ARTICLE
Reliability study of thermal quantitative sensory testing in healthy Chinese Ruixia Wang1, Linlin Cui1, Weina Zhou1, Chen Wang1, Jinglu Zhang1, Kelun Wang2,3, & Peter Svensson4 1
Orofacial Pain & TMD Research Unit, Institute of Stomatology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China, Center for Sensory–Motor Interaction (SMI), Aalborg University, Aalborg, Denmark, 3Stomatological School and Hospital, Nanjing Medical University, Nanjing, China, and 4Section of Clinical Oral Physiology, School of Dentistry, Aarhus University, Aarhus, Denmark
2
Abstract
Keywords
Background: Test–retest reliability is important to establish for any diagnostic tool. The reliability of quantitative sensory testing (QST) in the trigeminal region has recently been described in Caucasians as well as differences in absolute thresholds and responses between Caucasians and Chinese. However, the test–retest reliability has not been determined in a Chinese population. Objective: To provide novel information on the test–retest reliability of thermal QST in the trigeminal and spinal system in healthy Chinese. Methods: Twenty healthy volunteers (10 women and 10 men) participated. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), and heat pain threshold (HPT) were measured at two sites: the surface of the left hand and the left masseter. The testing was performed over three consecutive stimuli trials, three sessions conducted on one day and repeated one week later. Data were analyzed with intra-tester reliability test and four-way analysis of variance (ANOVA) for repeated measures. Results: There was a tendency for the first trial in CDT (p ¼ 0.005), CPT (p ¼ 0.02), and HPT (p50.001) to reflect higher sensitivity than the subsequent two trials. Most variables showed acceptable to excellent reliability and non-significant difference across different trials (ICC: 0.912–0.989), sessions (ICC: 0.791–0.977), and days (ICC: 0.415–0.837). Between-site differences were significant for CDT (p ¼ 0.003) and HPT (p ¼ 0.045) with higher sensitivity at the masseter muscle. There were significant gender differences with higher sensitivity in women for CPT (p ¼ 0.001) and HPT (p ¼ 0.001). Conclusion: Test site and gender affect thermal thresholds substantially. The test–retest reliability of most thermal threshold measures were acceptable for assessing somatosensory function, however, innocuous thresholds appear to be associated with larger variability than noxious thresholds in a Chinese population.
Orofacial pain, quantitative sensory testing, reliability
Introduction In a large epidemiological study, List et al. (1989) reported that 22% of the population suffered from orofacial pain. Aggarwal et al. (2003, 2006) also reported a prevalence of 26% for occasional orofacial pain and 7% for chronic orofacial pain. Diagnosis and treatment of orofacial pain is a common, but also difficult, task for clinicians due to current inabilities to identify the underlying cause and mechanism of pain. The modern concept of a mechanism-based treatment of pain is based on the hypothesis that different clinical signs and symptoms reflect different underlying pathophysiological mechanisms of pain generation (Rolke et al. 2006a). Correspondence: Jinglu Zhang, Orofacial Pain & TMD Research Unit, Institute of Stomatology, Affiliated Hospital of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing 210029, China. Tel: +862586663145. Fax: +862586658322. E-mail: zhangjinglu07@ gmail.com; [email protected]
History Received 6 April 2014 Accepted 7 April 2014 Published online 18 June 2014
Quantitative sensory testing (QST) is a reliable, non-invasive psychophysical test of somatosensory profiles, which has become a useful diagnostic tool for various painful disorders (Hansson 2002). In order to offer comparable test results, the German Research Network on Neuropathic Pain (DFNS) has developed a standardized QST battery that consists of seven tests measuring 13 parameters (Rolke et al. 2006b). Among these parameters, thermal QST parameters are recognized as potentially valuable to assess small-fiber function and provide a diagnostic sensitivity for small-fiber neuropathy from 67 to 100% (Jamal et al. 1987; Tobin et al. 1999; Hansson et al. 2007). A-fiber function is represented by the cold detection threshold (CDT). C-fiber function is represented by the warm detection threshold (WDT) and heat pain threshold (HPT). The relative contribution of C- and A-fiber nociceptors to cold pain threshold (CPT) is less clear (Yarnitsky and Ochoa 1991; Ziegler et al. 1999; Rolke et al. 2006a). Furthermore, thermal QST has been used as an outcome
DOI: 10.3109/08990220.2014.914485
Reliability study of thermal quantitative sensory testing in healthy Chinese
measure in intervention studies (Wasner et al. 2007; Lam et al. 2011; Krumova et al. 2012). QST is not an objective but psychophysical measure and its results depend heavily on the patient. Thus, the consistency of QST data relies on cooperation and attention of the individual being tested as well as several methodological factors. As for any measure to be clinically useful or robust enough for research purposes, it must be both reliable and valid. Given the growing use of thermal QST in profiling patients with orofacial pain and the more recent use of QST as an outcome measure in intervention studies, it is important to establish the robustness of these measures. However, to date reliability relating to thermal QST in the trigeminal region has only been established in Caucasian populations. This may be a concern because there is evidence of significant differences in thermal sensitivity between Caucasian and Chinese populations (Yang et al. 2013). This affects the utility of thermal QST in both clinical practice and research studies of orofacial pain in non-Caucasian populations. The aim of the present study was to assess the intraexaminer test–retest reliability of thermal QST in a cohort of young, healthy adult Chinese and to analyze effects of trial, session, day, gender, and anatomical sites on thermal QST.
Methods Participants Twenty young individuals (10 men and 10 women, mean age 26.8 years, age range from 21 to 35 years) participated in the study. All participants were healthy subjects with no signs or symptoms of pain, hyperalgesia, or allodynia in the head, neck, and face and upper limb region. This was defined as absence of jaw dysfunction and headaches, and absence of subjective pain or soreness of the masticatory muscles. All participants were volunteers recruited from the staff and students of Nanjing Medical University. Exclusion criteria included a history of systemic diseases or mental disorders, presence of any acute or chronic pain conditions in the head, neck, face, and upper limb region, ongoing dental treatment, taking pain medication, antidepressants, or nonsteroidal anti-inflammatory drugs (NSAIDs) in the last month, and current use of caffeine within 24 h of the day of testing. Declaration and informed consent were obtained from all subjects prior to participation. The study was approved by the local ethics committee. Recording technique and experimental protocol Testing was conducted in a quiet, isolated room, free from outside distractions, with an ambient temperature of between 21 and 25 C. All thermal tests were performed by a computer-controlled Peltier-type thermode with a contact area of 16 16 mm2 (Pathway, Medoc, Ramat Yishai, Israel). The temperature of the thermode started from a baseline of 32 C, heated-up or cooled-down at a rate of 1 C/s to the lower bound of 0 C or upper bound of 55 C. Subjects were instructed to press a button on the computer mouse as soon as they perceived the respective thermal sensation of cold, warm, cold pain, or heat pain. The procedure then ended and the temperature returned to baseline at a rate of 1 C/s.
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The tests were applied to the skin overlying the dorsum of the left hand (C7, spinal region) and the skin overlying the left masseter muscle (V3, trigeminal region) in a randomized order. CDT and WDT were measured first, followed by CPT and HPT. Three successive trials with a random inter-stimuli interval (ISI) ranging from 4 to 6 s consisted a recording session. The three trials are normally averaged to provide the threshold; however, in the analyses we tested the reproducibility of each separate trial as a novel aspect. The recording session was performed 3 times at intervals of 10 min. The exact same protocol (three trials, three sessions, two sites) was repeated one week after the first recording. The present study focused on the intra-examiner test–retest reliability and included a single, qualified dentist with experience in orofacial pain and previous training in psychophysical examinations. This examiner was specifically trained and calibrated according to the DFNS examination protocol by one of the authors who was officially trained and calibrated by the DFNS team. The verbal instructions given to the participants before the experiments were translated from the DFNS protocol. The participants also performed a practice session in which the thermode was attached to the forearm until they were familiarized with the measurement procedure and the equipment. The participants were unable to watch the computer screen at any time during the test procedures. Statistical analysis All data were normalized with decimal logarithm and 1 was added to avoid negative log values. Descriptive statistics were used to summarize all measurements. The mean values and standard deviation of CDT, WDT, CPT, and HPT in each gender and each test site were calculated over three trials, three sessions, and two days. The intraclass correlation coefficient (ICC) (two-way mixed model, consistency type) and the 95% confidence interval (95% CI) were used to quantify the test–retest reliability of measurement over the three trials, three sessions, and two days, respectively, across the range of sites and subjects. Theoretically, ICC varies from 0 to 1 and a commonly accepted rule of thumb for describing reproducibility using ICC is above 0.6. ICC50.4 is considered poor, 0.4–0.59: fair, 0.6–0.75: good, and 40.75: excellent agreement. The mean and the standard error of the mean (SEM) were also used to provide an absolute index of the reliability within individual subjects (Weir 2005). The design of the experiment also corresponded to a repeated measurements framework. Four-way analysis of variance (ANOVA) with repeated measures was performed to assess the effects of the within-subject factors of trial, session, day, and site and between-subject factor of gender. Two-tailed tests with a significance level of 5% were used throughout. All statistical calculations were performed by using the Statistical Package for Social Sciences version 16 (SPSS, IBM, Armonk, NY, USA).
Results All subjects completed the study. The absolute values of all variables CDT, WDT, CPT, and HPT for the two genders at
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Table I. The absolute means and SDs for all thermal threshold variables by different days, sessions, and trials in different gender at two test sites. Site (left hand) Gender Men
Session
Trial
CDT ( C)
WDT ( C)
CPT ( C)
HPT ( C)
CDT ( C)
WDT ( C)
CPT ( C)
HPT ( C)
1
1
1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3
29.7 ± 2.0 30.1 ± 1.7 30.6 ± 1.2 30.3 ± 1.5 30.5 ± 1.1 30.7 ± 1.1 30.3 ± 1.3 30.6 ± 1.7 30.4 ± 1.5 29.3 ± 2.2 30.1 ± 1.8 30.4 ± 1.9 30.6 ± 1.1 30.6 ± 1.5 30.6 ± 1.7 30.0 ± 1.1 30.3 ± 1.0 30.2 ± 1.2
34.0 ± 0.8 34.1 ± 1.0 33.8 ± 1.2 34.1 ± 0.7 33.5 ± 0.9 34.1 ± 0.9 33.9 ± 0.9 33.7 ± 1.1 34.0 ± 1.0 34.0 ± 1.3 33.9 ± 0.9 34.2 ± 1.3 34.1 ± 1.6 34.1 ± 1.9 34.1 ± 2 34.1 ± 1.1 34.2 ± 1.5 34.0 ± 1.5
11.0 ± 10.1 10.3 ± 9.3 10.6 ± 9.3 11.8 ± 9.9 10.6 ± 8.5 10.2 ± 9.0 13.0 ± 9.6 11.6 ± 8.9 11.0 ± 8.5 12.7 ± 8.1 12.5 ± 7.3 11.8 ± 7.2 13.2 ± 8.8 12.6 ± 7.7 10.7 ± 7.5 12.6 ± 9.1 11.6 ± 8.3 10.7 ± 7.9
42.7 ± 3.0 43.5 ± 3.1 44.1 ± 3.7 43.3 ± 3.1 45.0 ± 2.5 45.4 ± 3.3 43.5 ± 3.3 44.8 ± 3.7 45.6 ± 3.5 42.5 ± 1.6 43.5 ± 1.5 44.1 ± 2.5 43.6 ± 2.6 44.7 ± 3.0 44.9 ± 3.1 44.5 ± 2.2 45.2 ± 2.0 45.7 ± 2.3
30.4 ± 1.4 30.7 ± 0.9 30.9 ± 0.9 30.7 ± 1.0 30.7 ± 1.4 30.9 ± 1.0 30.5 ± 1.1 30.7 ± 1.1 30.7 ± 1.1 30.6 ± 0.5 30.8 ± 0.4 30.9 ± 0.6 30.7 ± 0.9 31.0 ± 1.0 30.9 ± 1.3 30.6 ± 0.8 30.7 ± 0.8 30.9 ± 0.8
34.3 ± 1.3 34.3 ± 1.0 34.2 ± 0.8 33.9 ± 1.1 34.0 ± 0.7 33.8 ± 0.6 34.0 ± 0.9 34.1 ± 0.9 33.9 ± 0.8 34.1 ± 1.0 33.8 ± 1.0 34.1 ± 1.0 34.0 ± 1.1 34.0 ± 1.2 34.0 ± 1.0 34.2 ± 0.9 34.2 ± 1.3 34.2 ± 1.2
6.9 ± 10.0 7.9 ± 9.8 10.0 ± 11.7 9.2 ± 11.0 8.1 ± 11.0 7.6 ± 10.0 7.5 ± 9.7 6.4 ± 9.2 6.6 ± 8.9 10.7 ± 10.4 9.6 ± 9.6 9.0 ± 9.5 10.1 ± 10.6 9.4 ± 9.9 8.9 ± 9.7 8.7 ± 8.8 7.7 ± 9.0 7.8 ± 7.9
42.4 ± 2.7 42.5 ± 3.0 43.5 ± 3.4 42.3 ± 3.9 43.8 ± 4.0 44.3 ± 4.2 44.0 ± 3.2 44.7 ± 3.1 44.9 ± 3.5 42.3 ± 2.4 43.4 ± 2.9 43.8 ± 3.1 42.9 ± 2.9 43.6 ± 2.9 44.2 ± 3.0 44.2 ± 2.2 44.5 ± 2.3 45.2 ± 2.7
1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3
30.1 ± 2.0 30.1 ± 1.5 30.6 ± 0.8 30.7 ± 0.7 30.8 ± 0.7 31.0 ± 0.6 30.5 ± 1.2 30.7 ± 1.4 30.6 ± 1.1 29 ± 2.3 29.4 ± 2.2 29.9 ± 1.7 30.0 ± 2.0 30.0 ± 1.8 30.3 ± 1.5 29.9 ± 1.9 30.4 ± 1.1 30.5 ± 1.2
33.6 ± 0.6 33.6 ± 0.7 33.8 ± 0.8 33.2 ± 0.6 33.6 ± 0.7 33.7 ± 0.8 33.9 ± 1.0 33.9 ± 1.2 34.1 ± 1.3 34.3 ± 1.2 34.0 ± 1.3 34.0 ± 1.3 33.6 ± 1.0 33.8 ± 0.9 33.9 ± 0.8 33.7 ± 1.1 34.2 ± 1.5 34.3 ± 1.8
20.4 ± 8.6 19.9 ± 7.8 19.8 ± 7.7 22.5 ± 4.3 19.4 ± 5.7 18.7 ± 6.1 21.0 ± 6.3 18.9 ± 6.3 17.4 ± 7.3 24.0 ± 6.1 22.6 ± 5.7 21.3 ± 5.6 23.7 ± 3.8 21.9 ± 4.8 20.9 ± 6.1 22.1 ± 8.1 20.8 ± 7.4 20.5 ± 7.7
38.3 ± 2.7 38.5 ± 2.6 40.3 ± 2.8 41.1 ± 1.7 43.3 ± 2.2 44.3 ± 1.9 41.7 ± 2.8 43.8 ± 2.2 45.0 ± 2.3 40.0 ± 3.0 41.3 ± 3.5 41.8 ± 6.6 40.4 ± 3.1 42.1 ± 3.5 42.4 ± 3.5 41.6 ± 3.5 42.8 ± 3.7 43.5 ± 3.1
30.8 ± 1.1 30.7 ± 1.0 31.2 ± 0.4 30.9 ± 0.7 30.8 ± 1.0 31.1 ± 0.5 30.9 ± 0.7 30.9 ± 0.6 31 ± 1.0 30.4 ± 1.0 31.0 ± 0.5 31.0 ± 0.6 30.8 ± 0.6 31.1 ± 0.4 31.2 ± 0.3 30.6 ± 1.1 31.1 ± 0.5 31.1 ± 0.6
34.0 ± 0.7 33.9 ± 0.9 33.9 ± 0.9 33.7 ± 0.5 33.6 ± 0.7 33.6 ± 0.6 33.7 ± 0.8 33.7 ± 1.1 33.7 ± 1.0 33.9 ± 1.0 33.9 ± 0.9 33.8 ± 0.7 33.8 ± 1.1 33.6 ± 0.8 33.7 ± 0.7 33.7 ± 0.7 33.7 ± 0.8 33.9 ± 1.0
24.8 ± 5.9 23.5 ± 6.2 23.1 ± 5.7 24.1 ± 6.5 22.4 ± 7 21.8 ± 5.9 23.3 ± 8.1 21.1 ± 8.5 19.6 ± 8.3 26.6 ± 5.4 25.8 ± 5.0 24.9 ± 5.8 26.9 ± 4.1 25.6 ± 4.9 24.1 ± 5.2 25.6 ± 6.0 24.1 ± 6.3 23.4 ± 5.5
37.9 ± 2.6 38.8 ± 2.7 39.4 ± 2.9 39.6 ± 3.7 40.6 ± 3.3 41.6 ± 3.8 40.1 ± 3.7 41.4 ± 3.7 42.6 ± 3.8 38.8 ± 3.0 39.3 ± 3.2 40.1 ± 3.5 39.0 ± 2.7 40.2 ± 3.5 41.0 ± 3.7 40.0 ± 3.4 41.0 ± 3.8 42.1 ± 4.2
3 2
1 2 3
Women
1
1 2 3
2
1 2 3
Site (left masseter)
Day
2
the two test sites over three trials, three sessions, and two days (one week apart) are presented as means and SDs in Table I. Most of the thermal thresholds were stable over the three sessions and two days while some variables, for example, CDT, CPT, and HPT, showed some difference between sites or gender.
test–retest reliabilities in the fair range. Table III lists the mean and SEM of all thermal thresholds for the two sites. In general, the SEMs indicated low variability. Moreover, the test–retest reliability data were supplemented by ANOVAs with repeated measurement to further characterize the time effects (trials, sessions, and days).
The intra-examiner test–retest reliability for all variables over different time intervals
Test of within-subject and between-subject effects for all variables in different gender at two sites over different time intervals
Table II lists the ICC values and 95% CI of all thermal thresholds over the three trials, three sessions, and two days for the two sites. The test–retest reliability of all thermal thresholds (CDT, WDT, CPT, and HPT) showed excellent agreement and the ICC values of all variables were 1 between different trials (Table II). The ICC values of all thermal thresholds at two test sites also showed excellent agreement (ranged from 0.791 to 0.977) over the different sessions. However, over different days, some variables of thermal pain threshold, including CPT and HPT, were associated with test–retest reliabilities that ranged from good to excellent (ranged from 0.611 to 0.837). Other variables of thermal detection threshold including CDT (ICChand ¼ 0.589, ICCmasseter ¼ 0.566) and WDT (ICChand ¼ 0.415, ICCmasseter ¼ 0.569) were associated with
The four-way ANOVA showed significant main effects of trials for CDT (p50.01), CPT (p ¼ 0.02), and HPT (p50.01) but not for WDT (p ¼ 0.503). Generally, the first trial for CDT, CPT, and HPT tended to reflect higher sensitivity (higher thresholds for CDT and CPT, lower thresholds for HPT) compared with the subsequent two trials (Table IV). There were no significant main effects of session for CDT (p ¼ 0.437), WDT (p ¼ 0.744), or CPT (p ¼ 0.318) whereas the HPT varied across sessions (p50.01; Table IV) with lower values in the first session compared to the last session. There were no significant main effects of days for CDT (p ¼ 0.398), WDT (p ¼ 0.223), CPT (p ¼ 0.264), or HPT (p ¼ 0.943) between the two weeks (Table IV).
Reliability study of thermal quantitative sensory testing in healthy Chinese
DOI: 10.3109/08990220.2014.914485
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Table II. Test–retest reliability measurements for all thermal threshold variables at two sites over three trials, three sessions, and two days.
Site
Variables
ICC (95% CI) across different trials
ICC (95% CI) across different sessions
ICC (95% CI) across different days
Left hand
CDT CPT HPT WDT
0.932 0.981 0.949 0.913
(0.907–0.950) (0.974–0.986) (0.931–0.963) (0.882–0.937)
0.848 (0.795–0.890) 0.964 (0.951–0.974) 0.791 (0.716–0.848) 0.8 (0.729–0.855)
0.589 0.752 0.611 0.415
(0.448–0.693) (0.667–0.815) (0.439–0.721) (0.214–0.564)
Left masseter
CDT CPT HPT WDT
0.912 0.989 0.976 0.919
(0.880–0.936) (0.985–0.992) (0.967–0.982) (0.890–0.941)
0.89 (0.851–0.920) 0.977 (0.968–0.983) 0.902 (0.867–0.929) 0.875 (0.830–0.909)
0.566 0.837 0.646 0.569
(0.418–0.677) (0.781–0.879) (0.526–0.737) (0.421–0.678)
The values were reported as intraclass correlation coefficient (ICC) and 95% confidence interval (95% CI) for all variables over three different sessions at the different day and over two different days. ICC50.4 is considered poor, 0.4–0.59: fair, 0.6–0.75: good, and 40.75: excellent agreement. Table III. The mean and SEM of all thermal thresholds across different trials, sessions, and days for the two sites.
Site Left hand
CDT WDT CPT HPT Time interval Mean SEM Mean SEM Mean SEM Mean SEM Trial 1 2 3 Session 1 2 3 Day 1 2 Total
Left Trial masseter 1 2 3 Session 1 2 3 Day 1 2 Total
30.02 0.15 33.87 0.09 17.33 0.83 41.93 0.29 30.30 0.14 33.89 0.10 16.05 0.77 43.19 0.30 30.48 0.12 33.99 0.11 15.28 0.78 43.91 0.33 29.95 0.16 33.92 0.09 16.40 0.83 41.70 0.34 30.48 0.12 33.82 0.10 16.34 0.77 43.36 0.28 30.37 0.12 34.00 0.11 15.93 0.80 43.96 0.28
Table IV. Test of within-subject and between-subject effects for CDT, WDT, CPT, and HPT in different gender at two sites over three trials, three sessions, and two days (one week apart) by four-way ANOVAs with repeated measures. CDT F
CPT p
F
Site 11.936 0.003* 2.12 Day 1.711 0.398 1.327 Session 0.641 0.437 1.167 Trial 9.14 0.005* 6.26 Gender 0.021 0.887 16.296
HPT p
F
WDT p
F
0.163 4.654 0.045 0 0.264 0.005 0.943 1.592 0.318 15.953 0.001* 0.168 0.02* 94.086 0.000* 0.619 0.001* 16.962 0.001* 0.663
p 0.994 0.223 0.744 0.503 0.426
*Indicates significant difference (p50.05). 30.45 0.10 33.80 0.07 15.44 0.66 42.99 0.26 30.07 0.12 34.03 0.10 17.00 0.63 43.02 0.26 30.26 0.08 33.92 0.06 16.22 0.46 43.01 0.18
Discussion 30.66 0.08 33.94 0.09 17.03 1.05 41.11 0.33 30.85 0.08 33.89 0.09 15.96 1.02 41.95 0.33 30.98 0.07 33.90 0.08 15.56 0.98 42.73 0.35 30.77 0.08 34.01 0.08 16.89 1.02 41.01 0.32 30.91 0.08 33.81 0.08 16.50 1.01 41.90 0.35 30.81 0.08 33.91 0.09 15.16 1.01 42.89 0.33 30.81 0.07 33.89 0.06 15.21 0.83 41.90 0.29 30.85 0.06 33.93 0.07 17.16 0.82 41.97 0.27 30.83 0.04 33.91 0.05 16.18 0.59 41.93 0.20
Site effects There were significant site differences for CDT as shown in Table II. The multiple comparison test (Bonferroni) revealed the CDT at the left hand was lower (lower sensitivity) than at the left masseter (p ¼ 0.003). Furthermore, a significant site effect was observed for HPT, with higher (lower sensitivity) values at the left hand than at the left masseter (p ¼ 0.045) (Table II). Subject and gender effects There was no significant age difference between men and women (p ¼ 0.191). There were significant gender differences with lower thresholds in men (lower sensitivity) than in women for CPT (p ¼ 0.001) and higher thresholds in men (lower sensitivity) than in women for HPT (p ¼ 0.001) (Table II).
The present study provided new aspects of the test–retest reliability of thermal QST in the trigeminal and spinal system in healthy Chinese. CDT, WDT, CPT, and HPT were measured at two sites: the surface of the left hand and left masseter for 20 healthy volunteers (10 women and 10 men). The testing was performed over three consecutive stimuli trials, three sessions conducted on one day and repeated one week later. The results show that the test–retest reliability of most thermal threshold measures was acceptable to excellent for assessing somatosensory function, however, test site and gender affect thermal thresholds substantially. To our knowledge the present study, for the first time, investigated these important aspects of the test–retest reliability of thermal QST in the trigeminal and spinal system in a non-Caucasian population. Absolute data of thermal QST Thermal QST are recognized to be potentially valuable to assess small-fiber function, but their widespread use has been discouraged because reference values from different studies are inhomogeneous (Magerl et al. 2010). The mean values of our absolute thermal QST data in a Chinese population compare well with prior studies for thermal detection and pain thresholds (Lang et al. 2006; Wasner and Brock 2008). Yang et al. (2013) observed significant differences in thermal sensitivity in the trigeminal region between a Caucasian and Chinese population.
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Wide ranges for thermal QST data in individual cases were seen, as also occurred in the study by Rolke et al. (2006a) on 180 healthy volunteers as well as former studies (Yarnitsky et al. 1995; Klauenberg et al. 2008). The relatively large variability indicates that the references of these QST measures are wide, affecting clinical utilization. This calls for adequate reference groups, standardization of QST methodologies and test protocols, and also the need to establish appropriate measures of test–retest reliability. There are several possible explanations for the variability of QST measures. One obvious explanation in addition to methodological differences may be that QST is a psychophysical method which is strongly influenced by the interaction and communication between the test subject and the examiner, and furthermore, that the QST outcome depends on the motor abilities and attention of the patient (Hansson et al. 2007). Mental factors may also influence individual thermal detection and pain thresholds in orofacial pain patients, for example, anxiety, former pain experiences, and coping strategies. All these factors need to be considered in order to interpret the QST outcome correctly. The present study provides a basis to implement thermal QST in a Chinese population. Gender and site differences in somatosensory function The reported results are similar to several other studies that found women more sensitive than men for many thermal QST parameters (Riley et al. 1998). However, the present findings indicate that gender differences were present only for pain thresholds including CPT and HPT. Since thermal detection thresholds were independent of gender, the differences in pain thresholds are unlikely to be due to peripheral factors such as innervation density, and may be attributed to different central processing (Rollman and Lautenbacher 2001; Sarlani et al. 2003). As it has been reported that women are more sensitive to thermal stimuli (Hansson et al. 2007; Blankenburg et al. 2011), a thorough understanding of developmental and sexrelated differences in pain perception is important. LeResche et al. used epidemiological studies for pain detection in children and adolescents and found that marked sex differences arising around puberty, with girls reporting greater and more frequent pain than boys (LeResche et al. 2005; KronerHerwig et al. 2007). At the same time Riley et al. found marked sex differences are present in adults with females more sensitive to thermal stimuli than males (Riley et al. 1998; Rolke et al. 2006a; Blankenburg et al. 2010). The results of our study are in accordance with the former studies. The present study also demonstrated that absolute threshold values varied between two anatomical sites and our results are in accordance with former studies (Rolke et al. 2006a). Sensitivity was higher on the face than on the hand for CDT and HPT. We suspect that it may be due to the decreased distance to the central nervous system (CNS) when comparing the face with the hand. Our results suggest that to determine whether somatosensory changes have occurred, it is important to consider the site being tested.
Somatosens Mot Res, 2014; 31(4): 198–203
Time effect on the reliability of thermal QST parameters We have analyzed both the trial, session, and week effects on the reliability of thermal QST. A one-week interval between assessments was used as it might be a reasonable time interval relevant for clinical studies or patient follow-up. While test– retest reliability of repeated assessments over consecutive days has been established in former studies, few studies have assessed repeated within-session and trial-to-trial assessment (Cathcart and Pritchard 2006; Pigg et al. 2010; Moloney et al. 2011). Interestingly and importantly, we found that the first trial for CDT, CPT, and HPT tended to reflect higher sensitivity compared with the subsequent two trials. This result may be explained as habituation which is described as a behavioral response decrement that results from repeated stimulation (Thompson and Spencer 1966). In thermal QST, the application of repetitive thermal stimuli on a fixed location could lead to increased thresholds and less sensitivity. The habituation may be due to the increasing fatigue of A- and C-fiber nociceptors (Greffrath et al. 2007). The reliability of all thermal thresholds at the two test sites showed excellent agreement (ranged from 0.791 to 0.977) over different sessions and trials. However, over different days, some variables of thermal pain threshold, including CPT and HPT, showed good to excellent reliabilities; while CDT and WDT were only fair. Moreover, we used the SEM to provide an absolute index of reliability which is not affected by the between-subject variability as is the ICC. The result showed the SEM values were relatively small for all thermal thresholds. In our study, there were no significant main effects of session for CDT, WDT, or CPT whereas HPT varied across sessions with lower values in the first session compared to the last session. The poorer reproducibility between sessions for HPT implies that HPT assessment is associated with greater uncertainty and therefore that clinical differences may be more difficult to detect. In contrast, others have reported better HPT reliability on the facial skin (Geber et al. 2011; Wylde et al. 2011) although considerable within-subject variability in HPT has also been found in previous studies (Geber et al. 2011; Moloney et al. 2011, 2012). In our study, HPT reliability varied greatly between different sessions. The reasons for this variability are unknown but could reflect variations in heat pain sensitive afferent fiber density or biophysical properties. In conclusion, this study’s main findings are that the test– retest reliability of thermal QST parameters is acceptable to excellent and that the DFNS protocol can be applied in a healthy Chinese population. This shows that thermal QST is feasible and repeatable for use in future applications such as the establishment of normative values and possibly for mechanism-based profiling of orofacial pain. However, the limitation of this study may be that, due to the relatively small sample size, inclusion of healthy controls and the applied fixed time intervals, the power could have been insufficient to allow detection of more subtle differences. Future studies will be needed to record from larger groups of matched subjects and orofacial pain patients to highlight possible variation over different time intervals.
DOI: 10.3109/08990220.2014.914485
Reliability study of thermal quantitative sensory testing in healthy Chinese
Declaration of interest The authors report no conflicts of interest. This work was supported by National Natural Science Foundation of China (Grant Nos. 30973361 and 81170981); Jiangsu Government scholarship for overseas study (Grant No. JS-2009-083); PhD Programs Foundation of Ministry of Education of China (Grant No. 20113234110003); and the Priority Academic Program Development of Jiangsu Higher Education Institutions. A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institute (Grant No. 2014-37).
References Aggarwal VR, Macfarlane TV, Macfarlane GJ. 2003. Why is pain more common amongst people living in areas of low socio-economic status? A population-based cross-sectional study. Br Dent J 194: 383–387; discussion 380. Aggarwal VR, McBeth J, Zakrzewska JM, Lunt M, Macfarlane GJ. 2006. The epidemiology of chronic syndromes that are frequently unexplained: Do they have common associated factors? Int J Epidemiol 35: 468–476. Blankenburg M, Boekens H, Hechler T, Maier C, Krumova E, Scherens A, Magerl W, Aksu F, Zernikow B. 2010. Reference values for quantitative sensory testing in children and adolescents: Developmental and gender differences of somatosensory perception. Pain 149:76–88. Blankenburg M, Meyer D, Hirschfeld G, Kraemer N, Hechler T, Aksu F, Krumova EK, Magerl W, Maier C, Zernikow B. 2011. Developmental and sex differences in somatosensory perception—A systematic comparison of 7- versus 14-year-olds using quantitative sensory testing. Pain 152:2625–2631. Cathcart S, Pritchard D. 2006. Reliability of pain threshold measurement in young adults. J Headache Pain 7:21–26. Geber C, Klein T, Azad S, Birklein F, Gierthmuhlen J, Huge V, Lauchart M, Nitzsche D, Stengel M, Valet M, et al. 2011. Test–retest and interobserver reliability of quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain (DFNS): A multi-centre study. Pain 152:548–556. Greffrath W, Baumgartner U, Treede RD. 2007. Peripheral and central components of habituation of heat pain perception and evoked potentials in humans. Pain 132:301–311. Hansson P. 2002. Neuropathic pain: Clinical characteristics and diagnostic workup. Eur J Pain 6(Suppl. A):47–50. Hansson P, Backonja M, Bouhassira D. 2007. Usefulness and limitations of quantitative sensory testing: Clinical and research application in neuropathic pain states. Pain 129:256–259. Jamal GA, Hansen S, Weir AI, Ballantyne JP. 1987. The neurophysiologic investigation of small fiber neuropathies. Muscle Nerve 10: 537–545. Klauenberg S, Maier C, Assion HJ, Hoffmann A, Krumova EK, Magerl W, Scherens A, Treede RD, Juckel G. 2008. Depression and changed pain perception: Hints for a central disinhibition mechanism. Pain 140:332–343. Kroner-Herwig B, Heinrich M, Morris L. 2007. Headache in German children and adolescents: A population-based epidemiological study. Cephalalgia 27:519–527. Krumova EK, Zeller M, Westermann A, Maier C. 2012. Lidocaine patch (5%) produces a selective, but incomplete block of Adelta and C fibers. Pain 153:273–280. Lam VY, Wallace M, Schulteis G. 2011. Effects of lidocaine patch on intradermal capsaicin-induced pain: A double-blind, controlled trial. J Pain 12:323–330.
203
Lang PM, Schober GM, Rolke R, Wagner S, Hilge R, Offenbacher M, Treede RD, Hoffmann U, Irnich D. 2006. Sensory neuropathy and signs of central sensitization in patients with peripheral arterial disease. Pain 124:190–200. LeResche L, Mancl LA, Drangsholt MT, Saunders K, Korff MV. 2005. Relationship of pain and symptoms to pubertal development in adolescents. Pain 118:201–209. List T, Helkimo M, Falk G. 1989. Reliability and validity of a pressure threshold meter in recording tenderness in the masseter muscle and the anterior temporalis muscle. Cranio 7:223–229. Magerl W, Krumova EK, Baron R, Tolle T, Treede RD, Maier C. 2010. Reference data for quantitative sensory testing (QST): Refined stratification for age and a novel method for statistical comparison of group data. Pain 151:598–605. Moloney NA, Hall TM, O’Sullivan TC, Doody CM. 2011. Reliability of thermal quantitative sensory testing of the hand in a cohort of young, healthy adults. Muscle Nerve 44:547–552. Moloney NA, Hall TM, Doody CM. 2012. Reliability of thermal quantitative sensory testing: A systematic review. J Rehabil Res Dev 49:191–207. Pigg M, Baad-Hansen L, Svensson P, Drangsholt M, List T. 2010. Reliability of intraoral quantitative sensory testing (QST). Pain 148: 220–226. Riley 3rd JL, Robinson ME, Wise EA, Myers CD, Fillingim RB. 1998. Sex differences in the perception of noxious experimental stimuli: A meta-analysis. Pain 74:181–187. Rolke R, Baron R, Maier C, Tolle TR, Treede RD, Beyer A, Binder A, Birbaumer N, Birklein F, Botefur IC, et al. 2006a. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values. Pain 123: 231–243. Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein F, Treede RD. 2006b. Quantitative sensory testing: A comprehensive protocol for clinical trials. Eur J Pain 10:77–88. Rollman GB, Lautenbacher S. 2001. Sex differences in musculoskeletal pain. Clin J Pain 17:20–24. Sarlani E, Farooq N, Greenspan JD. 2003. Gender and laterality differences in thermosensation throughout the perceptible range. Pain 106:9–18. Thompson RF, Spencer WA. 1966. Habituation: A model phenomenon for the study of neuronal substrates of behavior. Psychol Rev 73: 16–43. Tobin K, Giuliani MJ, Lacomis D. 1999. Comparison of different modalities for detection of small fiber neuropathy. Clin Neurophysiol 110:1909–1912. Wasner G, Naleschinski D, Baron R. 2007. A role for peripheral afferents in the pathophysiology and treatment of at-level neuropathic pain in spinal cord injury? A case report. Pain 131:219–225. Wasner GL, Brock JA. 2008. Determinants of thermal pain thresholds in normal subjects. Clin Neurophysiol 119:2389–2395. Weir JP. 2005. Quantifying test–retest reliability using the intraclass correlation coefficient and the SEM. J Strength Cond Res 19:231–240. Wylde V, Palmer S, Learmonth ID, Dieppe P. 2011. Test–retest reliability of Quantitative Sensory Testing in knee osteoarthritis and healthy participants. Osteoarthritis Cartilage 19:655–658. Yang G, Luo Y, Baad-Hansen L, Wang K, Arendt-Nielsen L, Xie QF, Svensson P. 2013. Ethnic differences in oro-facial somatosensory profiles—Quantitative sensory testing in Chinese and Danes. J Oral Rehabil 40:844–853. Yarnitsky D, Ochoa JL. 1991. Differential effect of compressionischaemia block on warm sensation and heat-induced pain. Brain 114(Pt 2):907–913. Yarnitsky D, Sprecher E, Zaslansky R, Hemli JA. 1995. Heat pain thresholds: Normative data and repeatability. Pain 60:329–332. Ziegler EA, Magerl W, Meyer RA, Treede RD. 1999. Secondary hyperalgesia to punctate mechanical stimuli. Central sensitization to A-fibre nociceptor input. Brain 122(Pt 12):2245–2257.
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ORIGINAL ARTICLE
Reliability study of thermal quantitative sensory testing in healthy Chinese Ruixia Wang1, Linlin Cui1, Weina Zhou1, Chen Wang1, Jinglu Zhang1, Kelun Wang2,3, & Peter Svensson4 1
Orofacial Pain & TMD Research Unit, Institute of Stomatology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China, Center for Sensory–Motor Interaction (SMI), Aalborg University, Aalborg, Denmark, 3Stomatological School and Hospital, Nanjing Medical University, Nanjing, China, and 4Section of Clinical Oral Physiology, School of Dentistry, Aarhus University, Aarhus, Denmark
2
Abstract
Keywords
Background: Test–retest reliability is important to establish for any diagnostic tool. The reliability of quantitative sensory testing (QST) in the trigeminal region has recently been described in Caucasians as well as differences in absolute thresholds and responses between Caucasians and Chinese. However, the test–retest reliability has not been determined in a Chinese population. Objective: To provide novel information on the test–retest reliability of thermal QST in the trigeminal and spinal system in healthy Chinese. Methods: Twenty healthy volunteers (10 women and 10 men) participated. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), and heat pain threshold (HPT) were measured at two sites: the surface of the left hand and the left masseter. The testing was performed over three consecutive stimuli trials, three sessions conducted on one day and repeated one week later. Data were analyzed with intra-tester reliability test and four-way analysis of variance (ANOVA) for repeated measures. Results: There was a tendency for the first trial in CDT (p ¼ 0.005), CPT (p ¼ 0.02), and HPT (p50.001) to reflect higher sensitivity than the subsequent two trials. Most variables showed acceptable to excellent reliability and non-significant difference across different trials (ICC: 0.912–0.989), sessions (ICC: 0.791–0.977), and days (ICC: 0.415–0.837). Between-site differences were significant for CDT (p ¼ 0.003) and HPT (p ¼ 0.045) with higher sensitivity at the masseter muscle. There were significant gender differences with higher sensitivity in women for CPT (p ¼ 0.001) and HPT (p ¼ 0.001). Conclusion: Test site and gender affect thermal thresholds substantially. The test–retest reliability of most thermal threshold measures were acceptable for assessing somatosensory function, however, innocuous thresholds appear to be associated with larger variability than noxious thresholds in a Chinese population.
Orofacial pain, quantitative sensory testing, reliability
Introduction In a large epidemiological study, List et al. (1989) reported that 22% of the population suffered from orofacial pain. Aggarwal et al. (2003, 2006) also reported a prevalence of 26% for occasional orofacial pain and 7% for chronic orofacial pain. Diagnosis and treatment of orofacial pain is a common, but also difficult, task for clinicians due to current inabilities to identify the underlying cause and mechanism of pain. The modern concept of a mechanism-based treatment of pain is based on the hypothesis that different clinical signs and symptoms reflect different underlying pathophysiological mechanisms of pain generation (Rolke et al. 2006a). Correspondence: Jinglu Zhang, Orofacial Pain & TMD Research Unit, Institute of Stomatology, Affiliated Hospital of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing 210029, China. Tel: +862586663145. Fax: +862586658322. E-mail: zhangjinglu07@ gmail.com; [email protected]
History Received 6 April 2014 Accepted 7 April 2014 Published online 18 June 2014
Quantitative sensory testing (QST) is a reliable, non-invasive psychophysical test of somatosensory profiles, which has become a useful diagnostic tool for various painful disorders (Hansson 2002). In order to offer comparable test results, the German Research Network on Neuropathic Pain (DFNS) has developed a standardized QST battery that consists of seven tests measuring 13 parameters (Rolke et al. 2006b). Among these parameters, thermal QST parameters are recognized as potentially valuable to assess small-fiber function and provide a diagnostic sensitivity for small-fiber neuropathy from 67 to 100% (Jamal et al. 1987; Tobin et al. 1999; Hansson et al. 2007). A-fiber function is represented by the cold detection threshold (CDT). C-fiber function is represented by the warm detection threshold (WDT) and heat pain threshold (HPT). The relative contribution of C- and A-fiber nociceptors to cold pain threshold (CPT) is less clear (Yarnitsky and Ochoa 1991; Ziegler et al. 1999; Rolke et al. 2006a). Furthermore, thermal QST has been used as an outcome
DOI: 10.3109/08990220.2014.914485
Reliability study of thermal quantitative sensory testing in healthy Chinese
measure in intervention studies (Wasner et al. 2007; Lam et al. 2011; Krumova et al. 2012). QST is not an objective but psychophysical measure and its results depend heavily on the patient. Thus, the consistency of QST data relies on cooperation and attention of the individual being tested as well as several methodological factors. As for any measure to be clinically useful or robust enough for research purposes, it must be both reliable and valid. Given the growing use of thermal QST in profiling patients with orofacial pain and the more recent use of QST as an outcome measure in intervention studies, it is important to establish the robustness of these measures. However, to date reliability relating to thermal QST in the trigeminal region has only been established in Caucasian populations. This may be a concern because there is evidence of significant differences in thermal sensitivity between Caucasian and Chinese populations (Yang et al. 2013). This affects the utility of thermal QST in both clinical practice and research studies of orofacial pain in non-Caucasian populations. The aim of the present study was to assess the intraexaminer test–retest reliability of thermal QST in a cohort of young, healthy adult Chinese and to analyze effects of trial, session, day, gender, and anatomical sites on thermal QST.
Methods Participants Twenty young individuals (10 men and 10 women, mean age 26.8 years, age range from 21 to 35 years) participated in the study. All participants were healthy subjects with no signs or symptoms of pain, hyperalgesia, or allodynia in the head, neck, and face and upper limb region. This was defined as absence of jaw dysfunction and headaches, and absence of subjective pain or soreness of the masticatory muscles. All participants were volunteers recruited from the staff and students of Nanjing Medical University. Exclusion criteria included a history of systemic diseases or mental disorders, presence of any acute or chronic pain conditions in the head, neck, face, and upper limb region, ongoing dental treatment, taking pain medication, antidepressants, or nonsteroidal anti-inflammatory drugs (NSAIDs) in the last month, and current use of caffeine within 24 h of the day of testing. Declaration and informed consent were obtained from all subjects prior to participation. The study was approved by the local ethics committee. Recording technique and experimental protocol Testing was conducted in a quiet, isolated room, free from outside distractions, with an ambient temperature of between 21 and 25 C. All thermal tests were performed by a computer-controlled Peltier-type thermode with a contact area of 16 16 mm2 (Pathway, Medoc, Ramat Yishai, Israel). The temperature of the thermode started from a baseline of 32 C, heated-up or cooled-down at a rate of 1 C/s to the lower bound of 0 C or upper bound of 55 C. Subjects were instructed to press a button on the computer mouse as soon as they perceived the respective thermal sensation of cold, warm, cold pain, or heat pain. The procedure then ended and the temperature returned to baseline at a rate of 1 C/s.
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The tests were applied to the skin overlying the dorsum of the left hand (C7, spinal region) and the skin overlying the left masseter muscle (V3, trigeminal region) in a randomized order. CDT and WDT were measured first, followed by CPT and HPT. Three successive trials with a random inter-stimuli interval (ISI) ranging from 4 to 6 s consisted a recording session. The three trials are normally averaged to provide the threshold; however, in the analyses we tested the reproducibility of each separate trial as a novel aspect. The recording session was performed 3 times at intervals of 10 min. The exact same protocol (three trials, three sessions, two sites) was repeated one week after the first recording. The present study focused on the intra-examiner test–retest reliability and included a single, qualified dentist with experience in orofacial pain and previous training in psychophysical examinations. This examiner was specifically trained and calibrated according to the DFNS examination protocol by one of the authors who was officially trained and calibrated by the DFNS team. The verbal instructions given to the participants before the experiments were translated from the DFNS protocol. The participants also performed a practice session in which the thermode was attached to the forearm until they were familiarized with the measurement procedure and the equipment. The participants were unable to watch the computer screen at any time during the test procedures. Statistical analysis All data were normalized with decimal logarithm and 1 was added to avoid negative log values. Descriptive statistics were used to summarize all measurements. The mean values and standard deviation of CDT, WDT, CPT, and HPT in each gender and each test site were calculated over three trials, three sessions, and two days. The intraclass correlation coefficient (ICC) (two-way mixed model, consistency type) and the 95% confidence interval (95% CI) were used to quantify the test–retest reliability of measurement over the three trials, three sessions, and two days, respectively, across the range of sites and subjects. Theoretically, ICC varies from 0 to 1 and a commonly accepted rule of thumb for describing reproducibility using ICC is above 0.6. ICC50.4 is considered poor, 0.4–0.59: fair, 0.6–0.75: good, and 40.75: excellent agreement. The mean and the standard error of the mean (SEM) were also used to provide an absolute index of the reliability within individual subjects (Weir 2005). The design of the experiment also corresponded to a repeated measurements framework. Four-way analysis of variance (ANOVA) with repeated measures was performed to assess the effects of the within-subject factors of trial, session, day, and site and between-subject factor of gender. Two-tailed tests with a significance level of 5% were used throughout. All statistical calculations were performed by using the Statistical Package for Social Sciences version 16 (SPSS, IBM, Armonk, NY, USA).
Results All subjects completed the study. The absolute values of all variables CDT, WDT, CPT, and HPT for the two genders at
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Somatosens Mot Res, 2014; 31(4): 198–203
Table I. The absolute means and SDs for all thermal threshold variables by different days, sessions, and trials in different gender at two test sites. Site (left hand) Gender Men
Session
Trial
CDT ( C)
WDT ( C)
CPT ( C)
HPT ( C)
CDT ( C)
WDT ( C)
CPT ( C)
HPT ( C)
1
1
1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3
29.7 ± 2.0 30.1 ± 1.7 30.6 ± 1.2 30.3 ± 1.5 30.5 ± 1.1 30.7 ± 1.1 30.3 ± 1.3 30.6 ± 1.7 30.4 ± 1.5 29.3 ± 2.2 30.1 ± 1.8 30.4 ± 1.9 30.6 ± 1.1 30.6 ± 1.5 30.6 ± 1.7 30.0 ± 1.1 30.3 ± 1.0 30.2 ± 1.2
34.0 ± 0.8 34.1 ± 1.0 33.8 ± 1.2 34.1 ± 0.7 33.5 ± 0.9 34.1 ± 0.9 33.9 ± 0.9 33.7 ± 1.1 34.0 ± 1.0 34.0 ± 1.3 33.9 ± 0.9 34.2 ± 1.3 34.1 ± 1.6 34.1 ± 1.9 34.1 ± 2 34.1 ± 1.1 34.2 ± 1.5 34.0 ± 1.5
11.0 ± 10.1 10.3 ± 9.3 10.6 ± 9.3 11.8 ± 9.9 10.6 ± 8.5 10.2 ± 9.0 13.0 ± 9.6 11.6 ± 8.9 11.0 ± 8.5 12.7 ± 8.1 12.5 ± 7.3 11.8 ± 7.2 13.2 ± 8.8 12.6 ± 7.7 10.7 ± 7.5 12.6 ± 9.1 11.6 ± 8.3 10.7 ± 7.9
42.7 ± 3.0 43.5 ± 3.1 44.1 ± 3.7 43.3 ± 3.1 45.0 ± 2.5 45.4 ± 3.3 43.5 ± 3.3 44.8 ± 3.7 45.6 ± 3.5 42.5 ± 1.6 43.5 ± 1.5 44.1 ± 2.5 43.6 ± 2.6 44.7 ± 3.0 44.9 ± 3.1 44.5 ± 2.2 45.2 ± 2.0 45.7 ± 2.3
30.4 ± 1.4 30.7 ± 0.9 30.9 ± 0.9 30.7 ± 1.0 30.7 ± 1.4 30.9 ± 1.0 30.5 ± 1.1 30.7 ± 1.1 30.7 ± 1.1 30.6 ± 0.5 30.8 ± 0.4 30.9 ± 0.6 30.7 ± 0.9 31.0 ± 1.0 30.9 ± 1.3 30.6 ± 0.8 30.7 ± 0.8 30.9 ± 0.8
34.3 ± 1.3 34.3 ± 1.0 34.2 ± 0.8 33.9 ± 1.1 34.0 ± 0.7 33.8 ± 0.6 34.0 ± 0.9 34.1 ± 0.9 33.9 ± 0.8 34.1 ± 1.0 33.8 ± 1.0 34.1 ± 1.0 34.0 ± 1.1 34.0 ± 1.2 34.0 ± 1.0 34.2 ± 0.9 34.2 ± 1.3 34.2 ± 1.2
6.9 ± 10.0 7.9 ± 9.8 10.0 ± 11.7 9.2 ± 11.0 8.1 ± 11.0 7.6 ± 10.0 7.5 ± 9.7 6.4 ± 9.2 6.6 ± 8.9 10.7 ± 10.4 9.6 ± 9.6 9.0 ± 9.5 10.1 ± 10.6 9.4 ± 9.9 8.9 ± 9.7 8.7 ± 8.8 7.7 ± 9.0 7.8 ± 7.9
42.4 ± 2.7 42.5 ± 3.0 43.5 ± 3.4 42.3 ± 3.9 43.8 ± 4.0 44.3 ± 4.2 44.0 ± 3.2 44.7 ± 3.1 44.9 ± 3.5 42.3 ± 2.4 43.4 ± 2.9 43.8 ± 3.1 42.9 ± 2.9 43.6 ± 2.9 44.2 ± 3.0 44.2 ± 2.2 44.5 ± 2.3 45.2 ± 2.7
1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3
30.1 ± 2.0 30.1 ± 1.5 30.6 ± 0.8 30.7 ± 0.7 30.8 ± 0.7 31.0 ± 0.6 30.5 ± 1.2 30.7 ± 1.4 30.6 ± 1.1 29 ± 2.3 29.4 ± 2.2 29.9 ± 1.7 30.0 ± 2.0 30.0 ± 1.8 30.3 ± 1.5 29.9 ± 1.9 30.4 ± 1.1 30.5 ± 1.2
33.6 ± 0.6 33.6 ± 0.7 33.8 ± 0.8 33.2 ± 0.6 33.6 ± 0.7 33.7 ± 0.8 33.9 ± 1.0 33.9 ± 1.2 34.1 ± 1.3 34.3 ± 1.2 34.0 ± 1.3 34.0 ± 1.3 33.6 ± 1.0 33.8 ± 0.9 33.9 ± 0.8 33.7 ± 1.1 34.2 ± 1.5 34.3 ± 1.8
20.4 ± 8.6 19.9 ± 7.8 19.8 ± 7.7 22.5 ± 4.3 19.4 ± 5.7 18.7 ± 6.1 21.0 ± 6.3 18.9 ± 6.3 17.4 ± 7.3 24.0 ± 6.1 22.6 ± 5.7 21.3 ± 5.6 23.7 ± 3.8 21.9 ± 4.8 20.9 ± 6.1 22.1 ± 8.1 20.8 ± 7.4 20.5 ± 7.7
38.3 ± 2.7 38.5 ± 2.6 40.3 ± 2.8 41.1 ± 1.7 43.3 ± 2.2 44.3 ± 1.9 41.7 ± 2.8 43.8 ± 2.2 45.0 ± 2.3 40.0 ± 3.0 41.3 ± 3.5 41.8 ± 6.6 40.4 ± 3.1 42.1 ± 3.5 42.4 ± 3.5 41.6 ± 3.5 42.8 ± 3.7 43.5 ± 3.1
30.8 ± 1.1 30.7 ± 1.0 31.2 ± 0.4 30.9 ± 0.7 30.8 ± 1.0 31.1 ± 0.5 30.9 ± 0.7 30.9 ± 0.6 31 ± 1.0 30.4 ± 1.0 31.0 ± 0.5 31.0 ± 0.6 30.8 ± 0.6 31.1 ± 0.4 31.2 ± 0.3 30.6 ± 1.1 31.1 ± 0.5 31.1 ± 0.6
34.0 ± 0.7 33.9 ± 0.9 33.9 ± 0.9 33.7 ± 0.5 33.6 ± 0.7 33.6 ± 0.6 33.7 ± 0.8 33.7 ± 1.1 33.7 ± 1.0 33.9 ± 1.0 33.9 ± 0.9 33.8 ± 0.7 33.8 ± 1.1 33.6 ± 0.8 33.7 ± 0.7 33.7 ± 0.7 33.7 ± 0.8 33.9 ± 1.0
24.8 ± 5.9 23.5 ± 6.2 23.1 ± 5.7 24.1 ± 6.5 22.4 ± 7 21.8 ± 5.9 23.3 ± 8.1 21.1 ± 8.5 19.6 ± 8.3 26.6 ± 5.4 25.8 ± 5.0 24.9 ± 5.8 26.9 ± 4.1 25.6 ± 4.9 24.1 ± 5.2 25.6 ± 6.0 24.1 ± 6.3 23.4 ± 5.5
37.9 ± 2.6 38.8 ± 2.7 39.4 ± 2.9 39.6 ± 3.7 40.6 ± 3.3 41.6 ± 3.8 40.1 ± 3.7 41.4 ± 3.7 42.6 ± 3.8 38.8 ± 3.0 39.3 ± 3.2 40.1 ± 3.5 39.0 ± 2.7 40.2 ± 3.5 41.0 ± 3.7 40.0 ± 3.4 41.0 ± 3.8 42.1 ± 4.2
3 2
1 2 3
Women
1
1 2 3
2
1 2 3
Site (left masseter)
Day
2
the two test sites over three trials, three sessions, and two days (one week apart) are presented as means and SDs in Table I. Most of the thermal thresholds were stable over the three sessions and two days while some variables, for example, CDT, CPT, and HPT, showed some difference between sites or gender.
test–retest reliabilities in the fair range. Table III lists the mean and SEM of all thermal thresholds for the two sites. In general, the SEMs indicated low variability. Moreover, the test–retest reliability data were supplemented by ANOVAs with repeated measurement to further characterize the time effects (trials, sessions, and days).
The intra-examiner test–retest reliability for all variables over different time intervals
Test of within-subject and between-subject effects for all variables in different gender at two sites over different time intervals
Table II lists the ICC values and 95% CI of all thermal thresholds over the three trials, three sessions, and two days for the two sites. The test–retest reliability of all thermal thresholds (CDT, WDT, CPT, and HPT) showed excellent agreement and the ICC values of all variables were 1 between different trials (Table II). The ICC values of all thermal thresholds at two test sites also showed excellent agreement (ranged from 0.791 to 0.977) over the different sessions. However, over different days, some variables of thermal pain threshold, including CPT and HPT, were associated with test–retest reliabilities that ranged from good to excellent (ranged from 0.611 to 0.837). Other variables of thermal detection threshold including CDT (ICChand ¼ 0.589, ICCmasseter ¼ 0.566) and WDT (ICChand ¼ 0.415, ICCmasseter ¼ 0.569) were associated with
The four-way ANOVA showed significant main effects of trials for CDT (p50.01), CPT (p ¼ 0.02), and HPT (p50.01) but not for WDT (p ¼ 0.503). Generally, the first trial for CDT, CPT, and HPT tended to reflect higher sensitivity (higher thresholds for CDT and CPT, lower thresholds for HPT) compared with the subsequent two trials (Table IV). There were no significant main effects of session for CDT (p ¼ 0.437), WDT (p ¼ 0.744), or CPT (p ¼ 0.318) whereas the HPT varied across sessions (p50.01; Table IV) with lower values in the first session compared to the last session. There were no significant main effects of days for CDT (p ¼ 0.398), WDT (p ¼ 0.223), CPT (p ¼ 0.264), or HPT (p ¼ 0.943) between the two weeks (Table IV).
Reliability study of thermal quantitative sensory testing in healthy Chinese
DOI: 10.3109/08990220.2014.914485
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Table II. Test–retest reliability measurements for all thermal threshold variables at two sites over three trials, three sessions, and two days.
Site
Variables
ICC (95% CI) across different trials
ICC (95% CI) across different sessions
ICC (95% CI) across different days
Left hand
CDT CPT HPT WDT
0.932 0.981 0.949 0.913
(0.907–0.950) (0.974–0.986) (0.931–0.963) (0.882–0.937)
0.848 (0.795–0.890) 0.964 (0.951–0.974) 0.791 (0.716–0.848) 0.8 (0.729–0.855)
0.589 0.752 0.611 0.415
(0.448–0.693) (0.667–0.815) (0.439–0.721) (0.214–0.564)
Left masseter
CDT CPT HPT WDT
0.912 0.989 0.976 0.919
(0.880–0.936) (0.985–0.992) (0.967–0.982) (0.890–0.941)
0.89 (0.851–0.920) 0.977 (0.968–0.983) 0.902 (0.867–0.929) 0.875 (0.830–0.909)
0.566 0.837 0.646 0.569
(0.418–0.677) (0.781–0.879) (0.526–0.737) (0.421–0.678)
The values were reported as intraclass correlation coefficient (ICC) and 95% confidence interval (95% CI) for all variables over three different sessions at the different day and over two different days. ICC50.4 is considered poor, 0.4–0.59: fair, 0.6–0.75: good, and 40.75: excellent agreement. Table III. The mean and SEM of all thermal thresholds across different trials, sessions, and days for the two sites.
Site Left hand
CDT WDT CPT HPT Time interval Mean SEM Mean SEM Mean SEM Mean SEM Trial 1 2 3 Session 1 2 3 Day 1 2 Total
Left Trial masseter 1 2 3 Session 1 2 3 Day 1 2 Total
30.02 0.15 33.87 0.09 17.33 0.83 41.93 0.29 30.30 0.14 33.89 0.10 16.05 0.77 43.19 0.30 30.48 0.12 33.99 0.11 15.28 0.78 43.91 0.33 29.95 0.16 33.92 0.09 16.40 0.83 41.70 0.34 30.48 0.12 33.82 0.10 16.34 0.77 43.36 0.28 30.37 0.12 34.00 0.11 15.93 0.80 43.96 0.28
Table IV. Test of within-subject and between-subject effects for CDT, WDT, CPT, and HPT in different gender at two sites over three trials, three sessions, and two days (one week apart) by four-way ANOVAs with repeated measures. CDT F
CPT p
F
Site 11.936 0.003* 2.12 Day 1.711 0.398 1.327 Session 0.641 0.437 1.167 Trial 9.14 0.005* 6.26 Gender 0.021 0.887 16.296
HPT p
F
WDT p
F
0.163 4.654 0.045 0 0.264 0.005 0.943 1.592 0.318 15.953 0.001* 0.168 0.02* 94.086 0.000* 0.619 0.001* 16.962 0.001* 0.663
p 0.994 0.223 0.744 0.503 0.426
*Indicates significant difference (p50.05). 30.45 0.10 33.80 0.07 15.44 0.66 42.99 0.26 30.07 0.12 34.03 0.10 17.00 0.63 43.02 0.26 30.26 0.08 33.92 0.06 16.22 0.46 43.01 0.18
Discussion 30.66 0.08 33.94 0.09 17.03 1.05 41.11 0.33 30.85 0.08 33.89 0.09 15.96 1.02 41.95 0.33 30.98 0.07 33.90 0.08 15.56 0.98 42.73 0.35 30.77 0.08 34.01 0.08 16.89 1.02 41.01 0.32 30.91 0.08 33.81 0.08 16.50 1.01 41.90 0.35 30.81 0.08 33.91 0.09 15.16 1.01 42.89 0.33 30.81 0.07 33.89 0.06 15.21 0.83 41.90 0.29 30.85 0.06 33.93 0.07 17.16 0.82 41.97 0.27 30.83 0.04 33.91 0.05 16.18 0.59 41.93 0.20
Site effects There were significant site differences for CDT as shown in Table II. The multiple comparison test (Bonferroni) revealed the CDT at the left hand was lower (lower sensitivity) than at the left masseter (p ¼ 0.003). Furthermore, a significant site effect was observed for HPT, with higher (lower sensitivity) values at the left hand than at the left masseter (p ¼ 0.045) (Table II). Subject and gender effects There was no significant age difference between men and women (p ¼ 0.191). There were significant gender differences with lower thresholds in men (lower sensitivity) than in women for CPT (p ¼ 0.001) and higher thresholds in men (lower sensitivity) than in women for HPT (p ¼ 0.001) (Table II).
The present study provided new aspects of the test–retest reliability of thermal QST in the trigeminal and spinal system in healthy Chinese. CDT, WDT, CPT, and HPT were measured at two sites: the surface of the left hand and left masseter for 20 healthy volunteers (10 women and 10 men). The testing was performed over three consecutive stimuli trials, three sessions conducted on one day and repeated one week later. The results show that the test–retest reliability of most thermal threshold measures was acceptable to excellent for assessing somatosensory function, however, test site and gender affect thermal thresholds substantially. To our knowledge the present study, for the first time, investigated these important aspects of the test–retest reliability of thermal QST in the trigeminal and spinal system in a non-Caucasian population. Absolute data of thermal QST Thermal QST are recognized to be potentially valuable to assess small-fiber function, but their widespread use has been discouraged because reference values from different studies are inhomogeneous (Magerl et al. 2010). The mean values of our absolute thermal QST data in a Chinese population compare well with prior studies for thermal detection and pain thresholds (Lang et al. 2006; Wasner and Brock 2008). Yang et al. (2013) observed significant differences in thermal sensitivity in the trigeminal region between a Caucasian and Chinese population.
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Wide ranges for thermal QST data in individual cases were seen, as also occurred in the study by Rolke et al. (2006a) on 180 healthy volunteers as well as former studies (Yarnitsky et al. 1995; Klauenberg et al. 2008). The relatively large variability indicates that the references of these QST measures are wide, affecting clinical utilization. This calls for adequate reference groups, standardization of QST methodologies and test protocols, and also the need to establish appropriate measures of test–retest reliability. There are several possible explanations for the variability of QST measures. One obvious explanation in addition to methodological differences may be that QST is a psychophysical method which is strongly influenced by the interaction and communication between the test subject and the examiner, and furthermore, that the QST outcome depends on the motor abilities and attention of the patient (Hansson et al. 2007). Mental factors may also influence individual thermal detection and pain thresholds in orofacial pain patients, for example, anxiety, former pain experiences, and coping strategies. All these factors need to be considered in order to interpret the QST outcome correctly. The present study provides a basis to implement thermal QST in a Chinese population. Gender and site differences in somatosensory function The reported results are similar to several other studies that found women more sensitive than men for many thermal QST parameters (Riley et al. 1998). However, the present findings indicate that gender differences were present only for pain thresholds including CPT and HPT. Since thermal detection thresholds were independent of gender, the differences in pain thresholds are unlikely to be due to peripheral factors such as innervation density, and may be attributed to different central processing (Rollman and Lautenbacher 2001; Sarlani et al. 2003). As it has been reported that women are more sensitive to thermal stimuli (Hansson et al. 2007; Blankenburg et al. 2011), a thorough understanding of developmental and sexrelated differences in pain perception is important. LeResche et al. used epidemiological studies for pain detection in children and adolescents and found that marked sex differences arising around puberty, with girls reporting greater and more frequent pain than boys (LeResche et al. 2005; KronerHerwig et al. 2007). At the same time Riley et al. found marked sex differences are present in adults with females more sensitive to thermal stimuli than males (Riley et al. 1998; Rolke et al. 2006a; Blankenburg et al. 2010). The results of our study are in accordance with the former studies. The present study also demonstrated that absolute threshold values varied between two anatomical sites and our results are in accordance with former studies (Rolke et al. 2006a). Sensitivity was higher on the face than on the hand for CDT and HPT. We suspect that it may be due to the decreased distance to the central nervous system (CNS) when comparing the face with the hand. Our results suggest that to determine whether somatosensory changes have occurred, it is important to consider the site being tested.
Somatosens Mot Res, 2014; 31(4): 198–203
Time effect on the reliability of thermal QST parameters We have analyzed both the trial, session, and week effects on the reliability of thermal QST. A one-week interval between assessments was used as it might be a reasonable time interval relevant for clinical studies or patient follow-up. While test– retest reliability of repeated assessments over consecutive days has been established in former studies, few studies have assessed repeated within-session and trial-to-trial assessment (Cathcart and Pritchard 2006; Pigg et al. 2010; Moloney et al. 2011). Interestingly and importantly, we found that the first trial for CDT, CPT, and HPT tended to reflect higher sensitivity compared with the subsequent two trials. This result may be explained as habituation which is described as a behavioral response decrement that results from repeated stimulation (Thompson and Spencer 1966). In thermal QST, the application of repetitive thermal stimuli on a fixed location could lead to increased thresholds and less sensitivity. The habituation may be due to the increasing fatigue of A- and C-fiber nociceptors (Greffrath et al. 2007). The reliability of all thermal thresholds at the two test sites showed excellent agreement (ranged from 0.791 to 0.977) over different sessions and trials. However, over different days, some variables of thermal pain threshold, including CPT and HPT, showed good to excellent reliabilities; while CDT and WDT were only fair. Moreover, we used the SEM to provide an absolute index of reliability which is not affected by the between-subject variability as is the ICC. The result showed the SEM values were relatively small for all thermal thresholds. In our study, there were no significant main effects of session for CDT, WDT, or CPT whereas HPT varied across sessions with lower values in the first session compared to the last session. The poorer reproducibility between sessions for HPT implies that HPT assessment is associated with greater uncertainty and therefore that clinical differences may be more difficult to detect. In contrast, others have reported better HPT reliability on the facial skin (Geber et al. 2011; Wylde et al. 2011) although considerable within-subject variability in HPT has also been found in previous studies (Geber et al. 2011; Moloney et al. 2011, 2012). In our study, HPT reliability varied greatly between different sessions. The reasons for this variability are unknown but could reflect variations in heat pain sensitive afferent fiber density or biophysical properties. In conclusion, this study’s main findings are that the test– retest reliability of thermal QST parameters is acceptable to excellent and that the DFNS protocol can be applied in a healthy Chinese population. This shows that thermal QST is feasible and repeatable for use in future applications such as the establishment of normative values and possibly for mechanism-based profiling of orofacial pain. However, the limitation of this study may be that, due to the relatively small sample size, inclusion of healthy controls and the applied fixed time intervals, the power could have been insufficient to allow detection of more subtle differences. Future studies will be needed to record from larger groups of matched subjects and orofacial pain patients to highlight possible variation over different time intervals.
DOI: 10.3109/08990220.2014.914485
Reliability study of thermal quantitative sensory testing in healthy Chinese
Declaration of interest The authors report no conflicts of interest. This work was supported by National Natural Science Foundation of China (Grant Nos. 30973361 and 81170981); Jiangsu Government scholarship for overseas study (Grant No. JS-2009-083); PhD Programs Foundation of Ministry of Education of China (Grant No. 20113234110003); and the Priority Academic Program Development of Jiangsu Higher Education Institutions. A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institute (Grant No. 2014-37).
References Aggarwal VR, Macfarlane TV, Macfarlane GJ. 2003. Why is pain more common amongst people living in areas of low socio-economic status? A population-based cross-sectional study. Br Dent J 194: 383–387; discussion 380. Aggarwal VR, McBeth J, Zakrzewska JM, Lunt M, Macfarlane GJ. 2006. The epidemiology of chronic syndromes that are frequently unexplained: Do they have common associated factors? Int J Epidemiol 35: 468–476. Blankenburg M, Boekens H, Hechler T, Maier C, Krumova E, Scherens A, Magerl W, Aksu F, Zernikow B. 2010. Reference values for quantitative sensory testing in children and adolescents: Developmental and gender differences of somatosensory perception. Pain 149:76–88. Blankenburg M, Meyer D, Hirschfeld G, Kraemer N, Hechler T, Aksu F, Krumova EK, Magerl W, Maier C, Zernikow B. 2011. Developmental and sex differences in somatosensory perception—A systematic comparison of 7- versus 14-year-olds using quantitative sensory testing. Pain 152:2625–2631. Cathcart S, Pritchard D. 2006. Reliability of pain threshold measurement in young adults. J Headache Pain 7:21–26. Geber C, Klein T, Azad S, Birklein F, Gierthmuhlen J, Huge V, Lauchart M, Nitzsche D, Stengel M, Valet M, et al. 2011. Test–retest and interobserver reliability of quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain (DFNS): A multi-centre study. Pain 152:548–556. Greffrath W, Baumgartner U, Treede RD. 2007. Peripheral and central components of habituation of heat pain perception and evoked potentials in humans. Pain 132:301–311. Hansson P. 2002. Neuropathic pain: Clinical characteristics and diagnostic workup. Eur J Pain 6(Suppl. A):47–50. Hansson P, Backonja M, Bouhassira D. 2007. Usefulness and limitations of quantitative sensory testing: Clinical and research application in neuropathic pain states. Pain 129:256–259. Jamal GA, Hansen S, Weir AI, Ballantyne JP. 1987. The neurophysiologic investigation of small fiber neuropathies. Muscle Nerve 10: 537–545. Klauenberg S, Maier C, Assion HJ, Hoffmann A, Krumova EK, Magerl W, Scherens A, Treede RD, Juckel G. 2008. Depression and changed pain perception: Hints for a central disinhibition mechanism. Pain 140:332–343. Kroner-Herwig B, Heinrich M, Morris L. 2007. Headache in German children and adolescents: A population-based epidemiological study. Cephalalgia 27:519–527. Krumova EK, Zeller M, Westermann A, Maier C. 2012. Lidocaine patch (5%) produces a selective, but incomplete block of Adelta and C fibers. Pain 153:273–280. Lam VY, Wallace M, Schulteis G. 2011. Effects of lidocaine patch on intradermal capsaicin-induced pain: A double-blind, controlled trial. J Pain 12:323–330.
203
Lang PM, Schober GM, Rolke R, Wagner S, Hilge R, Offenbacher M, Treede RD, Hoffmann U, Irnich D. 2006. Sensory neuropathy and signs of central sensitization in patients with peripheral arterial disease. Pain 124:190–200. LeResche L, Mancl LA, Drangsholt MT, Saunders K, Korff MV. 2005. Relationship of pain and symptoms to pubertal development in adolescents. Pain 118:201–209. List T, Helkimo M, Falk G. 1989. Reliability and validity of a pressure threshold meter in recording tenderness in the masseter muscle and the anterior temporalis muscle. Cranio 7:223–229. Magerl W, Krumova EK, Baron R, Tolle T, Treede RD, Maier C. 2010. Reference data for quantitative sensory testing (QST): Refined stratification for age and a novel method for statistical comparison of group data. Pain 151:598–605. Moloney NA, Hall TM, O’Sullivan TC, Doody CM. 2011. Reliability of thermal quantitative sensory testing of the hand in a cohort of young, healthy adults. Muscle Nerve 44:547–552. Moloney NA, Hall TM, Doody CM. 2012. Reliability of thermal quantitative sensory testing: A systematic review. J Rehabil Res Dev 49:191–207. Pigg M, Baad-Hansen L, Svensson P, Drangsholt M, List T. 2010. Reliability of intraoral quantitative sensory testing (QST). Pain 148: 220–226. Riley 3rd JL, Robinson ME, Wise EA, Myers CD, Fillingim RB. 1998. Sex differences in the perception of noxious experimental stimuli: A meta-analysis. Pain 74:181–187. Rolke R, Baron R, Maier C, Tolle TR, Treede RD, Beyer A, Binder A, Birbaumer N, Birklein F, Botefur IC, et al. 2006a. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values. Pain 123: 231–243. Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein F, Treede RD. 2006b. Quantitative sensory testing: A comprehensive protocol for clinical trials. Eur J Pain 10:77–88. Rollman GB, Lautenbacher S. 2001. Sex differences in musculoskeletal pain. Clin J Pain 17:20–24. Sarlani E, Farooq N, Greenspan JD. 2003. Gender and laterality differences in thermosensation throughout the perceptible range. Pain 106:9–18. Thompson RF, Spencer WA. 1966. Habituation: A model phenomenon for the study of neuronal substrates of behavior. Psychol Rev 73: 16–43. Tobin K, Giuliani MJ, Lacomis D. 1999. Comparison of different modalities for detection of small fiber neuropathy. Clin Neurophysiol 110:1909–1912. Wasner G, Naleschinski D, Baron R. 2007. A role for peripheral afferents in the pathophysiology and treatment of at-level neuropathic pain in spinal cord injury? A case report. Pain 131:219–225. Wasner GL, Brock JA. 2008. Determinants of thermal pain thresholds in normal subjects. Clin Neurophysiol 119:2389–2395. Weir JP. 2005. Quantifying test–retest reliability using the intraclass correlation coefficient and the SEM. J Strength Cond Res 19:231–240. Wylde V, Palmer S, Learmonth ID, Dieppe P. 2011. Test–retest reliability of Quantitative Sensory Testing in knee osteoarthritis and healthy participants. Osteoarthritis Cartilage 19:655–658. Yang G, Luo Y, Baad-Hansen L, Wang K, Arendt-Nielsen L, Xie QF, Svensson P. 2013. Ethnic differences in oro-facial somatosensory profiles—Quantitative sensory testing in Chinese and Danes. J Oral Rehabil 40:844–853. Yarnitsky D, Ochoa JL. 1991. Differential effect of compressionischaemia block on warm sensation and heat-induced pain. Brain 114(Pt 2):907–913. Yarnitsky D, Sprecher E, Zaslansky R, Hemli JA. 1995. Heat pain thresholds: Normative data and repeatability. Pain 60:329–332. Ziegler EA, Magerl W, Meyer RA, Treede RD. 1999. Secondary hyperalgesia to punctate mechanical stimuli. Central sensitization to A-fibre nociceptor input. Brain 122(Pt 12):2245–2257.
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