1. Introduction

Patients with chronic neuropathic pain experience a wide range of symptoms including positive (spontaneous/evoked pain, hyperalgesia, and allodynia) and negative sensory symptoms (hypoesthesia, hypoalgesia). These symptoms are often accompanied by comorbidities such as depression and impaired physical functioning, resulting in an overall reduced quality of life and significant burden for patients. Even first-line drugs often do not provide sufficient pain relief.8 Moreover, several encouraging new drugs have failed recently in clinical trials. One reason for this dilemma might be that chronic neuropathic pain syndromes are multifaceted disorders with different pathophysiological mechanisms, variably expressed in each individual independent of the underlying disease. Consequently, neuropathic pain syndromes should be grouped based on the underlying pathophysiological mechanisms of pain generation rather than on the disease etiology to establish a so-called mechanism-based treatment.19,28 Because no biomarkers of pain mechanisms have been discovered so far, one has to rely on surrogate markers that are believed to be closely linked to mechanisms of pain generation.1,25

One promising surrogate marker for dysfunction in pain pathways is the pattern of sensory symptoms and signs (sensory profile), as stratification approach2,26 and potential predictive biomarker for treatment response.5,11,23 The quantitative sensory testing (QST) protocol by the German Research Network on Neuropathic Pain (DFNS) is a standardized and valid method for neuropathic pain characterization through detection of sensory abnormalities of small and large nerve fibers or their corresponding pathways.22 This protocol allows subgrouping of patients into 3 clusters based on their somatosensory profiles, which are assumed to respond differentially to specific therapeutics.2 Consequently, the European Medicines Agency (EMA) has acknowledged in a Committee for Medicinal Products for Human Use qualification advice that sensory profiling and subgrouping of patients is an adequate stratification tool for determining specific sensory phenotypes of patients in exploratory trials on neuropathic pain.6

However, the use of the laboratory DFNS QST protocol (lab-QST) is limited to specialized centers due to high expenditures of time and costs and the need for training. To overcome these limitations and implement this profiling approach in clinical phase III trials and clinical practice, it is of utmost importance to develop an easy-to-use bedside assessment protocol. Recently, we presented a simple bedside-QST with good concurrent criterion validity, ie, correlation with lab-QST, which allows assignment to the 3 lab-QST clusters.21 To establish this bedside-QST battery for its use in clinical practice and large trials, this study aimed at assessing its test–retest reliability and convergent/divergent validity.

2. Methods 2.1. Study cohort

A total of 60 patients (34 men and 26 women) experiencing chronic pain with neuropathic features for at least 3 months were included. Only adults (aged 18 years or older) with sufficient German knowledge were included. Exclusion criteria were as follows: severe depression, alcohol or drug abuse, fibromyalgia, and other pain disorders within the same testing areas that may interfere with the pain ratings. Patients were recruited from the study centre's internal patient pool and through flyers placed in pharmacies and neurological medical practices. An expense allowance of 50€ was paid out, as well as parking fees and/or travel costs.

2.2. Study design

Patients attended the study site for 3 visits over 2 days, twice at the first day and again after approximately 3 weeks (Fig. 1). During the first visit (t1), demographic and clinical data, including pre-existing diseases, operations, (pain) medication, and pain duration, were collected. The exact pattern of symptoms, as well as pain-influencing factors, were elaborated. Pain intensity was rated on an 11-point numerical rating scale (NRS), recording the average, minimum, and maximum pain intensity during the past 24 hours before the study visit (0 = no pain; 10 = the worst pain imaginable).

Figure 1.:

Study protocol. HADS, Hospital Anxiety and Depression Scale; NRS, numerical rating scale; PGIC, Patient's Global Impression of Change.

Patients underwent a clinical neurological examination to define the most affected area and to map changes over the course of the 3 weeks. Afterwards, both the lab-QST and then the bedside-QST were performed. After 3 hours, the bedside-QST was repeated (t2, short-term reliability). Approximately 3 weeks later (3 ± 1 week), patients attended the study site for a third visit (t3). After a short interview regarding changes in pain, overall health state and medication, and a clinical neurological examination, patients underwent again both the lab-QST and the bedside-QST (long-term reliability).

Bedside-QST and lab-QST were performed first in a nonaffected, contralateral control area and afterwards in the most affected area (area of maximum pain). In case of a symmetric disease, the control examination was performed in a contralateral proximal area, eg, patients with a distal symmetric painful polyneuropathy were tested at the dorsum of the feet (test area) and the contralateral thigh (control area).

After both study days, patients filled out questionnaires regarding their pain intensity and quality, health, depression/anxiety, and quality of life. At t3, patients were asked about their pain course compared with that at t1 using the Patient's Global Impression of Change (PGIC; 1 = very much improved, 2 = moderately improved, 3 = minimally improved, 4 = unchanged, 5 = minimally worse, 6 = moderately worse, and 7 = very much worse).10 The whole examination including clinical examination, and sensory testing was performed by the same examiner, who received adequate training in both testing procedures by a QST-experienced neurologist-in-training before the participants' enrollment. The same neurologist also provided supervision during the study to ensure standardized performance of testing.

The study was conducted in accordance with the Declaration of Helsinki and approved by the local ethical committee of the University Hospital of Kiel (AZ: D454/15). Before study entry, all participants gave their written informed consent.

2.3. Questionnaires

The painPREDICT questionnaire is a self-administered questionnaire that consists of 20 items covering different nociceptive and neuropathic aspects of pain, ie, pain intensity, location of pain, course of pain, and sensory symptoms rated on a 10-point NRS.24

The EQ-5D-5L questionnaire is a generic measurement of health-related quality of life.7 It consists of 2 parts. The descriptive system includes 5 dimensions that are rated on a 5-point Likert scale (1 = no problem to 5 = unable/extreme problems). Based on the ratings, a 5-digit code can be calculated that reflects the patient's health state. This 5-digit code can be used to generate a country-based index value ranging from −0.661 = worst possible score to 1 = best possible score.17 In addition, patients rate their current health state on a visual analogue scale (EQ VAS) ranging from 100 = the best health you can imagine to 0 = the worst health you can imagine.

The Hospital Anxiety and Depression Scale (HADS) is used to screen for the presence of anxiety and depression in patients with chronic diseases.30 It consists of 14 items that are used to build 2 subscores, one for depression (HADS-D) and the other for anxiety (HADS-A). Optimal cutoff levels for possible anxiety and depressive disorders are scores ≥ 8.3

2.4. Laboratory quantitative sensory testing

Lab-QST was performed according to the standardized protocol of the DFNS.22 Different thermal and mechanical sensory stimuli were applied to skin or deep somatic structures to elicit a sensory sensation (painful or nonpainful), which was evaluated by the patients according to distinct criteria (intensity, painfulness). The DFNS protocol consists of 13 parameters, assessed by 7 different test devices (Supplement Table 1, available at https://links.lww.com/PR9/A179):

cold detection threshold and warm detection threshold (CDT, WDT), cold pain threshold and heat pain threshold (CPT, HPT), thermal sensory limen (TSL), presence of paradoxical heat sensations (PHS), mechanical pain threshold (MPT) and mechanical pain sensitivity (MPS), dynamic mechanical allodynia (DMA), pressure pain threshold (PPT), wind-up ratio (WUR), tactile (mechanical) detection threshold (MDT), and vibration detection threshold (VDT).

For statistical analysis, lab-QST z values were calculated that allow direct comparison with sex-matched, age-matched, and body-matched reference values of healthy controls.14Z scores of zero represent the mean value of healthy controls, z scores above “0” indicate a gain of function (hyperalgesia), and z scores below “0” indicate a loss of function (hypoesthesia, hypoalgesia). Z values exceeding the 95% confidence interval of reference data were defined as abnormal loss (<−1.96) or gain (>+1.96). Because DMA and PHS are absent under physiological conditions, calculation of z values is not possible. Instead, original (DMA = 0–100 numeric rating scale; PHS = numbers of PHS from 0 to 3) and dichotomous values (absent = normal; present = abnormal) were used.

2.5. Bedside-quantitative sensory testing

Bedside-QST follows a simple protocol using 11 cheap and easy-to-use devices (Supplement Table 1, available at https://links.lww.com/PR9/A179). Parameters that had achieved poor results in the previous study were excluded (brush, cotton-wool ball, 0.4-mm CMS hair). Thus, a simplification of the protocol was achieved. Because results of the 0.7-mm CMS hair were shown to be training dependent,21 the original protocol was complemented by the inclusion of a more standardized device, ie, the Neuropen, to test for pinprick hyperalgesia and temporal pain summation. A filament of the same device was also used for statical mechanical detection in addition to the 64-mN von Frey hair. Overall, patients had to rate (1) whether the stimulus was perceived/not perceived or painful/not painful (yes/no) and (2) the perception or pain intensity of each stimuli using an 11-point NRS (0 = no perception/no pain, 10 = strongest imaginable perception/strongest imaginable pain). A painful stimulus was defined as any burning, stinging, aching, or drilling sensation. For application details of the single stimuli, see Supplement material (available at https://links.lww.com/PR9/A179).

2.6. Statistical analysis

Statistical analysis was performed using IBM SPSS statistics for Windows (Version 25.0, NY).

Descriptive analysis of bedside-QST parameters was performed by calculating minimum, maximum, and average values, standard deviations for interval-scaled parameters (NRS-11), and frequencies/detection rates for dichotomized parameters (painful/perception, yes/no).

To confirm results of our first study and to investigate properties of the newly included bedside-QST tools, comparison of lab-QST and bedside-QST parameters was repeated as previously described.21 In brief, sensitivity/specificity, Spearman correlation coefficients, and receiver-operating characteristics (ROCs) were calculated.

Test–retest reliability of bedside-QST parameters was examined for short-term (t1–t2) and long-term (t1–t3) periods. Long-term test–retest reliability was calculated only for patients who indicated no change in their pain intensity between both study days (t1–t3) on the PGIC scale (PGIC = 4). Test–retest reliability of interval-scaled parameters (perception/pain intensity rating; NRS 0–10) was assessed using the intraclass correlation coefficient (ICC) under the random effect model according to Koo and Li: ICC of >0.9 = excellent, >0.75 = good, >0.5 = moderate, and <0.5 = poor correlation.14 The test–retest reliability of dichotomous parameters (painful or perception, yes/no) was performed using the Cohen Kappa coefficient according to Landis and Koch: Cohen Kappa of 0.81–1.0 = almost perfect, 0.61–0.8 = substantial, 0.41–0.6 = moderate, 0.21–0.4 = fair, 0 to 0.2 = light, and < 0 = poor correlation.16

Convergent/divergent validity was calculated by comparing the relationship of average pain intensity (NRS) and HADS scores with the bedside-QST items using the Spearman correlation coefficient. P values < 0.05 were considered statistically significant. Based on comparing 2 ratings each, an estimated average ICC between measurements of 0.5, a desired power of 80%, and an alpha level of 0.05, Bonferroni corrected for the number of reliability assessments, a sample size of n = 60 was determined to be sufficient and robust to up to 10% dropouts.

3. Results 3.1. Characteristics of the study cohort

All included patients (n = 60, 58.1 ± 15.4 years, 34 males, 26 females) completed all 3 study visits. Baseline demographic and clinical features are summarized in Table 1. Patients experienced different etiologies, most frequently painful polyneuropathy. Most of the patients (65.0%) reported no change in pain between t1 and t3, while the pain decreased in 8 (13.2%) and increased in 13 patients (21.7%).

Table 1 - Patient characteristics. Age [mean ± SD] (range) 58.0 ± 15.3 (21–82) Sex [n] (%)  Male 34 (56.7)  Female 26 (43.3) BMI [mean ± SD] (range) 27.9 ± 6.4 (18.3–56.9) Pain duration, y [mean ± SD] (range) 4.3 ± 4.4 (0.3–22) Diagnosis [n] (%)  Polyneuropathy 30 (50.0)  Postherpetic neuralgia 7 (11.7)  Central pain (ependymoma, syringomyelia, ganglioglioma surgery) 3 (5.0)  Complex regional pain syndrome (CRPS) 8 (13.3)  Peripheral nerve injury 3 (5.0)  Posttraumatic neuropathic pain 4 (6.7)  Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) 1 (1.7)  Trigeminal neuropathy 1 (1.7)  Carpal tunnel syndrome 1 (1.7)  Unspecified sensory deficitis 2 (3.3) Pain medication [n] (%)  Yes (at least 1) 44 (73.3)  No 16 (26.7)  NSAID 8 (13.3)  Metamizol 8 (13.3)  Opioids 10 (16.7)  Anticonvulsants 29 (48.3)  Antidepressants 14 (23.3)  Local anesthesia 11 (18.3)  Cannabinoids 2 (3.3)  Number of pain medications [mean ± SD] (range) 1.5 ± 1.4 (0–5) Test side [n] (%)  Foot 35 (58.3)  Hand 12 (20.0)  Trunk 5 (8.3)  Face 3 (5.0)  Forearm 2 (3.3)  Shoulder 1 (1.7)  Thigh 1 (1.7)  Lower leg 1 (1.7) Control side [n] (%)  Thigh 33 (55.0)  Hand 11 (18.3)  Trunk 5 (8.3)  Foot 3 (5.0)  Face 3 (5.0)  Forearm 2 (3.3)  Shoulder 1 (1.7)  Lower leg 1 (1.7)  Upper arm 1 (1.7) Relation between test and control side [n] (%)  Contralateral 27 (45)  Other 33 (55) Duration of bedside-QST, min [mean ± SD] (range)* 17.4 ± 2.4 (12–23)

*Data are only shown for the first visit (t1).

NSAID, Nonsteroidal anti-inflammatory drugs.

It took a maximum of 23 minutes to perform complete bedside-QST in 2 body areas (control and test area). Sensory testing was most frequently performed in the feet (test area) and the thigh (control area). Most of the reported symptoms assessed within the battery of questionnaires remained relatively stable between the 2 study days (t1 and t3) (Table 2). The average pain intensity during the past 24 hours before testing was scored on average with 4/10 on the NRS on both study days. The most frequently reported symptoms of the painPREDICT questionnaire were spontaneous numbness (71.4%, 75.0%) and spontaneous tingling sensations (70.0%, 67.9%). Rather uncommonly reported symptoms were spontaneous itching (25.0%, 19.6%) and pain evoked by something warm (26.8%, 23.2%). The general health state (EQ-5D-5L) revealed an average index value of 0.7, indicating a rather little impaired health-related quality of life, although with a wide range from 0.1 to 0.9. More than half of the patients did not show any evidence for anxiety or depression.

Table 2 - Questionnaire results comparing both study days. Questionnaire First study day (t1, t2) Second study day (t3) P 24 hours pain intensity NRS [mean ± SD] (range)  Average (n = 59) 4.2 ± 2.6 (0–10) 4.3 ± 2.5 (0–9) 0.729  Minimum (n = 58) 1.6 ± 1.7 (0–5) 1.7 ± 2.1 (0–7) 0.338  Maximum (n = 58) 6.7 ± 3.0 (0–10) 5.9 ± 3.0 (0–10) 0.001 PainPREDICT [mean ± SD] (yes, %)  Average pain in last 7 d 4.3 ± 2.2 4.3 ± 2.1 0.712  Worst pain in last 7 d 6.2 ± 2.7 6.1 ± 2.6 0.507  Spontaneous burning sensation 3.5 ± 3.5 (57.1) 3.6 ± 3.3 (62.5) 0.876  Spontaneous tingling sensation 3.9 ± 3.1 (70.0) 3.3 ± 3.2 (67.9) 0.016  Spontaneous itching 1.1 ± 2.4 (25.0) 0.8 ± 2.1 (19.6) 0.294  Spontaneous numbness 4.5 ± 3.7 (71.4) 4.6 ± 3.5 (75.0) 0.956  Spontaneous pain in numb areas (6 missing values) 3.1 ± 3.4 (53.6) 3.4 ± 3.4 (58.9) 0.315  Spontaneous cold sensation 2.7 ± 3.4 (46.4) 2.8 ± 3.2 (51.8) 0.983  Squeezing 2.8 ± 3.1 (57.1) 2.7 ± 3.0 (53.6) 0.686  Deep pressure sensation 3.2 ± 3.4 (55.4) 3.1 ± 3.3 (53.6) 0.950  Swelling feeling (5 missing values) 2.9 ± 3.4 (51.8) 2.8 ± 3.2 (55.4) 0.954  Tense muscles 3.0 ± 3.6 (48.2) 3.5 ± 3.8 (53.6) 0.131  Sudden pain that occurred for no particular reason 4.4 ± 3.7 (64.3) 3.5 ± 3.7 (51.8) 0.024  Sudden pain caused by moving, staying in the same position, or changing positions 4.2 ± 3.7 (62.5) 4.0 ± 3.7 (60.7) 0.431  Pain when brushed against lightly 2.2 ± 3.1 (44.6) 2.0 ± 3.1 (39.3) 0.307  Pain by slight pressure 2.8 ± 3.1 (53.6) 2.4 ± 2.9 (50.0) 0.343  Pain caused by a pointed object touching (nb = 5) 2.3 ± 3.2 (41.8) 2.3 ± 3.3 (44.6) 0.730  Pain by something cold 2.1 ± 3.0 (42.9) 2.1 ± 2.9 (42.9) 0.987  Pain by something warm 1.2 ± 2.2 (26.8) 1.3 ± 2.7 (23.2) 0.652 EQ-5D-5L 0.143  Index value (−0.661–1) [mean ± SD] (range) (n = 56) 0.7 ± 0.3 (−0.2–0.9) 0.7 ± 0.3 (−0.0–1.0)  VAS 57.9 ± 21.3 (15–95) 56.4 ± 20.7 (10–95) HADS-A score [mean ± SD] (range) 5.9 ± 4.4 (0–19) 5.5 ± 4.6 (0–19) 0.252  Conspicuous (≥8) [n] (%) 20 (33.3) 21 (35.0)  Inconspicuous (<8) [n] (%) 40 (66.7) 39 (65.0) HADS-D score [mean ± SD] (range) 5.6 ± 3.6 (0–15) 5.9 ± 4.2 (0–15) 0.186  Conspicuous (≥8) [n] (%) 15 (25.0) 22 (36.7)  Inconspicuous (<8) [n] (%) 45 (75.0) 38 (63.3) PGIC  Pain decreased (1–3) [n] (%) 8 (13.3)  No change (4) [n] (%) 39 (65.0)  Pain increased (5–7) [n] (%) 13 (21.7)

n = 4 missing values for t1 and/or t3 for all questionnaires except for the NRS and PGIC. Differences for mean values of questionnaires comparing t1 and t3 were calculated using the Wilcoxon test (P < 0.05 = significant). Significant correlations are marked in bold.

NRS, numerical rating scale; HADS, hospital anxiety and depression scale; PGIC, Patient's Global Impression of Change.

3.2. Laboratory quantitative sensory testing results

The patient cohort was dominated by profound negative sensory signs, ie, abnormal loss to nonpainful thermal (cold detection threshold and warm detection threshold, TSL) and mechanical parameters (mechanical detection threshold and vibration detection threshold) (Fig. 2). Positive sensory signs were less frequently observed (most often pressure pain hyperalgesia and paradoxical heat sensations). Other positive sensory signs such as thermal hyperalgesia or pinprick hyperalgesia were rare overall.

Figure 2.:

Lab-QST in patients (n = 60). (A) Somatosensory profile. (B) Frequencies of abnormal values. QST, quantitative sensory testing. CDT, cold detection threshold; CPT, cold pain threshold; DMA, dynamic mechanical allodynia; HPT, heat pain threshold; MDT, mechanical detection threshold; MPT, mechanical pain threshold; MPS, mechanical pain sensitivity; PHS, paradoxical heat sensation; PPT, pressure pain threshold; TSL, thermal sensory limen; VDT, vibration detection threshold; WDT, warm detection threshold; WUR, wind-up ratio.

3.3. Bedside-quantitative sensory testing results

Table 3 summarizes the results of the descriptive analysis of all bedside-QST parameters. Note that for some bedside-QST parameters, the detection rate was low, ie, PHS to 22 and 8°C metal, thermal hyperalgesia to 22 and 37°C. Comparison of lab-QST vs bedside-QST revealed similar results as previously described.21 All parameters with good discriminative values in the previous study, ie, “loss of cold perception to 22°C metal,” “hypersensitivity towards 45°C metal,” “loss of tactile perception to Q-tip,” “loss of pain perception to 0.7 mm CMS hair,” and “Q-tip allodynia” showed comparable sensitivity and specificity values (Supplement Table 2, available at https://links.lww.com/PR9/A179). The new tools (Neuropen/Neurotip) showed comparable results to their counterpart in the original bedside-QST (64 mN von Frey hair/CMS hair).

Table 3 - Descriptive analysis of bedside-quantitative sensory testing (QST) parameters (test side). Bedside-QST Visit n Min Max Mean (±SD) Detection rate (yes; n, %) Thermal parameters Metal 22°C
Perception intensity t1
t2
t3 60
60
60 0
0
0 8
6
8 2.3 (±2.4)
2.0 (±1.7)
2.2 (±2.3) 39 (65)
45 (75)
40 (66.7) Metal 22°C
Paradoxic heat sensation t1
t2
t3 60
60
60 — — — 3 (5)
1 (1.7)
2 (3.3) Metal 08°C
Perception intensity t1
t2
t3 60
60
60 0
0
0 10
10
10 3.3 (±2.5)
3.4 (±2.5)
3.3 (±2.6) 53 (88.3)
52 (86.7)
50 (83.3) Metal 08°C
Paradoxic heat sensation t1
t2
t3 60
60
60 — — — 4 (6.7)
3 (5.0)
3 (5.0) Metal 37°C
Perception intensity t1
t2
t3 60
60
60 0
0
0 8
8
8 2.3 (±2.3)
2.4 (±2.2)
2.1 (±2.3) 44 (73.3)
44 (73.3)
40 (66.7) Metal 45°C
Perception intensity t1
t2
t3 60
60
60 0
0
0 10
10
10 4.4 (±3.2)
4.5 (±3.2)
4.4 (±3.1) 48 (80)
50 (83.3)
52 (86.7) Metal 22°C
Pain intensity t1
t2
t3 59*
60
59* 0
0
0 8
6
6.5 0.8 (±1.9)
0.2 (±0.9)
0.6 (±1.5) 11 (18.3)
4 (6.7)
11 (18.3) Metal 08°C
Pain intensity t1
t2
t3 60
59*
60 0
0
0 9.5
7
9 0.9 (±2.2)
0.7 (±1.6)
0.8 (±1.9) 13 (21.7)
11 (18.3)
12 (20.0) Metal 37°C
Pain intensity t1
t2
t3 60
60
60 0
0
0 3
4
6 0.1 (±0.6)
0.4 (±1.0)
0.3 (±1.0) 4 (6.7)
9 (15.0)
6 (10.0) Metal 45°C
Pain intensity t1
t2
t3 60
60
60 0
0
0 10
9
8 1.4 (±2.3)
1.8 (±2.5)
2.3 (±2.7) 24 (40)
28 (46.7)
30 (50.0) Mechanical parameters Q-tip
Perception intensity t1
t2
t3 60
60
60 0
0
0 20
20
20 10 (±5.6)
9.8 (±5.4)
9.4 (±5.2) 37 (61.7)
41 (68.3)
38 (63.3) CMS 0.7 mm
Pain intensity t1
t2
t3 60
60
60 0
0
0 10
9
10 2.4 (±2.2)
2.3 (±2.1)
2.7 (±2.6) 49 (81.7)
48 (80.0)
51 (85.0) Neurotip
Pain intensity t1
t2
t3 56†
56†
56† 0
0
0 10
9
10 2.3 (±2.2)
2.4 (±2.3)
2.9 (±2.7) 44 (78.6)
45 (80.4)
47 (83.9) Neuropen monofilament
Perception intensity t1
t2
t3 56†
56†
56† — — — 43 (71.7)
45 (80.4)
46 (82.1) von Frey hair 64 mN
Perception intensity t1
t2
t3 60
60
60 — — — 49 (81.7)
52 (86.7)
47 (78.3) Q-tip allodynia
Pain intensity t1
t2
t3 60
60
60 0
0
0 6
9
8 0.8 (±1.7)
0.7 (±1.7)
1.0 (±2.0) 15 (25.0)
12 (20.0)
18 (30.0) Q-tip postallodynia sensation
Pain intensity t1
t2
t3 60
60
60 0
0
0 9
8
8 1.1 (±2.0)
1.4 (±2.2)
1.4 (±2.2) 20 (33.3)
21 (35.0)
24 (40.0) CMS 0.7 mm WUR single stimulus
Pain intensity t1
t2
t3 56
56
56 0
0
0 8
7
10 2.0 (±1.8)
2.1 (±1.7)
2.3 (±2.4) — CMS 0.7 mm WUR series stimuli
Pain intensity t1
t2
t3 56
56
56 0
0
0 10
10
10 3.7 (±2.9)
4.3 (±3.1)
4.4 (±3.0) — CMS 0.7 mm WUR ratio (series/single stimulus) t1
t2
t3 46‡
46‡
46‡ 1
0.5
1 5
6
7 2.1 (±0.9)
2.2 (±1.1)
2.4 (±1.5) 40 (87.0)
41 (89.1)
40 (87.0) Neurotip WUR single stimulus
Pain intensity t1
t2
t3 56†
56†
56† 0
0
0 8
10
10 1.9 (±1.9)
2.1 (±1.9)
2.6 (±2.6) — Neurotip WUR series stimuli
Pain intensity t1
t2
t3 56†
56†
56† 0
0
0 10
10
10 4.3 (±3.0)
4.6 (±2.9)
5.1 (±3.1) — Neurotip WUR ratio (series/single stimulus) t1
t2
t3 44‡
45‡
50‡ 1
1
1 7
5
8 2.8 (±1.4)
2.6 (±1.1)
2.7 (±1.9) 43 (97.7)
44 (97.8)
45 (90.0) Vibration detection threshold t1
t2
t3 60
60
60 0
0
0 8
8
8 4.9 (±2.5)
5.0 (±2.4)
4.7 (±2.6) — Pressure algometer at 4 mL
Pain intensity t1
t2
t3 60
60
60 0
0
0 10
10
10 3.0 (±3.4)
3.5 (±3.5)
3.2 (±3.4) 35 (58.3)
40 (66.7)
38 (63.3) Pressure algometer
Pain pressure threshold t1
t2
t3 60
60
60 2
2
1.5 10
10
10 4.1 (±2.0)
4.5 (±2.0)
4.3 (±2.1) —

Displayed are the number of data sets (n), the minimum (Min), the maximum (Max) ratings, the mean and corresponding standard deviation (mean ± SD), and the percentage of perceived/painful stimuli (detection rate [%]) for all 3 study visits (t1, t2, t3).

*While for the interval-scaled parameters only n = 59 patient data were available, n = 60 patient data could be included for the dichotomized parameters.

†Note tha