Supplementary Table 1: Medication taken to relieve CTS symptoms No neuP Mild neuP Mod/sev neuP p-value Participants reporting analgesic drug use

Supplementary Table 1: Medication taken to relieve CTS symptoms

No neuP Mild neuP Mod/sev neuP

p-value

Participants reporting analgesic drug use^a

6 [28.6] 15 [28.8] ^$ 17 [53.1] 0.057°

Analgesics (e.g. Paracetamol) 3 [13.6] 6 [11.1] ^$ 13 [40.6] 0.004^∞ Nonsteroidal anti-

inflammatory drugs (NSAIDS)

3[13.6] 8 [14.8] 5 [15.6] 1.000^∞

Topical NSAIDS 1 [4.5] 3 [5.6] 0 [0.0] 0.422^∞

Antidepressants (e.g.

Tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors)

2 [9.1] 2 [3.7] 4 [12.5] 0.267^∞

Antiepileptics (e.g.

gabapentine, pregabalin)

1[4.5] 1 [1.9] 0 [0.0] 0.498^∞

Opioids 1 [4.5] 0 [0.0] ^$ 6 [18.8] 0.002^∞

Data are presented as median [IQR]. P-values reflect Chi-squared results° or Fisher´s exact test associations^∞ Significant Bonferroni adjusted Helmert contrasts are indicated by ^$ (mild versus moderate/severe neuP groups). Contrasts between no neuP versus combined neuP groups were not significant.

amultiple answers posible

Supplementary Table 2: The proportions of somatosensory profiles do not differ among groups

Data are presented as n [%].

No neuP Mild neuP Mod/sev neuP

neuP

Sensory loss 6 [27] 18 [33] 10 [31] 28 [33]

Thermal hyperalgesia 12 [55] 27 [50] 12 [38] 39 [45]

Mechanical hyperalgesia 4 [18] 9 [17] 10 [31] 19 [22]

Supplementary Table 3: Median nerve neurophysiology data of patients with CTS and healthy controls

Data are presented as median [IQR]. P-values reflect Kruskall Wallis test results.

Significant Bonferroni adjusted Helmert contrasts are indicated by *(healthy versus combined patient groups). No significant contrasts were found between no neuP versus combined neuP groups and mild versus moderate/severe neuP groups

Healthy No neuP Mild neuP Mod/sev neuP p-value

SNAP (µV) 12.9 [11.2]* 2.6 [9.7] 2.9 [7.4] 6.2 [8.3] <0.0001 Sensory nerve

conduction velocity (m/s)

49.4 [7.6]* 36.7 [9.4] 34.5 [8.4] 35.0 [6.1] <0.0001

Distal motor latency (ms)

3.2 [0.8]* 5.4 [1.7] 5.2 [2.1] 5.0 [1.0] <0.0001 CMAP (mV) 7.1 [3.9]* 5.0 [5.2] 5.6 [4.8] 5.9 [4.4] 0.606

Supplementary Table 4: Postoperative improvements in emotional wellbeing in the prospective sub-cohort of carpal tunnel syndrome patients (n=74). Patients’ emotional wellbeing was determined before as well as 6 months after carpal tunnel decompression surgery.

Data are shown as median [IQR]. P-values reflect Wilcoxon signed rank tests for paired comparisons.

Pre surgery Post surgery P-value

PCS total 8.0 [15.0] 3.0 [10.3] 0.002

Rumination 3.0 [7.0] 1.0 [4.0] 0.001 Magnification 1.0 [3.0] 0.0 [2.0] 0.007 Helplessness 3.0 [7.0] 1.0 [4.3] 0.006

DAPOS

Depression 6.0 [3.0] 5.0 [2.0] 0.008

Anxiety 3.0 [2.0] 3.0 [1.0] 0.198

Outlook 12.0 [3.0] 12.0 [6.0] 0.518

PASS-20

Total 18.0 [33.25] 10.5 [26.75] 0.012 Cognitive 9.0 [18.0] 6.0 [12.0] 0.001

Escape 4.0 [7.0] 2.0 [7.0] 0.287

Fear 1.0 [5.0] 0.0 [3.0] 0.153

Anxiety 0.0 [2.0] 0.0 [2.0] 0.866

Supplemental Figure 1: Electrodiagnostic test grade according to the Bland criteria revealed no differences between patient subgroups. Violin plots show median (black line) and first and third quantile (dotted lines).

Supplemental Figure 2: Immunohistochemical staining of skin. An abundance of intraepidermal nerve fibres is apparent in a healthy control participant (left, arrows), whereas the intraepidermal nerve fibre density is reduced in a patient with CTS. Red:

protein gene product, green: myelin basic protein, blue: DAPI.