Small fibre pathology, small fibre symptoms and pain in fibromyalgia syndrome

Abstract

A proportion of people with fibromyalgia demonstrate small fibre pathology (SFP). However, it is unclear how SFP directly relates to pain phenomenology. Thirty-three individuals with FMS and ten healthy volunteers underwent assessment of SFP and sensory phenotyping using corneal confocal microscopy, validated questionnaires and quantitative sensory testing (QST). Corneal nerve fibre length was used to stratify participants with fibromyalgia into with SFP [SFP+] and without SFP [SFP-]. SFP was detected in 50% of the fibromyalgia cohort. Current pain score and QST parameters did not differ between SFP+ and SFP-. Mechanical pain sensitivity (MPS) demonstrated a significant gain-of-function in the SFP- cohort compared to healthy-volunteers (p = 0.014, F = 4.806, η² = 0.22). Further stratification revealed a cohort without structural SFP but with symptoms compatible with small fibre neuropathy symptoms and a significant gain in function in MPS (p = 0.020 Chi-square). Additionally, this cohort reported higher scores for both depression (p = 0.039, H = 8.483, η² = 0.312) and anxiety (p = 0.022, F = 3.587, η² = 0.293). This study confirms that SFP is present in a proportion of people with fibromyalgia. We also show that in a proportion of people with fibromyalgia, small fibre neuropathy symptoms are present in the absence of structural SFP. Greater mechanical pain sensitivity, depression and anxiety are seen in these individuals.

Figure 1

Sensory profiles. (A) Individual and group mean ± SD of z-scores for thermal quantitative sensory testing parameters in patients with FMS without (purple hollow circles) and with (pink circles) SFP based on CCM assessment and control subjects (dark blue triangles). (B) Individual and group mean ± SD of z-scores for mechanical quantitative sensory testing parameters in patients with FMS without (purple hollow circles) and with (pink circles) SFP based on CCM assessment and control subjects (dark blue triangles). One-way ANOVA and Tukey’s multiple comparison test for parametric data and Kruskal–Wallis test and Dunn’s multiple comparison test for non-parametric data; *p ≤ 0.05. CDT cold detection threshold, WDT warm detection threshold, TSL thermal sensory limen, CPT cold pain threshold, HPT heat pain threshold, MDT mechanical detection threshold, VDT vibration detection threshold, MPT mechanical pain threshold, MPS mechanical pain sensitivity, WUR wind-up ratio, PPT pressure pain threshold.

Figure 2

Small fibre neuropathy screening list complaints in patients with fibromyalgia. (A) Small fibre neuropathy symptom frequency in FMS patients without (purple) and with (pink) SFP on CCM assessment. (B) Small fibre neuropathy symptom severity in FMS patients without (purple) and with (pink) SFP on CCM assessment. Bar height represents the overall percentage of patients experiencing the complaint. Bar shading represents the proportion of patients experiencing the complaint sometimes/always/often/always and with severity slightly/variably/moderately/seriously. The darkness of shading increases with increasing frequency and severity of symptoms.

Figure 3

CCM raw images. Representative CCM images from patients with FMS (A) with SFP and (B) without SFP compared to (C) control subject; (380 × 380 pixels with an area of 400 × 400 mm²).

Figure 4

Corneal confocal microscopy parameters. Individual and group mean of CNFL, CNFD, and CNBD in patients with FMS without (purple hollow circles) and with (pink circles) SFP and control subjects (dark blue triangles). One-way ANOVA and Tukey’s multiple comparison test ***p ≤ 0.001. CNFL corneal nerve fibre length, CNFD corneal nerve fibre density, CNBD corneal nerve branch density.

Figure 5

Individual patient phenotypes. 4 patient groups based on CNFL (SFP−/SFP+) and Small Fibre Neuropathy Screening List (SFNSL−/SFNSL+). Each column represents results from a single patient: normal (white) and abnormal (coloured). QST, gain of function is depicted with darker shade and loss of function is represented with lighter shade. PainDetect, negative (white) unclear (light grey) positive neuropathic pain (dark grey). FIQR, mild FMS symptoms (light shade), moderate FMS symptoms (mid shade), severe FMS symptoms (dark shade).

Figure 6

Pain, depression and anxiety. Individual current VAS pain, total PainDetect, FIQR depression and FIQR anxiety scores in patients with FMS: SFP−/SFNSL− (green circles); SFP−/SFNSL+ (orange circles); SFP+/SFNSL− (blue circles); SFP+/SFNSL+ (yellow circles). The centre line denotes the median value. One-way ANOVA and Tukey’s multiple comparison test for parametric data and Kruskal–Wallis test and Dunn’s multiple comparison test for non-parametric data; *p ≤ 0.05, **p ≤ 0.01.