Small fibre pathology in chronic whiplash‐associated disorder: A cross‐sectional study

Abstract

Background Mechanisms underpinning ongoing symptoms in chronic whiplash associated‐disorder (WAD) are not well understood. People with chronic WAD can exhibit sensory dysfunction consistent with small nerve fibre pathology, including thermal hypoaesthesia and hyperalgesia. This study investigated small fibre structure and function in chronic WAD. Methods Twenty‐four people with chronic WAD (median [IQR] age 49 [15] years, 16 females) and 24 pain‐free controls (50 [17] years, 16 females) were recruited. Intraepidermal nerve fibre density (IENFD) and dermal innervation were assessed by skin biopsy. This was performed at (a) the lateral index finger on the primary side of pain and (b) superior to the lateral malleolus on the contralateral side. Quantitative sensory testing was performed over the hand. Results The WAD group exhibited lower IENFD at the finger (WAD: median [IQR] 4.5 [4.9] fibres/mm; control 7.3 [3.9]; p = .010), but not the ankle (WAD: mean [SD] 7.3 [3.7] fibres/mm; control 9.3 [3.8]; p = .09). Dermal innervation was lower in the WAD group at the finger (WAD: median [IQR] 3.7 [2.8] nerve bundles/mm2; controls: 4.9 [2.1]; p = .017) but not the ankle (WAD: median [IQR] 2.1 [1.9] nerve bundles/mm2; controls: 1.8 [1.8]; p = .70). In the WAD group, hand thermal and light touch detection were impaired, and heat pain thresholds were lowered (p ≤ .037). Conclusions Findings suggest small fibre structural and functional deficits in chronic WAD, implicating potential involvement of small fibre pathology. Significance Our study found decreased intraepidermal nerve fibre density, reduced dermal innervation, thermal hypoaesthesia and hypersensitivity in people with chronic WAD, suggestive of small fibre pathology. This observation of peripheral nervous system pathology in chronic whiplash provides novel insights on mechanisms underpinning symptoms and challenges commonly held beliefs regarding this condition.

Are Reports of Pain, Disability, Quality of Life, Psychological Factors, and Central Sensitization Related to Outcomes of Quantitative Sensory Testing in Patients Suffering From Chronic Whiplash Associated Disorders?

“…116 The TS effect did not differ between both groups, indicating no differences in endogenous pain facilitation. This finding is in line with several other studies that compared TS between CWAD patients and healthy controls, [117][118][119] but contradicts 1 other study that did obtain significant differences in constant cuff pressure-based TS. 119 Interestingly, although the individuals with CWAD included received stimuli at a lower intensity (at the intensity of the EPT), these individuals with CWAD systematically scored the stimuli as being more painful than the PFCs.…”

Nerve pathology and neuropathic pain after whiplash injury: a systematic review and meta-analysis

“…43 Finally, a significant decrease in intraepidermal nerve fibre and dermal nerve bundle densities was apparent in skin biopsies of the index finger compared with controls. 31…”

“…Using the S-LANSS, the mean prevalence scores indicating the presence of neuropathic pain characteristics were 34% (range 25%-36%, n 5 123) in WAD II. 31,42,90 One study used the NPSI and reported a mean (SD) of 26.1 (18.3) of 100 (n 5 24). 31 Using the IASP neuropathic pain grading system, 2 of the 8 studies (25%) had sufficient tests to reach the grade of definite neuropathic pain in at least a subgroup of patients.…”

“…31,42,90 One study used the NPSI and reported a mean (SD) of 26.1 (18.3) of 100 (n 5 24). 31 Using the IASP neuropathic pain grading system, 2 of the 8 studies (25%) had sufficient tests to reach the grade of definite neuropathic pain in at least a subgroup of patients. Results from 3 studies (38%) reached a grade of probable neuropathic pain, and another 3 studies (38%) could reach a grade of possible neuropathic pain.…”

“…Overall, there were significantly impaired vibration detection thresholds at the thumb (SMD 0.55 [0.05; 1.06] P 5 0.0422, I 2 5 0%) and index finger (SMD 0.71 As previously reported, one study including only WAD II found a significant reduction in mechanical detection using von Frey hairs but preserved mechanical pain at the index finger compared with controls. 31…”