Sensory changes and loss of intraepidermal nerve fibers in painful unilateral nerve injury

Abstract

Objectives: Dysaesthesias is a common symptom in patients with neuropathic pain after peripheral nerve injury (PNI). In contrast to neuropathies with comparable symptoms there is little knowledge of the underlying mechanisms in PNI patients.

Methods: Quantitative sensory testing according to the German Research Network on Neuropathic Pain protocol, and changes in intraepidermal nerve fiber density were assessed in 15 patients with dysaesthesias after PNI of the lower limb. According to their small-fiber function patients were assigned into 2 subgroups.

Results: The sensory profiles of PNI patients were characterized predominantly by minus symptoms (significantly increased thresholds for perception of cold, warm, touch and vibration, and significantly increased thresholds for heat and mechanical pain) on the affected compared with the unaffected side. The only plus symptom reported was a significantly reduced pressure pain threshold. The sensory profile of patients with a severe loss of small-fiber function (n=7) showed a thermal and tactile hypoaesthesia and hypoalgesia; this was in contrast to patients with a moderate loss of small-fiber function, who showed a mild thermal and tactile hypoaesthesia associated with an increased mechanical pain sensitivity. Mean intraepidermal nerve fiber density was significantly decreased in the affected compared with unaffected skin [3.50 (4.00) vs. 11.10 (7.60) fibers/mm] and correlated with warm and mechanical detection thresholds (both r=-0.60).

Discussion: In conclusion, even though patients presented with comparable clinical symptoms, their sensory profiles differed, supporting the concept of different underlying mechanisms leading to chronic pain in PNI patients. Skin biopsies support the validity of quantitative sensory testing.