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Objective: To compare simple tests of small nerve fibre function with intraepidermal nerve fibre density (IENFD) in the evaluation of small fibre neuropathy (SFN). Methods: Patients with idiopathic SFN of the hands were prospectively studied. Evaluation involved clinical examination, nerve conduction studies, sympathetic skin response (SSR) and skin wrinkling stimulated by water and EMLA (eutectic mixture of local anaesthetics). Results: Of 21 patients, 16 (76%) had low IENFD, 15 (71%) impaired water-induced wrinkling, 14 (67%) impaired EMLA-induced wrinkling, and nine (43%) abnormal SSR. Conclusions: Stimulated skin wrinkling was nearly as sensitive as IENFD in diagnosing SFN, whereas SSR was of less use. Stimulated skin wrinkling is a useful supportive test when IENFD or other tests of small nerve fibre function are not available.

The underlying mechanism of the water-immersion skin wrinkling test, which is used as a test of sympathetic nerve function, remains elusive. We investigated changes of blood circulation in the hand occurring with water-immersion wrinkling by measuring the velocity of ulnar and digital artery blood flow, and of digit skin blood flow, in healthy subjects before and during wrinkling. Wrinkling was accompanied by significant reduction in blood flow velocity in all vessels, with a maximum in digital vessels. Our data show that water-immersion wrinkling is a function of digit pulp vasoconstriction. This test of sympathetic function can now be quantified using parameters of blood flow velocity, enabling its more widespread and accurate use.

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Epidermal transient receptor potential vanilloid 1 in idiopathic small nerve fibre disease, diabetic neuropathy and healthy human subjects Aims: The transient receptor potential vanilloid 1 (TRPV1) plays an important role in mediating pain and heat. In painful neuropathies, intraepidermal TRPV1 nerve fibre expression is low or absent, suggesting that pain generated is not directly related to sensory nerve fibres. Recent evidence suggests that keratinocytes may act as thermal receptors via TRPV1. The aim was to investigate epidermal TRPV1 expression in patients with neuropathic conditions associated with pain. Methods and results: In a prospective study of distal small nerve fibre neuropathy (DISN; n = 13) and diabetic neuropathy (DN; n = 12) intraepidermal nerve fibre density was assessed using the pan axonal marker PGP 9.5 and epidermal TPVR1 immunoreactivity compared with controls (n = 9). Intraepidermal nerve fibres failed to show TRPV1 immunoreactivity across all groups. There was moderate and strong TRPV1 reactivity of epidermal keratinocytes in 41.8% and 6% for DISN, 32.9% and 2.9% for DN and 25.4% and 5.1% for controls, respectively. Moderate keratinocyte TRPV1 expression was significantly increased in DISN compared with controls (P = 0.01). Conclusion: Our study suggests that in human painful neuropathies, epidermal TRPV1 expression is mainly in keratinocytes.