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Peripheral Autonomic Neuropathy and Axon Reflex

When a stimulus causes backward nerve transmission, vasodilation of the innervated blood vessels occurs; this is the axon reflex, also referred to as the flare response. An impaired axon reflex indicates peripheral neuropathy.

In practical terms, when skin is heated (by using the moorVMS-HEAT) or iontophoresed (by using the MIC2) with acetylcholine over a well defined area, microvascular blood flow also increases in the surrounding skin (as well as at the site stimulated). Laser Doppler monitoring (moorVMS-LDF) is used to assess magnitude and time course of the vasodilation, and additional information on the flare area can be obtained with laser Doppler (moorLDI2) and Speckle imaging (moorFLPI).

Examples of use

Small fibre neuropathies : Krishnan et al (2004) have use skin heating to evoke a flare response and assessed flare area with laser Doppler imaging; they concluded that their test demonstrated C-fibre dysfunction in type 2 diabetes before other currently available methods.

Small Fibre Neuropathies have been shown to produce a reduction in flare area but not maximal LD response to histamine (Bickel et al, 2002).

Inhibition of Histamine Flare by iontophoresis of necrodomil sodium has been shown by Ahluwalia et al, 2001.

‘Reflex Sympathetic Dystrophy’; axon reflex vasodilation to iontophoresis of acetylcholine was impaired in the painful limb compared with the non-affected limb (Westerman et al, 1992).

Local Anaesthesia reduces the axon reflex flare to iontophoresis of acetylcholine chloride (Caselli et al, 2003).


Ahluwalia P, McGill J I, Church M K. Nedocromil sodium inhibits histamine-induced itch and flare in human skin. British Journal of Pharmacology. 2001, 132, 613-616.

Bickel A; Kramer H H; Hilz M J; Birklein F; Neundorfer B, and Schmelz M. Assessment of the neurogenic flare reaction in small-fiber neuropathies. Neurology 2002; 59, 917-919.

Caselli A, Rich J, Hanane T, Uccioli L, and Veves A. Role of C-nociceptive fibers in the nerve axon reflex-related vasodilation in diabetes. Neurology 2003: 60, 297-300.

Krishnan STM and Rayman G. The LDIflare: A novel test of C-fiber function demonstrates early neuropathy in type 2 diabetes. Diabetes Care 27:2930–2935, 2004.

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