Role of C-nociceptive fibers in the nerve axon reflex-related vasodilation in diabetes.
OBJECTIVE
To evaluate the role of the C-nociceptive nerve fibers in nerve axon reflex-related vasodilation.


METHODS
Skin vascular reactivity, in response to iontophoresis of acetylcholine and sodium nitroprusside, was evaluated at both the forearm and the foot levels in 13 diabetic neuropathic (DN),11 nonneuropathic (D), and 9 healthy control (C) subjects. The total and nerve axon reflex-related vasodilation were measured by two single-point laser probes. A topical anesthetic was applied on the contralateral forearm and foot, and all the measurements were repeated.


RESULTS
Dermal anesthesia resulted in a reduction of the nerve axon reflex-related vasodilation at the forearm in all three groups (C 70.7 +/- 12%, D 59.7 +/- 7%, and DN 73.5 +/- 14%; percentage of reduction over preanesthesia response, mean +/- SEM; p < 0.001) and at the foot in the two nonneuropathic groups (C 74 +/- 10% and D 68.9 +/- 9%; p < 0.001 versus before anesthesia). This reduction was absent at the foot of the neuropathic patients (DN -4 +/- 21%; p = NS versus before anesthesia). A correlation was found between the nerve axon reflex-related response and measurements of nerve function (neuropathy disability score, r = -0.425, p < 0.017; vibration perception threshold, r = -0.527, p < 0.002; Semmes-Weinstein monofilament perception, r = -0.619, p < 0.001).


CONCLUSIONS
The nerve axon reflex-related vasodilation is directly related to the function of the C-nociceptive fibers and is significantly associated with other nerve function measurements. As this is an objective measurement, it has the potential to be used as an alternative to currently employed techniques to evaluate small-fiber function.
Caselli
A
A
Joslin-Beth Israel Deaconess Foot Center, Department of Surgery, Microcirculation Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Rich
J
J
Hanane
T
T
Uccioli
L
L
Veves
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D001369:Axons; D001783:Blood Flow Velocity / Q000187:drug effects; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D005260:Female; D005528:Foot / Q000098:blood supply / Q000294:innervation / Q000503:physiopathology; D005542:Forearm / Q000098:blood supply / Q000294:innervation / Q000503:physiopathology; D006801:Humans; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D012016:Reference Values; D012018:Reflex / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000294:innervation / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000779:Anesthetics, Local; D000109:Acetylcholine