CUTANEOUS RESPONSES TO ENDOTHELIN-1 AND HISTAMINE IN PATIENTS WITH VIBRATION WHITE FINGER

Vibration white finger (VWF) is the episodic blanching of the fingers that occurs in response to cold in those who work with hand-held vibra ting tools, Clinically the condition differs from primary Raynaud's ph enomenon as persistent pain and paresthesia are common in the hands an d arms and occur independently of the ''white attacks.'' We have previ ously reported a decrease in protein gene product 9.5 and calcitonin g ene-related peptide-immunoreactive nerve fibers in the digital skin of individuals with VWF, In this study, we have sought to determine whet her this deficit of immunoreactive sensory-motor nerves has a function al counterpart in vivo. Histamine produces a rapid wheal and flare res ponse following intradermal injection, whereas endothelin-l (ET-1) pro duces a central area of pallor with a surrounding neurogenic flare, In contrast, calcitonin gene-related peptide produces a non-neurogenic e rythema, In this study, histamine and ET-1 were injected into the dors um of the middle phalanx and the local neurovascular response was asse ssed by measuring the area of the visible flare or pallor. Basal finge r blood flow was also measured by laser Doppler flowmetry in each of t he digits prior to intradermal injection, The experiments were perform ed at 21 degrees C and 4 degrees C. Patients with VWF and asymptomatic vibration-exposed workers had significantly lower resting skin blood flow at both 21 degrees C and 4 degrees C than heavy manual workers wi th no vibration exposure, The size of the histamine- and ET-1-induced flares at both 21 degrees C and 4 degrees C was significantly smaller in patients with VWF when compared with the asymptomatic vibration-exp osed workers and heavy manual workers, The size of the ET-l-induced pa llor was smaller in patients with VWF when compared with the heavy man ual workers at both 21 degrees C and 4 degrees C. In contrast, the are a of erythema induced by intradermal injection of calcitonin gene-rela ted peptide at both 21 degrees C and 4 degrees C was of a similar size in patients with VWF and in heavy manual workers, These results indic ate that the neuroneal deficit identified by immunohistochemistry in t he digital skin of patients with VWF has a functional counterpart in v ivo and is evident as a reduced ability to propagate an axon-reflex va sodilator response when challenged with histamine and ET-1, Furthermor e, these results enable patients with VWF to be differentiated from bo th asymptomatic vibration-exposed workers, in whom the histamine-and E T-1-induced flares are normal, and those with primary Raynaud's diseas e, in whom the ET-1 hare is reduced and the histamine-induced flare is normal.