The actions of capsaicin applied topically to the skin of the rat on C-fibre afferents, antidromic vasodilatation and substance P levels.
1. Single applications of solutions of capsaicin were made to the intact skin of anaesthetized rats and the effects on cutaneous blood flow and the firing of C-nociceptor afferents determined. Blood flow was measured by laser-Doppler flowmetry. C-fibre activity was recorded from filaments dissected from the saphenous nerve. 2. Following the application of a capsaicin solution (concentration > or = 1 mM) to rat saphenous skin, low frequency firing occurred in C-polymodal nociceptors that sometimes continued for > 10 min. At the some time, large increases in skin blood flow occurred exceeding 300% in some instances. 3. After the initial excitation, some C-polymodal nociceptors lost their sensitivity to pressure whilst their sensitivity to heat was lost or enhanced depending on the vehicle used. 4. Sensitivity of C-polymodal nociceptors to heat recovered in < 1 day following a single application of 33 mM capsaicin. Thresholds to mechanical pressure, however, were still significantly elevated by 123% on day 1, but had recovered on day 2. 5. Vasodilatation in response to saphenous nerve stimulation ('antidromic vasodilatation') was significantly reduced by 35%, 2 days after a single application of 33 mM capsaicin, but was normal at 4 days. 6. Following a single application of 33 mM capsaicin, skin substance P levels fell to only half the normal value at day 1 and remained at this level throughout the 4 day period examined. 7. It is suggested that the ability of relatively low concentrations of capsaicin to desensitize C-fibre nociceptors may underlie the analgesic action of topical capsaicin in man.
Lynn
B
B
Department of Physiology, University College London.
Ye
W
W
Cotsell
B
B
D000287:Administration, Topical; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D017078:Laser-Doppler Flowmetry; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation; D013373:Substance P / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*
D013373:Substance P; D002211:Capsaicin