The actions of capsaicin applied topically to the skin of the rat on C‐fibre afferents, antidromic vasodilatation and substance P levels

Abstract

1Single 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 > 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 I 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.

Profile of capsaicin‐induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid‐induced ear oedema

“…The topical application of capsaicin to rat skin leads to excitation of afferent neurones (Kenins, 1982), increases in skin blood flow (Jancso, 1968), and vasodilatation (Lynn et al, 1992). In our experiment, the capsaicin-treated mouse ear became erythematous and oedematous, reaching a maximum effect at 30 min.…”

Involvement of substance P as a mediator in capsaicin-induced mouse ear oedema

“…Topical application of capsaicin to rat skin leads to excitation of afferent neurones [2], Correspondence to." H. Inoue vasodilation [3], and increases in skin blood flow [4]. With repeated treatment, these effects diminish or disappear, and there is a reduction of the vasodilator flare around localized skin injuries [5][6][7].…”

Topical and Peripherally Acting Analgesics

“…Both desensitization and neurotoxicity lead to analgesia in rodent paradigms, with specific characteristics of analgesia depending on the dose of capsaicin, route of administration, treatment paradigm (i.e., acute or repeated administration), and age of the animal (Holzer, 1991;Winter et al, 1995). The topical skin application of capsaicin to rodents produces analgesia (Kenins, 1982;Lynn et al, 1992), but variability in outcome can occur due to the concentration, the number of applications, and the different vehicles used that can affect the rate and extent of skin penetration (Carter and Francis, 1991;McMahon et al, 1991).…”