Effect of topical capsaicin on the cutaneous responses to inflammatory mediators and to antigen in man

The Possible Role of Substance P in the Allergic Reaction, Based on Two Different Provocation Models

“…Several ef fects of SP have been shown in vitro and in vivo. It has been demonstrated that SP stimulated human T lymphocyte proliferation, indicating a new approach for the regulation of local immunologic activity by sensory nerves [4], Neuroimmune interactions within the human skin have also been demonstrated by hista mine, prostaglandin D2 and leukotriene C4 release from skin mast cells after SP stimulation [6], Capsai cin pretreatment (depletion of sensory nerves from neuropeptides) caused an inhibition of the immediate Hare response to histamine and platelet-activating factor (not for prostaglandin E2 and antigen), indicat ing that the cutaneous vasodilator effect is mediated by a local axon reflex with release of neuropep tides [7].…”

Peptidergic sensory neurons in the control of vascular functions: Mechanisms and significance in the cutaneous and splanchnic vascular beds

“…It is, therefore, conceivable that sensitized afferent neurons enhance host defence reactions to injurious stimuli by a direct stimulant action on immunocompetent cells and by way of hyperaemia and increased vascular permeability which facilitate the delivery and accumulation of these cells in the inflamed tissue. In line with this proposal, antigen exposure has been lbund to increase nerve activity in afferent neurons (Undem et al 1991), whilst the vascular reactions of the skin to allergen challenge in sensitized guinea pigs ) and allergic humans (Lundblad et al 1987;Wallengren and M/311er 1988;McCusker et al 1989;Wallengren 1991), and the vascular manifestations of acquired cold and heat urticaria (T6th-K~isa et ) are reduced after blockade of capsaicin-sensitive afferent nerve fibres or administration of an SP antagonist. Hyperreactive disorders of the skin such as psoriasis (Bernstein et Farber et al 1986), bullous pemphigoid, eczema and photodermatoses (Wallengren et al 1986) may also involve peptidergic afferent neurons.…”

“…To put these findings into proper pathophysiological perspective, it needs to be considered that capsaicin-sensitive afferent neurons represent probes that monitor a variety of potentially harmful chemicals including hydrochloric acid (Clarke and Davison 1978;Cervero and McRitchie 1982;Martling and Lundberg 1988;Forster et al 1990;Bevan and Yeats 1991;Geppetti et al 1991;Holzer et al 1991a;Takeuchi et al 1991b;Holzer and Lippe 1992;Steen et al 1992), acetic acid (Leung 1992b), hypertonicity (Forster et al 1990;Matsumoto et al 1991b;Tramontana et al 1991), the bacterial peptide Nformyl-methionyl-leucyl-phenylalanine , platelet-activating factor (Rodrigue et McCusker et al 1989;Pique et al 1990; Sestini et at. 1990;Spina et al 1991), endothelin-1 (Whittle and Lopez-Belmonte 1991) and other factors such as prostanoids, leukotrienes and bradykinin (see Maggi 1991;Rang et al 1991).…”

Cutaneous Drug Delivery of Capsaicin after in vitro Administration of the 8% Capsaicin Dermal Patch System

“…The distribution of expression of TRPV1 in the skin indicates that both the vital epidermis and the dermis are to be the designated microcompartments for capsaicin [35]. TRPV1 is expressed by keratinocytes in the epidermis as well as by fibroblasts, endothelial cells and immunocompetent cells in the dermis [7,14]. However, of main relevance in the context of analgesic effects is the anatomic fitting of the skin layers especially with C and Aδ pain fibres, which are established in the dermis but grow into the vital epidermis [59,60].…”

“…TRPV1 can also be detected in different extracutaneous organs (i.e. central nervous system, bronchial and kidney epithelia) as well as in effector cells of the immune system [14]. Apart from capsaicinoids, physical triggers like heat (≥43°C), an acidic environment (pH <6) or changes in the membrane potential can activate the receptor (fig.…”