Flare and Itch Induced by Substance P in Human Skin

126

1 Applications of capsaicin, nicotine and methacholine were made locally onto the nasal mucosa in human controls and patients suffering from hyperreactive nasal disorders. Perception of sensation was registered as a sympton score and secretion quantified. The sensory reaction (irritationpain) to capsaicin was similar in the three groups studied, i.e. controls, a group of patients with the diagnosis of vasomotor rhinitis and a group of patients with increased nasal secretion as the main symptom of the hyperreactive disorder. Nicotine induced only a mild itching sensation in the three groups. However, capsaicin and nicotine challenge caused a significantly larger secretory response in the last group than in the unselected vasomotor rhinitis group and in the control group. 2 Pretreatment with muscarinic receptor antagonists almost completely abolished the secretory response to both capsaicin and nicotine, and blocked methacholine-induced secretion. Furthermore, pretreatment with a combination of local anaesthetic and vasoconstrictor agent abolished the capsaicin-induced irritation, as well as the capsaicin-and nicotine-induced secretion on both the ipsilateral and the contralateral side. Therefore, no clearcut contribution seems to be exerted by locally released peptides from sensory neurones as direct trigger substances for the secretory response to capsaicin. 3 In conclusion, the nasal secretory response, in man, to both capsaicin and nicotine, seems to be mediated via cholinergic parasympathetic reflexes. In patients with hyperreactive non-allergic disorders of the nasal mucosa with rhinorrhea as the main complaint, the enhanced secretion may be due to a hyperreactive efferent cholinergic mechanism rather than hypersensitive irritant receptors on capsaicin-and nicotine-sensitive sensory neurones. Challenge with irritant agents seems a useful test for the evaluation of both afferent and efferent reflexogenic responses in hyperreactive disorders of the nasal mucosa.

Section: Resultsmentioning

confidence: 99%

Capsaicin and nicotine‐sensitive afferent neurones and nasal secretion in healthy human volunteers and in patients with vasomotor rhinitis

Stjärne

Lundblad

Lundberg

et al. 1989

126

“…The activities of substance P-related peptides as histamine releasers in rat mast cells is correlated with their activity in producing flare responses in human skin (Foreman & Jordan, 1981) and there is evidence that the flare response to intradermal injection of substance P is mediated by histamine release from skin mast cells (Hagermark et al, 1978;Foreman & Jordan, 1981). We have shown in this study that neurotensin produces flare, and also wheal responses, when injected intradermally into human skin, but it is less potent than substance P in these respects.…”

Section: Discussionmentioning

confidence: 99%

“…Immunohistochemical and neurochemical evidence indicates that substance P is present in the peripheral as well as the central terminals of some primary afferent neurones (Hokfelt, Kellerth, Nilsson & Pemow, 1975; Cuello, Del Fiacco & Paxinos, 1978) and it is conceivable, therefore, that substance P is released from these neurones in the skin and other organs. It has been proposed that substance P, released from sensory nerve endings, plays a part in the triple response of skin to an injury (Hagermark et al, 1978;), and we have already pointed out that the flare, which is believed to be mediated by the so-called 'axon reflex' in the triple response, is induced only by those peptides which also release histamine from rat mast cells in vitro (Foreman & Jordan, 1981). The relationship between substance P and mast cells in injury and inflammation is thus of interest, and inhibitors of the peripheral actions of substance P might have a suppressant effect on some inflammatory reactions.…”

Section: Introductionmentioning

confidence: 99%

“…Intradermal injection of the undecapeptide, substance P (Figure 1) produces a wheal and flare reaction in man (Hagermark, Hokfelt & Pernow, 1978;Foreman & Jordan, 1981) and it is known that this peptide also releases histamine from mast cells (Johnson & Erdos, 1973; Kitada, Ashida, Maki, Fujimo, Hirai, Yasuhara, Nakajima, Takeyama, Koyama & Yajima, 1980;Erjavec, Lembeck, Florjanc-Irman, Skofitsch, Donnerer, Saria & Holzer, 1981;Fewtrell, Foreman, Jordan, Oehme, Renner & Stewart, 1982). Immunohistochemical and neurochemical evidence indicates that substance P is present in the peripheral as well as the central terminals of some primary afferent neurones (Hokfelt, Kellerth, Nilsson & Pemow, 1975; Cuello, Del Fiacco & Paxinos, 1978) and it is conceivable, therefore, that substance P is released from these neurones in the skin and other organs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interaction of Neurotensin With the Substance P Receptor Mediating Histamine Release From Rat Mast Cells and the Flare in Human Skin

Foreman

Jordan

Piotrowski

1982

1 Substance P induced histamine release from rat peritoneal mast cells in a dose-dependent manner over the concentration range 1 to 10 DIM.2 At concentrations in the range 2.5 to 10 EM, neurotensin produced only about 5% release of histamine, which was substantially less than the maximum effect obtained with substance P. 3 Neurotensin,2.5 to 10 lM produced graded inhibition of histamine release induced by substance P. The inhibitory effect of neurotensin was not seen when histamine release was induced by an antigen-antibody reaction or by the ionophore, A 23187. Some evidence was obtained to suggest that compound 48/80 may interact with the same receptor as substance P and neurotensin. [D-Arg8]neurotensin, [D-Arg9]neurotensin, xenopsin and the C-terminal octapeptide of substance P (SP411) all inhibited histamine release by substance P, but physalaemin did not.5 Neurotensin inhibited the wheal and flare reactions induced by substance P in human skin.6 [D-Trp7'9]substance P released histamine from rat mast cells and was about 12 times more potent than substance P itself. [D-Trp7'9]SP1_1j also produced wheal and flare responses in human skin, being 1.8 times more potent than substance P in the production of flare.

“…The axon reflex flare (vasodilatation) follows intradermal injection of histamine (Lewis, 1927) and substance P (SP) (Hagermark, Hokfelt & Pernow, 1978) in human skin, and is inhibited by topical capsaicin pretreatment (Carpenter & Lynn, 1981;Bernstein, Swift, Soltani & Lorincz, 1981). It has been postulated that axon reflex flare is produced by release of SP from nociceptive sensory afferent terminals in the skin (Burnstock, 1977;Henry, 1977), and it has been demonstrated that SP is released from the central terminals of such nociceptive fibres (Nicoll, Schenker & Leeman, 1980).…”

Section: Introductionmentioning

confidence: 99%

Topical capsaicin pretreatment inhibits axon reflex vasodilatation caused by somatostatin and vasoactive intestinal polypeptide in human skin

Anand

Bloom

McGregor

1983

Wheal and flare reactions are described following intradermal injections of somatostatin, vasoactive intestinal polypeptide, substance P and histamine in normal human forearm skin. Bombesin failed to produce a significant wheal and flare. Pretreatment of skin with capsaicin in all cases dramatically inhibited the flare but not the wheal. This result is in accord with the hypothesis that capsaicin blocks the effector side of the axon reflex, perhaps by depleting nerve terminals of vasodilatory peptide(s).