An investigation into the mechanism of capsaicin-induced oedema in rabbit skin.
1. Oedema formation induced by intradermal capsaicin has been studied in rabbit skin. The effect of the anti-inflammatory steroid dexamethasone and also of a range of known inhibitors of oedema formation have been investigated in order to elucidate mechanisms involved in capsaicin-induced oedema formation. 2. Oedema formation, in response to intradermally-injected test agents, was measured by the local extravascular accumulation of intravenously injected 125I-labelled albumin. In separate experiments skin blood flow was assessed by the clearance of intradermally-injected 133xenon. 3. Oedema formation induced by intradermal histamine (3 nmol) and bradykinin (1 nmol), when in the presence of vasodilator doses of calcitonin gene-related peptide (CGRP) (3 pmol) or prostaglandin E1, (PGE1) (10 pmol), was significantly inhibited (P < 0.01) in rabbits pretreated with intravenous dexamethasone (3 mg kg-1, -4 h). In contrast dexamethasone had no effect on capsaicin (3 mumol)-induced oedema formation or, on capsaicin (30-100 nmol)-induced blood flow. 4. Oedema formation observed in response to intradermal capsaicin (3 mumol) was significantly inhibited (P < 0.01) when the selective capsaicin antagonist, ruthenium red (3 nmol) was co-injected. This suggests that the mechanism of capsaicin-induced oedema involves activation of sensory nerves. However, oedema was not inhibited when capsaicin was co-injected with the neurokinin NK1 receptor antagonist, RP67580 (10 nmol), the NK2 antagonist SR48960 (10 nmol) or the CGRP antagonist CGRP8-37 (300 pmol). 5. Oedema formation induced by capsaicin was not inhibited when co-injected with the histamine HI receptor antagonist, mepyramine (3 nmol), the PAF antagonist, WEB 2086 (100 nmol), the bradykinin B2 receptor antagonist, Hoel4O (1 nmol), or the cyclo-oxygenase inhibitor, indomethacin (10 nmol),suggesting that these mediators do not play a major role in the capsaicin-induced response.6. Histological analysis of capsaicin-treated skin sites revealed undamaged, intact microvessels and lack of haemorrhage. Further, co-injection of capsaicin with the hydrogen peroxide remover, catalase(2,200 u), had no effect on oedema formation. This suggests that capsaicin does not induce oedema formation secondary to free radical-induced damage.7. These results indicate that capsaicin-induced oedema in rabbit skin involves activation of sensory nerves. However, the oedema is not inhibited by pretreatment with the anti-inflammatory steroid,dexamethasone. Further the mechanisms which lead to the oedema formation observed after intradermal capsaicin remain unknown.
Newbold
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Pharmacology Group, King's College, London.
Brain
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D000527:Alprostadil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001920:Bradykinin / Q000008:administration & dosage / Q000633:toxicity; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D002199:Capillary Permeability / Q000187:drug effects; D002211:Capsaicin / Q000008:administration & dosage / Q000633:toxicity*; D002374:Catalase / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004347:Drug Interactions; D004487:Edema / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D006632:Histamine / Q000008:administration & dosage / Q000633:toxicity; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D054833:Isoindoles; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012430:Ruthenium Red / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D013373:Substance P / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001549:Benzamides; D007211:Indoles; D054833:Isoindoles; D010880:Piperidines; D014665:Vasodilator Agents; D012430:Ruthenium Red; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; C073839:SR 48968; D003907:Dexamethasone; D006632:Histamine; D002374:Catalase; D000527:Alprostadil; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D001920:Bradykinin; D007213:Indomethacin