Cutaneous reactions to intradermal prostaglandins

100

I The activity produced by intra-arterial bradykinin and prostaglandin El was investigated in multifibre strands dissected from the saphenous nerves of anaesthetized rats.2 Bradykinin (0.5-10 gg) alone produced little activity in nerve strands but produced considerable activity following a 10 min infusion, but not a single injection, of prostaglandin E1 (5-100 ng). 3 Prostaglandin E1 alone produced a few large height spikes but following several injections of bradykinin smaller height spikes were also produced by prostaglandin El. 4 It was concluded that the presence of a low concentration of prostaglandin E1 is required for bradykinin to manifest its action and that bradykinin and prostaglandin E1 are mutually potentiating in their effects on afferent nerve terminals. IntroducdonProstaglandin generation has now been shown to take place in many forms of damage to the skin (Greaves & S0ndergaard, 1970; Anggird & Jonsson, 1971). It was suggested by Ferreira (1972) that the prostaglandins sensitize 'pain' receptors to stimulation by other inflammatory mediators, and it has been widely accepted that inhibition of synthesis of prostaglandins constitutes the principal mechanism of action of the non-steroidal anti-inflammatory agents. This paper reports the electrophysiological effects of bradykinin and prostaglandin E1 both alone and in combination on cutaneous afferent nerve strands of the rat. MethodsThe method used by Fjallbrant & Iggo (1961) was adapted for use in rats. Male albino rats, 220-270 g, were anaesthetized with urethane (1250-1500 mg/kg i.p.). The trachea and jugular vein were cannulated and an incision was made in the skin of the right hind limb overlying the saphenous nerve. A thread was placed under the femoral artery proximal to branching of the saphenous artery and branches other than the saphenous artery were ligated. A cannula was then inserted in a retrograde direction into the femoral artery distal to branching of the saphenous artery. During insertion of the cannula slight tension was exerted on the thread under the femoral artery to prevent blood loss. The cannula was filled with Tyrode solution before insertion and connected to a three-way tap. Provided there was no leak in the cannula or tap there was no backflow of blood into the cannula and hence heparin was not used in these experiments. The dorsal surface of the right hind limb was then partially embedded in gypsum and a liquid paraffin pool was made over the saphenous nerve. Recordings were made from dissected multifibre strands of the nerve using silver wire electrodes. The signals were amplified and simultaneously displayed on an oscilloscope and recorded on magnetic tape. Drugs in volumes 0.05-0.1 ml were usually injected into the arterial cannula over a period of 30 s and followed by 0.1 ml of Tyrode solution injected over the following 30 seconds. A control injection of 0.2 ml of Tyrode solution was tested at the start of each experiment. Activity in the strands was observed for a minimum time of 10 min following an injection. I...

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

THE EFFECTS OF BRADYKININ AND PROSTAGLANDIN E₁ ON RAT CUTANEOUS AFFERENT NERVE ACTIVITY

Chahl

Iggo

1977

100

“…It has recently been reported (Crunkhorn & Willis, 1971;Freeman & West, 1972) that prostaglandins of the E series (e.g. prostaglandins El and E2) increase vascular permeability in the skin of rats whereas those of the F series (e.g.…”

Section: Introductionmentioning

confidence: 99%

Prostaglandins, Kinin and Inflammation in the Rat

Thomas¹,

West²

1974

Prostaglandin E1 and bradykinin exert synergistic effects on vascular permeability in rat skin and in rat paws. Prostaglandin E2 is inactive in this respect. Prostaglandin F2α reduces the bradykinin response in rat skin but not in rat paws. It also markedly reduces the response of the skin to dextran, 5‐hydroxytryptamine and histamine. Prostaglandin E1 and dextran exert synergistic effects in rat skin when threshold doses of each agent are used. Rats genetically resistant to dextran fail to respond to intradermal dextran in the presence of prostaglandin E1.

“…Whereas the anti-inflammatory and anti-pyretic aspects of their activity could be adequately explained by this mechanism, the analgesic action was more difficult to account for, because the available data concerning the 'algesic' activity of prostaglandins were, until very recently, contradictory. On the one hand there were reports that prostaglandins applied to the blister base (Horton, 1963) or given by intradermal injection (Crunkhorn & Willis, 1971) did not produce pain; on the other, intravenous or intramuscular injections caused pain (Karim, 1971 ; Collier, Karim, Robinson & Somers, 1972;Gillespie, 1972). Recently Collier & Schneider (1972) found that prostaglandins injected into the peritoneal cavity of mice elicited a writhing response which, in contrast to that produced by other substances like bradykinin, could not be blocked by aspirinlike drugs.…”

Section: Introductionmentioning

confidence: 99%

Prostaglandins and the mechanism of analgesia produced by aspirin‐like drugs

Ferreira

Moncada

Vane

1973

311

Summary1. Resting splenic venous outflow from anaesthetized dogs contains prostaglandin-like material: the concentration increases after intra-arterial injections of bradykinin into the spleen, and is abolished by treatment with indomethacin. 2. Intra-arterial injections of bradykinin into the spleen of lightly anaesthetized dogs elicit a dose-dependent reflex increase in the blood pressure, which is reduced but not abolished by treatment with indomethacin. 3. Addition of prostaglandin E1 or E2 either by injections or by infusions restores the reflex increase in the blood pressure due to bradykinin injections after indomethacin treatment. 4. The sensitizing action of endogenously released prostaglandins at or near the afferent nerve endings is discussed. 5. The analgesic activity of aspirin-like drugs is explained in terms of the removal of the sensitizing activity of prostaglandins.