Pain‐producing substance in human inflammatory exudates and plasma

Abstract

We have previously reported the occurrence of a pain-producing agent in the fluid removed from a cantharidin blister (Armstrong, Dry, Keele & Markham, 1953). In the present paper we shall show that fluids from other kinds of blister, and human inflammatory exudates such as the joint fluid in rheumatoid arthritis, pleural effusion and hydrocoele fluid can also cause pain. The presence of the pain-producing substance is due to the mode of collection, and it is possible to obtain these fluids in an inactive state by preventing contact with glass. In 1953 we reported that plasma did not produce pain but it will be shown here that plasma does in fact develop labile pain-producing activity when collected and kept in a glass syringe. When blood or an inflammatory exudate is collected into a siliconed syringe and transferred to polythene vessels very little activity develops within one hour.With regard to the nature of the pain-producing substance, we had originally thought that the substance in blister fluid might be 5-hydroxytryptamine (5-HT). However, further work on both pain production and on the responses of the isolated rat uterus shows that the active agent is not 5-HT, but that it is probably a polypeptide resembling bradykinin in its actions.The findings here presented were the subject of short communications by Armstrong, Hobbiger, Jepson & Keele (1953); Argent, Armstrong, Jepson, Keele & Phillips (1954); Armstrong, Keele, Jepson & Stewart (1954); Armstrong, Jepson, Keele & Stewart (1955);and Jepson, Armstrong, Keele & Stewart (1956). METHODS Pain-producing activity of inflammatory exudates was estimated by the method described in detail by Armstrong, Dry et al. (1953). The exudates (about 0-2 ml.) were applied to the exposed base of a cantharidin blister and a subjective estimate of pain was recorded on a moving smoked drum.Uterus-stimulating activity of inflammatory exudates was measured on the isolated rat uterus.The uterus was suspended in an isolated organ bath of 5 or 30 ml. capacity. The bath fluid had the

Potentiation of the Algogenic Action of Bradykinin by an Inhibitor of Angiotensin I Converting Enzyme, Captopr1l (Sq 14,225)

“…The present results also suggest that SQ 14,225 may potentiate pathological pain in acute inflammation since the involvement of kinins (including bradykinin) has been suggested (15), and if so augmentation of the algogenic action by SQ 14,225 would be less in the somatic area than in the visceral area. Alternatively, if SQ 14,225 fails in this regard, the involve ment of kinins in pathological pain in acute inflammation should be ruled out.…”

Tobacco/nicotine and endogenous brain opioids

“…These, presumably local analgesic effects were apparently due to nicotine. Armstrong et al (1957), Keele (1962), Keele and Armstrong (1964) used exposed sensory nerve endings in the base of a cantharidin blister on the forearm skin of human volunteers. They studied the pain response to locally applied acetylcholine and nicotine.…”

The Clearance of Neurohypophysial Hormones From the Circulation of Non‐mammalian Vertebrates

“…Blood was withdrawn from the cannulated artery of anaesthetized and heparinized chickens and toads. The blood was collected in polythene centrifuge tubes surrounded by ice and care was taken to avoid contact with glass to avoid the formation of kinins (Armstrong, Jepson, Keele & Stewart, 1957). The blood was centrifuged at 35,500 rev/min for 30 min at 50 C, the plasma removed with a plastic syringe into a chilled polythene centrifuge tube; 10 volumes of acetone were then added, mixed quickly, and allowed to stand for 10 min to complete the flocculation of the proteins.…”