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
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