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Available evidence suggests that the sensation of itching is closely related to that of pain (1). Titchener (2) observed that when the skin was explored with a fine hair, well-defined points were found which gave rise to itching when the intensity of stimulation was low, and to pain on stronger stimulation. Bishop (3) found that itching resulted from repetitive low intensity electrical stimulation of pain spots in the skin. Lewis, Grant and Marvin (4) pointed out that noxious stimuli, if their intensity be decreased, can be made to produce itching instead of pain. Forster (5) and Bickford (6) reported that in patients who had undergone section of the lateral spinothalamic tracts, thus abolishing perception of cutaneous pain but not of touch, itch was also abolished. Bickford also observed this combination of sensory changes in two patients with syringomyelia. Ehrenwald and K6nigstein (7), however, stated that they had found two cases of syringomyelia with loss of pain but preservation of touch and itch, and one in which pain was intact but touch and itch absent. McMurray (8) and Kunkle and Chapman (9) found that individuals who were constitutionally insensitive to pain were likewise insensitive to itching, but they experienced touch sensation. Bickford observed that itching and pain disappeared at the same time when a cutaneous nerve was anesthetized. Hardy, Wolff and Goodell (10) observed that in addition to feelings of warmth, occasional itching resulted from sustained thermal irradiation at an intensity not quite strong enough to induce pain. Th6le (11) found during spinal anaesthesia, as the sensitivity of the skin to painful stimuli decreased, that stimuli which initially induced pain later induced itching and finally no sensation at all.In the present investigation many of the experiments described by Goldscheider (12), Bickford, and Lewis and associates have been repeated. Additional experiments were designed to illumi-37 nate further the neural mechanisms involved in itch, "itchy skin" and tickle sensation. ITCH Subjects and methodsThe subjects were healthy adults, chiefly the authors, although other individuals participated from time to time. Itching was elicited by the application of cowhage to an area of sldn approximately 1 cm. in diameter. Cowhage is the familiar "itch powder," consisting of the fine fibers or spicules of the plant Mucuna pruriens. It was found by trial that the itch so produced was indistinguishable from that following the bites of mosquitoes, or the intracutaneous injection of histamine. When an area of sldn on the arm, hand, leg or back was used for experimental procedures the corresponding areas on the opposite side of the body served as control.Description of sensation induced following application of cowhage to the skin Cowhage applied to an area of skin approximately 1 cm. in diameter induced, usually within 10-20 seconds, an intense itching sensation which had both burning and pricking qualities. It was localized but seemed to spread for a few millimeters beyond the borders...

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During the painful phase of attacks of vascular headache of the migraine type there is dilatation of the large and small blood vessels of the head both intra-and extracranially, often more on one side than the other.1-3 In most attacks, however, the pain stems chiefly from the large subsurface cranial arteries and their branches. Aching pain is experienced when these vessels are distended, pulled upon, or displaced. Yet dilatation of these vessels, for instance that induced by immersion of the body in hot water, is not usually painful and does not induce other focal features of the migraine attack, i.e., edema, tenderness on pressure, and heightened vulnerability of tissue to injury. These observations led to the hypothesis that in addition to vasodilatation, a local sterile inflammation occurs. Also a substance (or substances) accumulates in the walls of the arteries and in the adjacent perivascular, areolar, and supporting tissues as well that lowers pain thresholds, increases capillary permeability, and heightens vul¬ nerability to injury.4-6 MethodThe observations of Keele and his associates7 demonstrating that the pain-producing substance in blister fluid had many of the properties of the group of vasodilator polypeptides referred to as bradykinin,8 Kallidin,9 or plasma kinnins,10 led us to assay on the isolated rat uterus specimens of subsurface tissue fluid collected during head¬ ache. The rat uterus contracts in the presence of minute amounts of these polypeptides. Preliminary analysis demonstrated that specimens collected dur¬ ing headache contracted the rat uterus.6 To char¬ acterize the active substance, the rat uterus, rat duodenum, and rat blood pressure were used for quantitative assay.Bioassay Method.\p=m-\(A) Smooth Muscle: Vir¬ gin female rats (150-200 gm.) were killed by a stunning blow on the head. The bicornuate uterus and the first 8 or 10 cm. of duodenum proximate to the pylorus were removed and placed in modi¬ fied Ringer-Locke solution. In most experiments this solution contained, per liter, 9.0 gm. NaCl, 0.42 gm. KC1, 0.02 gm. CaCla, 0.50 gm. NaHCO», 0.50 gm. dextrose, and distilled water to vol¬ ume.In some experiments the CaCU concen¬ tration was increased to 0.06 gm. per liter to increase the sensitivity of the uterus to "head¬ ache stuff." A single horn of the uterus and a segment of duodenum were then cut to suitable length, and all adherent connective tissue blood vessels and fat were carefully dissected away. After rinsing the interior of the tubular muscles with the saline solution they were tied at both ends with cotton thread. The muscles were then mounted in a single 3 cc. chamber, one end of each being secured to the bottom of the chamber and