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“Itchy Skin,” and Tickle Sensations

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“Itchy Skin,” and Tickle Sensations NEURAL MECHANISMS INVOLVED IN ITCH, “ITCHY SKIN,” AND TICKLE SENSATIONS David T. Graham, … , Helen Goodell, Harold G. Wolff J Clin Invest. 1951;30(1):37-49. https://doi.org/10.1172/JCI102414. Research Article Find the latest version: https://jci.me/102414/pdf NEURAL MECHANISMS INVOLVED IN ITCH, "ITCHY SKIN," AND TICKLE SENSATIONS By DAVID T. GRAHAM, HELEN GOODELL, AND HAROLD G. WOLFF (From the New York Hospital and the Departments of Medicine [Neurology] and Psychiatry, Cornell University Medical College, New York City) (Submitted for publication August 4, 1950; accepted, October 10, 1950) Available evidence suggests that the sensa- nate further the neural mechanisms involved in tion of itching is closely related to that of pain itch, "itchy skin" and tickle sensation. (1). Titchener (2) observed that when the skin was explored with a fine hair, well-defined points ITCH were found which gave rise to itching when the in- Subjects and methods tensity of stimulation was low, and to pain on The subjects were healthy adults, chiefly the authors, stronger stimulation. Bishop (3) found that itch- although other individuals participated from time to time. ing resulted from repetitive low intensity electrical Itching was elicited by the application of cowhage to an stimulation of pain spots in the skin. Lewis, Grant area of sldn approximately 1 cm. in diameter. Cowhage and Marvin (4) pointed out that noxious stimuli, is the familiar "itch powder," consisting of the fine fibers or spicules of the plant Mucuna pruriens. It was found if their intensity be decreased, can be made to by trial that the itch so produced was indistinguishable produce itching instead of pain. Forster (5) and from that following the bites of mosquitoes, or the intra- Bickford (6) reported that in patients who had cutaneous injection of histamine. When an area of sldn undergone section of the lateral spinothalamic on the arm, hand, leg or back was used for experimental procedures the corresponding areas on the opposite side tracts, thus abolishing perception of cutaneous of the body served as control. pain but not of touch, itch was also abolished. Bickford also observed this combination of sensory Description of sensation induced following ap- changes in two patients with syringomyelia. plication of cowhage to the skin Ehrenwald and K6nigstein (7), however, stated that they had found two cases of syringomyelia Cowhage applied to an area of skin approxi- with loss of pain but preservation of touch and itch, mately 1 cm. in diameter induced, usually within and one in which pain was intact but touch and 10-20 seconds, an intense itching sensation which itch absent. McMurray (8) and Kunkle and had both burning and pricking qualities. It was Chapman (9) found that individuals who were localized but seemed to spread for a few millimeters constitutionally insensitive to pain were likewise beyond the borders of the stimulated area. These insensitive to itching, but they experienced touch itch sensations sometimes merged into pain of a sensation. Bickford observed that itching and burning and pricking quality. The skin under the pain disappeared at the same time when a cu- cowhage rapidly became red, and a flare sometimes taneous nerve was anesthetized. Hardy, Wolff spread into adjacent areas of skin. When the and Goodell (10) observed that in addition to feel- area involved was the volar surface of the forearm, ings of warmth, occasional itching resulted from the flare spread as far as 2 cm. proximally and sustained thermal irradiation at an intensity not distally and approximately % to 1 cm. laterally. quite strong enough to induce pain. Th6le (11) Within a few minutes after application of the found during spinal anaesthesia, as the sensitivity cowhage, the skin several centimeters proximally of the skin to painful stimuli decreased, that stimuli and distally around the itching area became hypo- which initially induced pain later induced itching algesic to pin prick, and around the edge of this and finally no sensation at all. zone was a narrow band of hyperalgesia to pin In the present investigation many of the ex- prick, approximately % cm. wide. The itching periments described by Goldscheider (12), Bick- from cowhage spontaneously diminished after a ford, and Lewis and associates have been repeated. few minutes and did not return until the cowhage Additional experiments were designed to illumi- was mechanically agitated; or until it was re- 37 38 DAVID T. GRAHAM, HELEN GOODELL, AND HAROLD G. WOLFF vived by stroking the surrounding skin with the Experiment 2. Demonstration of itching sensation with finger tip or a blunt object. a burning quality When the cowhage applied to the skin produced a) In a series of six experiments on four subjects an intense itching, the sensation sometimes eventu- ischemia of the forearm was obtained by a pressure of 200 mm. Hg maintained around the upper arm by means ally became indistinguishable from pain. Further- of a sphygmomanometer cuff. After about 20 minutes of more, occasionally cowhage on normal skin and ischemia in the arm, a pin prick applied to the fingers in areas of primary or secondary hyperalgesia in- and the hand elicited pain of long latency which was duced pain alone. Also, as mentioned above, a poorly localized, and burning in character. The "first" heat stimulus at an intensity just below that suffi- pain was absent, as was light touch. Within these areas of altered sensibility the applica- cient to elicit pain, elicited itching. tion of cowhage on a site approximately 1 cm. in diameter on the back of the hand resulted in itching which was Peripheral Fiber Pathways Involved in Itch different from that obtained in Experiment 1, in that it Sensation was diffuse and poorly localized, seemed to be a little It has been demonstrated that stimulation of distance beneath the surface of the skin, and was "burn- human skin with a pin may give rise to two ing" in quality. the However, in more proximal areas of the ischemic fore- kinds of painful sensation. The first pain to be arm, closer to the occluding cuff, where normal pain and perceived after the application of the pin is de- touch sensation were retained, cowhage produced itching scribed as "pricking" and is punctate, superficial no different from that in skin of the opposite arm with and well localized. This has been referred to as blood and nerve supply intact. b) The course of a branch of a superficial cutaneous "first" or "fast" pain. There is also a second, dif- nerve in the forearm was mapped through a distance of ferent type of pain, described as "burning," which 4-6 cm. by means of faradic stimulation in two subjects. is perceived as more diffuse and less superficial A soft lead tubing was applied over the nerve and held in than the "pricking" pain. Since this "burning" place by tapes. Brine at a temperature of -2° to - 4° C pain is perceived after a slightly but definitely was circulated through it for 30 minutes, resulting in the progressive anesthetization of the area supplied by the longer latent period than the "pricking" pain, it nerve (16). has been referred to as "second" or "slow" pain After 30 minutes, within this area of altered sensation (13, 14). Although Lewis denied that these ex- "second" pain could be elicited by a pin point but "first" periences constituted different qualities of cutane- pain and light touch were absent. In these areas "burn- ous pain, others have recognized the qualitative ing" itch could be elicited by cowhage but not "pricking" difference. Most individuals can readily distin- itch. guish between the "pricking" and "burning" in Comment cutaneous pain (15), especially if they are sepa- It was thus possible to separate the usual itch rately presented by the experimental methods de- sensation, as it occurs after insect bites or the ap- scribed below. plication of cowhage, into two components. These The work of both Lewis and co-workers and corresponded in quality to the two types of cutane- Gasser and co-workers suggests that the "fast" ous pain, and the results of differential blocking of pain is a function of myelinated fibers, the "slow" cutaneous nerves indicate that they are mediated pain of unmyelinated ones (14). by different fibers. It is suggested that "pricking" Experiment 1. Demonstration of an itching sensation itch is carried by the myelinated fibers responsible wvith pricking quality for "first" pain, and that "burning" itch is carried In three subjects procaine hydrochloride 1% was in- by unmyelinated fibers responsible for the "second" filtrated about a cutaneous nerve on the ventral aspect pain. Since either kind of itch could occur in skin of the forearm. Within a few minutes there developed in which touch perception was absent, it seems distal to the site of infiltration an area in which pin nerves are not prick elicited only a sharp, superficial, well-localized pain probable that touch receptors and of short latency-the "first" pain. The slower, diffuse involved in the perception of itchirig. and burning "second" pain was not felt. It might be objected that the sensory changes Within this area of altered sensibility cowhage elicited following obstruction of the circulation are due to itching which was sharp, pricking, superficial, and readily interference of fluid movement which might modify In areas localized. There was no burning component. rather than to where there was complete absence of pain sensitivity, but the function of sensory end organs, where light touch was still present, itching was not felt. any functional change in the nerves themselves. NEURAL MECHANISMS IN ITCH, ITCHY SKIN, AND TICKLE 39 Against this assumption is the evidence that nor- mal sensation was retained in skin close to the oc- cluding cuff, but still distal to the obstruction, where fluid movement was as much interfered with as in the more distal areas where sensory changes did occur.
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