Psychophysical measurements of itch and itchy skin ("alloknesis"mdash;itch produced by innocuous mechanical stimulation) were obtained in human volunteers following intracutaneous or subcutaneous injections of histamine or papain into the volar forearm. Histamine and papain were given in doses of 0.1, 1, or 10 μg in 10 μl of saline. The effects of the depth of injection and of skin temperature on the latency, magnitude, and duration of itch were examined. Also, dose-response functions were obtained for the area of alloknesis produced by intracutaneous injections of histamine. Finally, the neural mechanisms underlying the spread of alloknesis were investigated via local anesthesia of the skin. Intracutaneous and subcutaneous injections of histamine, but not papain, produced a sensation of itch without pain. The latency of itch was shorter after an intracutanous than after a subcutaneous injection of histamine. The mean latencies of itch produced by a 1-μg dose were 9.5 and 23.0 sec for intracutaneous and subcutaneous injections, respectively. No differences were observed in the magnitude or duration of itch. Similarly, the latency of itch was increased when the skin temperature at injection site was lowered to 15°C, whereas the magnitude and duration of itch were unaffected. Intracutaneous and subcutaneous injections of histamine produced similar areas of alloknesis. However, the magnitude and duration of alloknesis were dependent on dose. The mean maximum areas of alloknesis produced by intracutaneous injections of 0.1, 1, and 10 μg of histamine were 28.3, 47.2, and 43.8 cm2, respectively. Alloknesis was present at 2 min after injection, increased to a maximum area without 10 min, and then gradually decreased during the next 25-40 min. Once developed, the area was typically abolished when the injection site was cooled to 1-4°C. Rewarming the injection site to 38°C returned the area to its original size. Also, when histamine was injected into a small area of skin anesthetized with Xylocaine, alloknesis failed to develop until the anesthetic wore off. In addition, when histamine was injected 5 mm distal to a thin mediolateral anesthetic barrier, alloknesis did not develop on the proximal side of the barrier. These results demonstrate that histamine is effective in producing itch and alloknesis, and should be useful in correlative neurophysiological studies of the underlying mechanisms. It is suggested that both peripheral and central neural mechanisms are involved in the development of alloknesis.
Bibliographical noteFunding Information:
This work was supported by U.S. Public Health Service Grant No. NS14624 to Robert H. LaMotte and by a National Research Service Award to Donald A. Simone. We thank Karen Heller for help in preparing figures and Terry O’Connor for statistical analyses.
- Itchy skin