Despite the fact that severe itch is a significant clinical problem, there is a relative absence of information about central neural mechanisms of itch compared to pain. It is hypothesized that itch is signaled by a population of nociceptive spinal dorsal horn neurons that respond to intracutaneous (i.c.) microinjection of pruritic chemicals. In anesthetized (or decerebrate spinalized) rats, responses of lumbar spinal neurons to i.c. microinjection of pruritic and algesic chemicals will be recorded. The following hypotheses about potential itch- signaling neurons will be tested. 1. They should respond to i.c. pruritic chemicals (histamine, serotonin) in a dose-related manner that parallels human itch sensation, and that is blocked by H1 receptor antagonists or depletion of cutaneous mast cell granulocytes (using compound 48/80). 2. Since mildly painful scratching relieves itch, mechanical (rub, scratch) or noxious thermal stimuli are predicted to either inhibit (:selectivity~ hypothesis), or to sum with (~occlusion~ hypothesis), neuronal responses evoked by pruritogens. 3. The size of the neuron~s mechanical receptive field is predicted to expand following i.c. histamine in parallel with the ~alloknesis~ (itchy skin) that develops in a larger area around the site of histamine application in humans. 4. Itch-signaling neurons should project in the spinothalamic (pain and temperature) tract. The sensitivity of antidromically identifies spinothalamic tract neurons to i.c. pruritogens will be tested. 5. Because itch may be under supraspinal modulatory (e.g., volitional) influences, responses of itch-signaling neurons are predicted to be suppressed, and possibly also facilitated, by stimulation at different sites in the brain stem. 6. Because opiate analgesics normally do not relieve itch and may even induce it, responses of spinal neurons to i.c. histamine are predicted to be enhanced by systemic administration of morphine in a naloxone- reversible manner. Additional experiments will analyze the time course, alteration of dose-response curve, and spinal vs. Supraspinal sites of morphine effects. 7. Because pretreatment of the skin with capsaicin reduces subsequent chemogenic itch and pain, we will test if i.c. capsaicin excites neurons, and reduces subsequent responses to histamine, capsaicin, and other chemicals. 8. While the primary aim is to identify characteristics that might distinguish itch-from pain-signaling neurons, a secondary aim is to establish the extent to which spinal nociceptive neurons respond non- selectively to a variety of irritant chemicals as possible mediators of a ~common chemical sense~. Responses of individual neurons to a wide spectrum of pruritic and algesic chemicals will be tested.
Showing the most recent 10 out of 14 publications
