| Itching (pruritus) is a clinical problem that can become difficult to manage, and is associated with dermatitis, renal/liver disease, and opiate administration. However, there is little known about neural mechanisms and pathways that subserve itch sensation, and it is unclear whether itch and pain share common pathways, or if each is conveyed separately. Immunohistochemical (c-fos), electrophysiological, and behavioral methods were used to test the hypothesis that itch is conveyed by “itch-specific” spinal neurons that selectively respond to pruritogens, without responding to algesic stimuli. In all experiments, 1–10μl intracutaneous (ic) injections of pruritic or algesic chemicals were delivered to either the plantar hindpaw or the rostral back of male Sprague-Dawley rats. Regardless of the type of stimulus (chemical, thermal, mechanical) delivered to the hindpaw, similar distributions of fos-like immunoreactivity were localized mainly to superficial laminae (I and II) of the dorsal horn. Extracellularly-recorded single dorsal horn units were isolated using a novel histamine search stimulus to identify potential chemospecific neurons. Nearly all neurons responded to noxious thermal, mechanical, and a variety of chemical stimuli. Two mechanically-insensitive units responded to ic chemicals and weakly to noxious heat. Histamine-evoked responses in superficial neurons were significantly longer than in deep neurons. Whereas histamine and heat-evoked responses in superficial neurons were either facilitated or depressed by low-dose intrathecal morphine, responses in deep neurons were uniformly depressed. While histamine and capsaicin failed to elicit hindlimb scratching, is 5-HT and formalin caused significant scratching. Although histamine does not appear to be pruritic in rats, 21/24 histamine-responsive superficial dorsal horn neurons also responded to 5-HT in a manner that matched the pattern and duration of scratching behavior. The present results suggest that polymodal nociceptive superficial dorsal horn neurons are capable of signaling itch as well as pain. A smaller proportion of chemospecific and/or mechanically-insensitive neurons may also participate in signaling itch and chemogenic pain. Background, theories, interpretation of results, and development of animal models concerning itch and its relation to pain are discussed. A new model is proposed to describe the properties of spinal itch and pain pathways and their interactions. |
