Innocuous warming enhances peripheral serotonergic itch signaling and evokes enhanced responses in serotonin-responsive dorsal horn neurons in the mouse

Abstract

Skin warming often exacerbates itch in patients with itchy dermatitis. We demonstrate that warming the skin enhanced serotonin-evoked, but not histamine-evoked, itch behavior and responses of sensory dorsal root ganglion cells. Moreover, serotonin, but not histamine, enhanced responses of superficial dorsal horn neurons to innocuous warming. The results suggest that skin warming selectively enhances the responses of serotonin-sensitive pruriceptors, leading to increased firing of serotonin-sensitive dorsal horn neurons that signal nonhistaminergic itch.

Alloknesis and hyperknesis—mechanisms, assessment methodology, and clinical implications of itch sensitization

“…The particular modality-switch dysesthesia in which itch is evoked in by algogens 63 or exclusively painful stimuli, is not includable in current definitions of alloknesis and hyperknesis (See Table 1). It has been observed in patients with AD, in healthy subjects with evoked contact dermatitis and in mice models 5,38,102 and is not associated with any specific term. In this review the term algoknesis will be applied to describe this sensory phenomenon, which conceivably rely on mechanisms distinct from those of hyperknesis and alloknesis.…”

“…In rodents, innocuous warming aggravates serotonergic but not histaminergic itch 5 . AD patients consistently report that their itch is worsened by warmth 10,51,142 .…”

Nonhistaminergic and mechanical itch sensitization in atopic dermatitis

“…The most frequent emotional descriptors were: "annoying" = 4 (3.25-4), "bothersome" = 4 (3-4), and "my only desire: no itch" = 4 (3-4). Significant sleep interference from itch was reported = 3 (3)(4). The mean Itch Severity Scale score was 12.5 ± 0.4 (0-21 scale), and the average SCORAD was 35.4 ± 3.1 (0-103 scale).…”

“…The itch characteristics, presented as medians and quartiles on a Likert Scale 0-4, were most consistently described as: "warm" = 3 (3-4), "burning" = 3, (3-4), "searing" = 3 (2-4), and "stinging" = 3 (1. . The most prevalent perceived aggravating factor was "warmth" (3,(3)(4), and "cold" was most consistently described as alleviatory = 3 (3)(4). The most frequent emotional descriptors were: "annoying" = 4 (3.25-4), "bothersome" = 4 (3-4), and "my only desire: no itch" = 4 (3-4).…”

“…Mean perfusion assessment as well as area quantification techniques could not be reliably applied because of significant ceiling effects (presumably both physiological and technological) observed in the lesional skin of the AD patients ( Fig. 5, column a-b, row [4][5][6]. No group differences were found in relation to wheal sizes when comparing lesional or non-lesional areas.…”