2018.04.27

ACC to dorsal medial striatum inputs modulate histaminergic itch sensation

Abstract

Itch is an unpleasant sensation that initiates scratching behavior. Itch-scratch reaction is a complex phenomenon whose occurrence implicates supraspinal structures required for regulation of sensory, emotional, cognitive, and motivational aspects. However, the central mechanisms underlying the processing of itch and the interplay of the supraspinal regions and spinal cord in regulating itch-scratch processes are poorly understood. Here, we have identified that the neural projections from anterior cingulate cortex (ACC) to dorsal medial striatum (DMS) constitute a critical circuit element for regulating itch-related behaviors in the brain of male C57BL/6J mice. Moreover, we demonstrate that ACC-DMS projections selectively modulate histaminergic, but not nonhistaminergic itch-related behavior. And photoactivation of ACC-DMS projections has also no significant effects on pain behavior induced by thermal, mechanical and chemical stimuli except for a relief on inflammatory pain evoked by formalin and Complete Freund’s adjuvant (CFA). We further demonstrate that the dorsal spinal cord exerts an inhibitory effect on itch signal from ACC-DMS projections through B5-I neurons, which represent a population of spinal inhibitory interneurons that mediate the inhibition of itch. Thus, this study has presented the first evidence that the ACC-DMS projections modulate histaminergic itch-related behavior and revealed an interplay between the supraspinal and spinal levels in histaminergic itch regulation.

180427.full

2018.04.13

By Babina Sanjel

TRPV1 gain-of-function mutation impairs pain and itch sensations in mice.

Duo L^1,^2,³, Hu L^1,^2,³, Tian N⁴, Cheng G⁴, Wang H^1,^2,³, Lin Z¹, Wang Y⁴, Yang Y^1,^2,³

Abstract

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel, which can detect various noxious stimuli that cause pain, inflammation, hyperalgesia, and itch. TRPV1 knock-out mice show deficiency in nociception, but the in vivo effects of persistent activation of TRPV1 are not completely understood. Here, we generated TRPV1 knock-in mice with a G564S mutation. In the heterologous expression system, an electrophysiological study showed that the G564S mutation in mouse TRPV1 caused increased basal current and a leftward shift of voltage dependence. Intriguingly, using behavioral analysis, we found that knock-in mice showed a thermosensory defect, impaired inflammatory thermal pain, and capsaicin sensitivity. We also demonstrated an attenuated behavioral response to the pruritic agent histamine in the knock-in mice. Indeed, calcium imaging together with electrophysiology showed that the overactive mutant had decreased capsaicin sensitivity. Western blot analysis revealed that the G564S mutant reduced TRPV1 phosphorylation and cell membrane trafficking. Together, we have generated a mouse model with a gain-of-function mutation in Trpv1 gene and demonstrated that the pain and histamine-dependent itch sensations in these mice are impaired due to a decreased phosphorylation level and reduced membrane localization of TRPV1.

KEYWORDS:

Transient receptor potential vanilloid 1; gain of function; itch; pain; phosphorylation; trafficking

TRPV1 gain-of-function mutation impairs pain and itch sensation in mice.

18.04.06

By qhsl93

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

Abstract

Itch is often triggered by warming the skin in patients with itchy dermatitis, but the underlying mechanism is largely unknown. We presently investigated if warming the skin enhances histamine- or serotonin (5-HT)-evoked itch behavior or responses of sensory dorsal root ganglion (DRG) cells, and if responses of superficial dorsal horn neurons to innocuous warming are enhanced by these pruritogens. In a temperature-controlled environmental chamber, mice exhibited greater scratching following intradermal injection of 5-HT, but not histamine, SLIGRL, or BAM8-22, when the skin surface temperature was above 36°C. Calcium imaging of DRG cells in a temperature-controlled bath revealed that responses to 5-HT, but not histamine, were significantly greater at a bath temperature of 35°C vs. lower temperatures. Single-unit recordings revealed a subpopulation of superficial dorsal horn neurons responsive to intradermal injection of 5-HT. Of these, 58% responded to innocuous skin warming (37°C) prior to intradermal injection of 5-HT, while 100% responded to warming following intradermal injection of 5-HT. Warming-evoked responses were superimposed on the 5-HT-evoked elevation in firing and were significantly larger compared with responses pre-5-HT, as long as 30 min after the intradermal injection of 5-HT. Five-HT-insensitive units, and units that either did or did not respond to intradermal histamine, did not exhibit any increase in the incidence of warmth sensitivity or in the mean response to warming following intradermal injection of the pruritogen. The results suggest that 5-HT-evoked responses of pruriceptors are enhanced during skin warming, leading to increased firing of 5-HT-sensitive dorsal horn neurons that signal nonhistaminergic itch.

akiyama2016