Peptide bam-818 Aug 2018 23:19
The Journal of neuroscience : the official journal of the Society for Neuroscience
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BAM8–22 peptide produces itch and nociceptive sensations in humans independent of histamine release
Parul Sikand, Xinzhong Dong, and Robert H. LaMotte
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Abstract
Chronic itch accompanying many dermatological, neurological and systemic diseases is unresponsive to antihistamines. Our knowledge of endogenous chemicals that evoke histamine-independent itch and their molecular targets is very limited. Recently it was demonstrated in behavioral and cellular experiments that bovine adrenal medulla 8–22 peptide (BAM8–22), a proteolytically cleaved product of proenkephalin A, is a potent activator of Mas-related G protein-coupled receptors (Mrgprs), MrgprC11 and hMrgprX1, and induces scratching in mice in a Mrgpr-dependent manner. To study the sensory qualities that BAM8–22 evokes in humans we tested the volar forearm of 15 healthy volunteers with heat-inactivated cowhage spicules previously soaked in the peptide. BAM8–22 produced itch in each subject, usually accompanied by sensations of pricking/stinging and burning. The sensations were occasionally accompanied by one or more mechanically evoked dysesthesias, namely alloknesis, hyperknesis, and hyperalgesia, but no wheal or neurogenic flare in the skin surrounding the application site. The inactive truncated peptide BAM8–18 produced weak or no sensations. Pretreatment of the tested skin with an antihistamine cream (doxepin) inhibited the histamine-induced sensations, dysesthesias and skin reactions but not the sensations and dysesthesias evoked by BAM8–22. We show that BAM8–22 produces itch and nociceptive sensations in humans in a histamine-independent manner. Thus, BAM8–22 may be an endogenous itch mediator that activates, in humans, MrgprX1, a novel target for potential anti-itch treatments.
Introduction
The most well studied itch mediator, histamine, is released from mast cells to evoke itch and nociceptive sensations. Histamine-induced itch is accompanied by the presence of a wheal reaction, due to the enhanced permeability of blood vessels, and a reddening of the skin termed a “neurogenic flare” that is produced by an axonal reflex reaction. Though antihistamines block histamine-induced itch they are typically ineffective in treating the itch accompanying many dermatological and systemic disorders such as atopic dermatitis and diseases of the liver and kidney.
The spicules of the tropical plant Mucuna pruriens, commonly known as cowhage evoke itch and lesser nociceptive sensations (LaMotte et al., 2009) in a histamine-independent manner (Johanek et al., 2007) by releasing a cysteine protease capable of activating protease-activating receptors 2 and 4 (Reddy et al., 2008). Similar itch and nociceptive sensations are evoked by spicules previously soaked i
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