Highlights d Periostin induces itch behavior in mice, dogs, and nonhuman primates d Periostin directly activates sensory neurons through its integrin a V b3 receptor d TSLP induces the secretion of periostin in keratinocytes via the JAK/STAT pathway d A TSLP-periostin mutual activation loop might be involved in chronic allergic itch

Fig. 1. (A) Double in situ hybridization (ISH) reveals that the neuropeptide natriuretic polypeptide b (NPPB) (green) co-expresses interleukin (IL)-31receptor (red). (B) Double ISH of IL-31Ra co-expresses oncostatin M receptor (OSMR). (C) Itch responses to subcutaneously injected IL-31 (1.5 nmol) were significantly attenuated in NPPB knockout mice and mice treated with NPPB-saporin. (D) No differences in itch responses were observed in mice lacking B-and T-cell receptors (NOD/SCID) compare to control mice (NOD). Itch behaviors were observed in mice within 30 min of administering IL-31. Each column represents the mean ± SEM, n ≥ 6 mice for each group, **p < 0.01.

Somatosensation encompasses a wide range of sensations including pain, itch, touch, and temperature and is essential for the detection of environmental stimuli, ultimately allowing an organism to escape, communicate, and adapt to its environment. Such sensations are detected by primary sensory neurons whose nerve endings are located in the skin. Compared to external stimuli, mechanisms underlying endogenous stimulation of primary sensory neurons, such as by lipids, are still largely unknown. Here, we focus on one of the endogenous bioactive lipids, sphingosine-1-phosphate (S1P), to investigate the physiological roles of S1P in pain and itch. We showed that S1P-induced calcium responses in sensory neurons through S1P receptors. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) are nonselective calcium-permeable ion channels that are known to be involved in pain and itch. Neurons that respond to S1P show reduced responsiveness when treated with antagonists that block either TRPA1 or TRPV1 alone or in combination. In addition, using single and double knockout mice (TRPA1; TRPV1; TRPA1/TRPV1) with loss of function of these channels, we demonstrated that both TRP channels are involved in S1P-induced neuronal responses in vitro. Next, we examined the effects of S1P on pain and itch responsiveness in freely behaving mice post-S1P injection into the cheek, neck, and hind paw. Our findings reveal that S1P induces both pain and itch in vivo and that these responses are partially dependent upon the TRPV1, but not TRPA1 channels.

BackgroundWe recently demonstrated that brain natriuretic peptide is expressed in the dorsal root ganglia, and that brain natriuretic peptide is required for normal detection of pruritogens. We further showed that the receptor for brain natriuretic peptide, natriuretic peptide receptor A, is present in the spinal cord, and elimination of these neurons profoundly attenuates scratching to itch-inducing compounds. However, the potential modulatory roles of brain natriuretic peptide in nociception, inflammation, and neuropathic mechanisms underlying the sensation of pain have not been investigated in detail.FindingsTo demonstrate the involvement of brain natriuretic peptide in pain, we compared the behavioral responses of brain natriuretic peptide knockout mice with their wild-type littermates. First, we showed that brain natriuretic peptide is not required in chemically induced pain responses evoked by the administration of capsaicin, allyl isothiocyanate, adenosine 5′-triphosphate, or inflammatory soup. We further measured pain behaviors and found no involvement of brain natriuretic peptide in hot, cold, or mechanical nociceptive responses in mice, nor did we find evidence for the involvement of brain natriuretic peptide in neuroinflammatory sensitization elicited by complete Freund’s adjuvant or in neuropathic pain.ConclusionsThese results demonstrate that brain natriuretic peptide is not essential for pain-related behaviors.

Highlights d Periostin induces itch behavior in mice, dogs, and nonhuman primates d Periostin directly activates sensory neurons through its integrin a V b3 receptor d TSLP induces the secretion of periostin in keratinocytes via the JAK/STAT pathway d A TSLP-periostin mutual activation loop might be involved in chronic allergic itch