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Trigeminal (TG), dorsal root (DRG), and nodose/jugular (NG/JG) ganglia each possess specialized and distinct functions. We used RNA sequencing of two-cycle sorted Pirt-positive neurons to identify genes exclusively expressing in L3-L5 DRG, T10-L1 DRG, NG/JG, and TG mouse ganglion neurons. Transcription factor Phox2b and Efcab6 are specifically expressed in NG/JG while Hoxa7 is exclusively present in both T10-L1 and L3-L5 DRG neurons. Cyp2f2, Krt18, and Ptgds, along with pituitary hormone prolactin (Prl), growth hormone (Gh), and proopiomelanocortin (Pomc) encoding genes are almost exclusively in TG neurons. Immunohistochemistry confirmed selective expression of these hormones in TG neurons and dural nerves; and showed GH expression in subsets of TRPV1 + and CGRP + TG neurons. We next examined GH roles in hypersensitivity in the spinal versus trigeminal systems. Exogenous GH produced mechanical hypersensitivity when injected intrathecally, but not intraplantarly. GH-induced thermal hypersensitivity was not detected in the spinal system. GH dose-dependently generated orofacial and headache-like periorbital mechanical hypersensitivity after administration into masseter muscle and dura, respectively. Periorbital mechanical hypersensitivity was reversed by a GH receptor antagonist, pegvisomant. Overall, pituitary hormone genes are selective for TG versus other ganglia somatotypes; and GH has distinctive functional significance in the trigeminal versus spinal systems., (© 2021. The Author(s).)

Rehabilitation from alcohol addiction or abuse is hampered by withdrawal symptoms including severe headaches, which often lead to rehabilitation failure. There is no appropriate therapeutic option available for alcohol-withdrawal-induced headaches. Here, we show the role of the mast-cell-specific receptor MrgprB2 in the development of alcohol-withdrawal-induced headache. Withdrawing alcohol from alcohol-acclimated mice induces headache behaviors, including facial allodynia, facial pain expressions, and reduced movement, which are symptoms often observed in humans. Those behaviors were absent in MrgprB2-deficient mice during alcohol withdrawal. We observed in vivo spontaneous activation and hypersensitization of trigeminal ganglia (TG) neurons in alcohol-withdrawal WT mice, but not in alcohol-withdrawal MrgprB2-deficient mice. Increased mast cell degranulation by alcohol withdrawal in dura mater was dependent on the presence of MrgprB2. The results indicate that alcohol withdrawal causes headache via MrgprB2 of mast cells in dura mater, suggesting that MrgprB2 is a potential target for treating alcohol-withdrawal-related headaches. • Alcohol withdrawal causes headache behaviors, depending on the presence of MrgprB2 • Alcohol-withdrawal-induced sensitization of TG is absent in MrgprB2-lacking mice • Mast cell degranulation by MrgprB2 in dura mater induces alcohol-withdrawal headache • MrgprB2 receptor mediates the development of alcohol-withdrawal-associated headache Son et al. show that activation of the mast-cell-specific receptor MrgprB2 in the dura mater of male mice causes mast cell degranulation and sensitization of sensory neurons, resulting in headache after alcohol withdrawal. [ABSTRACT FROM AUTHOR]