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The lateral habenula is critically involved in histamine-induced itch sensation.

ABSTRACT: Lateral habenula (LHb) is a brain region acting as a hub mediating aversive response against noxious, stressful stimuli. Growing evidences indicated that LHb modulates aminergic activities to induce avoidance behavior against nociceptive stimuli. Given overlapped neural circuitry transmitting pain and itch information, it is likely that LHb have a role in processing itch information. Here, we examined whether LHb is involved in itchy response induced by histamine. We found that histamine injection enhances Fos (+) cells in posterior portion within parvocellular and central subnuclei of the medial division (LHbM) of the LHb. Moreover, chemogenetic suppression of LHbM reduced scratching behavior induced by histamine injection. These results suggest that LHb is required for processing itch information to induce histaminergic itchy response.

SUBMITTER: Ko HG

PROVIDER: S-EPMC7457247 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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The lateral habenula is critically involved in histamine-induced itch sensation.

Ko Hyoung-Gon HG

Molecular brain 20200827 1

Lateral habenula (LHb) is a brain region acting as a hub mediating aversive response against noxious, stressful stimuli. Growing evidences indicated that LHb modulates aminergic activities to induce avoidance behavior against nociceptive stimuli. Given overlapped neural circuitry transmitting pain and itch information, it is likely that LHb have a role in processing itch information. Here, we examined whether LHb is involved in itchy response induced by histamine. We found that histamine injecti ...[more]

PMID: 32854744

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Project description:Itch can be induced by activation of small-diameter DRG neurons, which express abundant intracellular fibroblast growth factor 13 (FGF13). Although FGF13 is revealed to be essential for heat nociception, its role in mediating itch remains to be investigated. Here, we reported that loss of FGF13 in mouse DRG neurons impaired the histamine-induced scratching behavior. Calcium imaging showed that the percentage of histamine-responsive DRG neurons was largely decreased in FGF13-deficient mice; and consistently, electrophysiological recording exhibited that histamine failed to evoke action potential firing in most DRG neurons from these mice. Given that the reduced histamine-evoked neuronal response was caused by knockdown of FGF13 but not by FGF13A deficiency, FGF13B was supposed to mediate this process. Furthermore, overexpression of histamine Type 1 receptor H1R, but not H2R, H3R, nor H4R, increased the percentage of histamine-responsive DRG neurons, and the scratching behavior in FGF13-deficient mice was highly reduced by selective activation of H1R, suggesting that H1R is mainly required for FGF13-mediated neuronal response and scratching behavior induced by histamine. However, overexpression of H1R failed to rescue the histamine-evoked neuronal response in FGF13-deficient mice. Histamine enhanced the FGF13 interaction with NaV1.7. Disruption of this interaction by a membrane-permeable competitive peptide, GST-Flag-NaV1.7CT-TAT, reduced the percentage of histamine-responsive DRG neurons, and impaired the histamine-induced scratching, indicating that the FGF13/NaV1.7 interaction is a key molecular determinant in the histamine-induced itch sensation. Therefore, our study reveals a novel role of FGF13 in mediating itch sensation via the interaction of NaV1.7 in the peripheral nervous system.SIGNIFICANCE STATEMENT Scratching induced by itch brings serious tissue damage in chronic itchy diseases, and targeting itch-sensing molecules is crucial for its therapeutic intervention. Here, we reveal that FGF13 is required for the neuronal excitation and scratching behavior induced by histamine. We further provide the evidence that the histamine-evoked neuronal response is mainly mediated by histamine Type 1 receptor H1R, and is largely attenuated in FGF13-deficent mice. Importantly, we identify that histamine enhances the FGF13/NaV1.7 interaction, and disruption of this interaction reduces histamine-evoked neuronal excitation and highly impairs histamine-induced scratching behavior. Additionally, we also find that FGF13 is involved in 5-hydroxytryptamine-induced scratching behavior and hapten 1-fluoro-2,4-dinitrobenzene-induced chronic itch.

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The lateral habenula is critically involved in histamine-induced itch sensation.

Publications

The lateral habenula is critically involved in histamine-induced itch sensation.

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