Background & Aims

The lateral habenula?LHb?is a microstructure located posteromedially to the dorsal thalamus. As a key neuroanatomical hub, it plays a crucial role in modulating various physiological and behavioral processes, including stress, anxiety, sleep, and reward. The LHb primarily consists of glutamatergic neurons with diverse functions depending on the stimuli encountered. However, the precise involvement of the LHb in mediating peripheral nociceptive stimulation remains unknown.

Methods

Male C57BL/6J mice (6-10 weeks of age, 20-30g) were utilized. Nociceptive stimuli were induced using plantar formalin or paraformaldehyde injection, ice (0 ?)?hot water (53 ?), tail pinch, and spared nerve injury (SNI). Immunohistochemistry was employed to investigate the expression of the c-Fos protein in the LHb. The activity of LHb neurons was measured using a fiber photometry system and in-vitro electrophysiology recordings. Chemogenetic manipulation was used to modulate nociceptive stimulation mediated by specific neurons within the LHb.

Results

Formalin and SNI test induced significantly stronger nociceptive behaviors. We identified a distinct group of LHb neurons, primarily concentrated in the rostral region, showed significantly higher proportion of c-Fos signals under nociceptive stimulation compared with their controls. Nociceptive stimulation, achieved through mechanical stimulation with a 2 g von Frey filament and tail pinch?significantly enhanced calcium signaling in glutamatergic neurons of the LHb. Moreover, the neuronal firing frequency in the rostral LHb was notably elevated in mice with SNI-induced neuropathic pain at one week after surgery compared to sham controls. Furthermore, selective activation of glutamatergic neurons in the rostral LHb of naive mice using chemogenetic manipulation induced hyperalgesia, whereas inhibiting the activity of these neurons alleviated pain in SNI mice.

Conclusions

Our findings shed light on the involvement of glutamatergic neurons located in the rostral region of the LHb in modulating peripheral nociceptive stimulation. Manipulation of these neurons by chemogenetic technology demonstrates their potential for regulating pain behavior. These findings suggest the presence of a distinct population of “pain” neurons in the rostral LHb, thereby contributing to the understanding of the complexity of brain sensory processing and its alteration in chronic neuropathic pain.
Acknowledgement: This study was supported by the National Natural Science Foundation of China?32060186?to TL and the Innovation Foundation of Jiangxi Province?YC2023-B060?to HCS

References

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Presenting Author

Huichao Sun

Poster Authors

TAO LIU

PhD

The First Affiliated Hospital of Nanchang University

Lead Author

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Huichao Sun

master

the First Affiliated Hospital, Jiangxi Medical Hospital, Nanchang University

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Qiyuan Wang

the First Affiliated Hospital, Jiangxi Medical Hospital, Nanchang University

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Junying Bao

bachelor

Lead Author

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Mengye Zhu

Lead Author

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Daying Zhang

The First Affiliated Hospital of Nanchang University

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Topics

  • Mechanisms: Biological-Systems (Physiology/Anatomy)