Background & Aims
The majority of neuropathic pain patients, i.e., peripheral or central pain, are hypersensitive to various stimuli including innocuous cold or mechanical stimuli. While role of peripheral nociceptors for cold hyperalgesia is relatively understood well, the underlying mechanism of cold hyperalgesia in the patients with central pain syndrome has been under-explored.Parabrachial nucleus (LPBN) is critical for both autonomic and behavioral thermoregulatory responses and lateral hypothalamus (LH) is also known to regulate thermoregulatory behavior. Thus, we investigated the role of LPBN-LH pathway in generation of cold hyperalgesia in mice.
Methods
Optogenetic method, Fiber photometry, 2D-electrophoresis, Acetone evaporation test?Immunofluroresience.
Results
Optogenetic stimulation of e LPBN-LH projections for 10 min using blue laser evoked cold hyperalgesia within 10 min after stimulation, lasting up to at least 2 months, which was reversed by optogenetic inhibition of LPBN-LH pathway. Our fiber photometry study showed the LH-projecting LH neurons were excited by cold stimuli.
Conclusions
Our findings suggest the role of LPBN-LH pathway as a the central neurocircuitry in the generation of cold hyperalgesia.
References
1. Fakhoury, M., Salman, I., Najjar, W., Merhej, G., & Lawand, N. (2020). The Lateral Hypothalamus: An Uncharted Territory for Processing Peripheral Neurogenic Inflammation. Front Neurosci, 14, 101. doi:10.3389/fnins.2020.00101
2.Jung, S., Lee, M., Kim, D. Y., Son, C., Ahn, B. H., Heo, G., . . . Kim, S. Y. (2022). A forebrain neural substrate for behavioral thermoregulation. Neuron, 110(2), 266-279 e269. doi:10.1016/j.neuron.2021.09.039
3.Yang, W. Z., Xie, H., Du, X., Zhou, Q., Xiao, Y., Zhao, Z., . . . Shen, W. L. (2023). A parabrachial-hypothalamic parallel circuit governs cold defense in mice. Nat Commun, 14(1), 4924. doi:10.1038/s41467-023-40504-6
Presenting Author
Juping Xing
Poster Authors
Topics
- Models: Chronic Pain - Neuropathic