A septo-hypothalamic-medullary circuit directs stress-induced analgesia
Stress is a potent modulator of pain. Specifically, acute stress due to physical restraint induces stress-induced analgesia (SIA). However, where and how acute stress and pain pathways interface in the brain are poorly understood. Here, we describe how the dorsal lateral septum (dLS), a forebrain li...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-01-01
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| Online Access: | https://elifesciences.org/articles/96724 |
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| author | Devanshi Piyush Shah Pallavi Raj Sharma Rachit Agarwal Arnab Barik |
| author_facet | Devanshi Piyush Shah Pallavi Raj Sharma Rachit Agarwal Arnab Barik |
| author_sort | Devanshi Piyush Shah |
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| description | Stress is a potent modulator of pain. Specifically, acute stress due to physical restraint induces stress-induced analgesia (SIA). However, where and how acute stress and pain pathways interface in the brain are poorly understood. Here, we describe how the dorsal lateral septum (dLS), a forebrain limbic nucleus, facilitates SIA through its downstream targets in the lateral hypothalamic area (LHA) of mice. Taking advantage of transsynaptic viral-genetic, optogenetic, and chemogenetic techniques, we show that the dLS→LHA circuitry is sufficient to drive analgesia and is required for SIA. Furthermore, our results reveal that the dLS→LHA pathway is opioid-dependent and modulates pain through the pro-nociceptive neurons in the rostral ventromedial medulla (RVM). Remarkably, we found that the inhibitory dLS neurons are recruited specifically when the mice struggle to escape under restraint and, in turn, inhibit excitatory LHA neurons. As a result, the RVM neurons downstream of LHA are disengaged, thus suppressing nociception. Together, we delineate a poly-synaptic pathway that can transform escape behavior in mice under restraint to acute stress into analgesia. |
| format | Article |
| id | doaj-art-020f4a4695674a7c9e0e69f8d57d422a |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-020f4a4695674a7c9e0e69f8d57d422a2025-01-20T14:46:41ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.96724A septo-hypothalamic-medullary circuit directs stress-induced analgesiaDevanshi Piyush Shah0Pallavi Raj Sharma1https://orcid.org/0000-0003-3877-7272Rachit Agarwal2Arnab Barik3https://orcid.org/0000-0001-6850-0894Centre for Neuroscience, Indian Institute of Science, Bengaluru, IndiaDepartment of Bioengineering, Indian Institute of Science, Bengaluru, IndiaDepartment of Bioengineering, Indian Institute of Science, Bengaluru, IndiaCentre for Neuroscience, Indian Institute of Science, Bengaluru, IndiaStress is a potent modulator of pain. Specifically, acute stress due to physical restraint induces stress-induced analgesia (SIA). However, where and how acute stress and pain pathways interface in the brain are poorly understood. Here, we describe how the dorsal lateral septum (dLS), a forebrain limbic nucleus, facilitates SIA through its downstream targets in the lateral hypothalamic area (LHA) of mice. Taking advantage of transsynaptic viral-genetic, optogenetic, and chemogenetic techniques, we show that the dLS→LHA circuitry is sufficient to drive analgesia and is required for SIA. Furthermore, our results reveal that the dLS→LHA pathway is opioid-dependent and modulates pain through the pro-nociceptive neurons in the rostral ventromedial medulla (RVM). Remarkably, we found that the inhibitory dLS neurons are recruited specifically when the mice struggle to escape under restraint and, in turn, inhibit excitatory LHA neurons. As a result, the RVM neurons downstream of LHA are disengaged, thus suppressing nociception. Together, we delineate a poly-synaptic pathway that can transform escape behavior in mice under restraint to acute stress into analgesia.https://elifesciences.org/articles/96724stresschronic painanalgesiaseptum |
| spellingShingle | Devanshi Piyush Shah Pallavi Raj Sharma Rachit Agarwal Arnab Barik A septo-hypothalamic-medullary circuit directs stress-induced analgesia eLife stress chronic pain analgesia septum |
| title | A septo-hypothalamic-medullary circuit directs stress-induced analgesia |
| title_full | A septo-hypothalamic-medullary circuit directs stress-induced analgesia |
| title_fullStr | A septo-hypothalamic-medullary circuit directs stress-induced analgesia |
| title_full_unstemmed | A septo-hypothalamic-medullary circuit directs stress-induced analgesia |
| title_short | A septo-hypothalamic-medullary circuit directs stress-induced analgesia |
| title_sort | septo hypothalamic medullary circuit directs stress induced analgesia |
| topic | stress chronic pain analgesia septum |
| url | https://elifesciences.org/articles/96724 |
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