Bidirectional modulation of somatostatin-expressing interneurons in the basolateral amygdala reduces neuropathic pain perception in mice
IntroductionNeuropathic pain is characterized by mechanical allodynia and thermal (heat and cold) hypersensitivity, yet the underlying neural mechanisms remain poorly understood.MethodsUsing chemogenetic excitation and inhibition, we examined the role of inhibitory interneurons in the basolateral am...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Pain Research |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpain.2025.1602036/full |
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| author | Aditya Apte Julia Fernald Cody Slater Cody Slater Marc Sorrentino Brett Youngerman Qi Wang Qi Wang |
| author_facet | Aditya Apte Julia Fernald Cody Slater Cody Slater Marc Sorrentino Brett Youngerman Qi Wang Qi Wang |
| author_sort | Aditya Apte |
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| description | IntroductionNeuropathic pain is characterized by mechanical allodynia and thermal (heat and cold) hypersensitivity, yet the underlying neural mechanisms remain poorly understood.MethodsUsing chemogenetic excitation and inhibition, we examined the role of inhibitory interneurons in the basolateral amygdala (BLA) in modulating pain perception following nerve injury.ResultsChemogenetic excitation of parvalbumin-positive (PV+) interneurons significantly alleviated mechanical allodynia but had minimal effects on thermal hypersensitivity. However, inhibition of PV+ interneurons did not produce significant changes in pain sensitivity, suggesting that reductions in perisomatic inhibition do not contribute to chronic pain states. In contrast, bidirectional modulation of somatostatin-positive (SST+) interneurons influenced pain perception in a modality-specific manner. Both excitation and inhibition of SST+ interneurons alleviated mechanical allodynia, indicating a potential compensatory role in nociceptive processing. Additionally, SST+ neuron excitation reduced cold hypersensitivity without affecting heat hypersensitivity, whereas inhibition improved heat hypersensitivity but not cold responses.DiscussionOur findings suggest that, in addition to PV+ neurons, SST+ interneurons in the BLA play complex roles in modulating neuropathic pain following nerve injury and may serve as a potential target for future neuromodulation interventions in chronic pain management. |
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| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pain Research |
| spelling | doaj-art-23f7a2002b4849edb9849e986e9a1f662025-08-20T03:05:31ZengFrontiers Media S.A.Frontiers in Pain Research2673-561X2025-08-01610.3389/fpain.2025.16020361602036Bidirectional modulation of somatostatin-expressing interneurons in the basolateral amygdala reduces neuropathic pain perception in miceAditya Apte0Julia Fernald1Cody Slater2Cody Slater3Marc Sorrentino4Brett Youngerman5Qi Wang6Qi Wang7Department of Biomedical Engineering, School of Engineering and Applied Science, Columbia University, New York, NY, United StatesDepartment of Biomedical Engineering, School of Engineering and Applied Science, Columbia University, New York, NY, United StatesDepartment of Biomedical Engineering, School of Engineering and Applied Science, Columbia University, New York, NY, United StatesVagelos College of Physicians and Surgeons, Columbia University, New York, NY, United StatesDepartment of Biomedical Engineering, School of Engineering and Applied Science, Columbia University, New York, NY, United StatesDepartment of Neurosurgery, Columbia University Irving Medical Center, Columbia University, New York, NY, United StatesDepartment of Biomedical Engineering, School of Engineering and Applied Science, Columbia University, New York, NY, United StatesDepartment of Neurosurgery, Columbia University Irving Medical Center, Columbia University, New York, NY, United StatesIntroductionNeuropathic pain is characterized by mechanical allodynia and thermal (heat and cold) hypersensitivity, yet the underlying neural mechanisms remain poorly understood.MethodsUsing chemogenetic excitation and inhibition, we examined the role of inhibitory interneurons in the basolateral amygdala (BLA) in modulating pain perception following nerve injury.ResultsChemogenetic excitation of parvalbumin-positive (PV+) interneurons significantly alleviated mechanical allodynia but had minimal effects on thermal hypersensitivity. However, inhibition of PV+ interneurons did not produce significant changes in pain sensitivity, suggesting that reductions in perisomatic inhibition do not contribute to chronic pain states. In contrast, bidirectional modulation of somatostatin-positive (SST+) interneurons influenced pain perception in a modality-specific manner. Both excitation and inhibition of SST+ interneurons alleviated mechanical allodynia, indicating a potential compensatory role in nociceptive processing. Additionally, SST+ neuron excitation reduced cold hypersensitivity without affecting heat hypersensitivity, whereas inhibition improved heat hypersensitivity but not cold responses.DiscussionOur findings suggest that, in addition to PV+ neurons, SST+ interneurons in the BLA play complex roles in modulating neuropathic pain following nerve injury and may serve as a potential target for future neuromodulation interventions in chronic pain management.https://www.frontiersin.org/articles/10.3389/fpain.2025.1602036/fullbasolateral amygdalaneuropathic painsomatostatinparvalbuminchemogenetic manipulationvon Frey test |
| spellingShingle | Aditya Apte Julia Fernald Cody Slater Cody Slater Marc Sorrentino Brett Youngerman Qi Wang Qi Wang Bidirectional modulation of somatostatin-expressing interneurons in the basolateral amygdala reduces neuropathic pain perception in mice Frontiers in Pain Research basolateral amygdala neuropathic pain somatostatin parvalbumin chemogenetic manipulation von Frey test |
| title | Bidirectional modulation of somatostatin-expressing interneurons in the basolateral amygdala reduces neuropathic pain perception in mice |
| title_full | Bidirectional modulation of somatostatin-expressing interneurons in the basolateral amygdala reduces neuropathic pain perception in mice |
| title_fullStr | Bidirectional modulation of somatostatin-expressing interneurons in the basolateral amygdala reduces neuropathic pain perception in mice |
| title_full_unstemmed | Bidirectional modulation of somatostatin-expressing interneurons in the basolateral amygdala reduces neuropathic pain perception in mice |
| title_short | Bidirectional modulation of somatostatin-expressing interneurons in the basolateral amygdala reduces neuropathic pain perception in mice |
| title_sort | bidirectional modulation of somatostatin expressing interneurons in the basolateral amygdala reduces neuropathic pain perception in mice |
| topic | basolateral amygdala neuropathic pain somatostatin parvalbumin chemogenetic manipulation von Frey test |
| url | https://www.frontiersin.org/articles/10.3389/fpain.2025.1602036/full |
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