ORIGINAL RESEARCH article
Front. Pain Res.
Sec. Neuropathic Pain
Volume 6 - 2025 | doi: 10.3389/fpain.2025.1602036
Bidirectional Modulation of Somatostatin-expressing Interneurons in the Basolateral Amygdala Reduces Neuropathic Pain Perception in Mice
Provisionally accepted
- Columbia University, New York City, United States
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Neuropathic pain is characterized by mechanical allodynia and thermal (heat and cold) hypersensitivity, yet the underlying neural mechanisms remain poorly understood. This study examines the role of inhibitory interneurons in the basolateral amygdala (BLA) in modulating pain perception following nerve injury. Chemogenetic 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. These 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.
Keywords: basolateral amygdala, neuropathic pain, Somatostatin, parvalbumin, Chemogenetic manipulation, Von Frey test, Hargreaves test, Acetone test
Received: 28 Mar 2025; Accepted: 24 Jul 2025.
Copyright: © 2025 Apte, Fernald, Slater, Sorrentino, Youngerman and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qi Wang, Columbia University, New York City, United States
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