Bidirectional modulation of somatostatin-expressing interneurons in the basolateral amygdala reduces neuropathic pain perception in mice.

Abstract

<h4>Introduction</h4>Neuropathic pain is characterized by mechanical allodynia and thermal (heat and cold) hypersensitivity, yet the underlying neural mechanisms remain poorly understood.<h4>Methods</h4>Using chemogenetic excitation and inhibition, we examined the role of inhibitory interneurons in the basolateral amygdala (BLA) in modulating pain perception following nerve injury.<h4>Results</h4>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.<h4>Discussion</h4>Our 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.