Molecular Signatures of Maladaptive Plasticity in the Amygdala in a Rat Model of Chronic Neuropathic Pain.

Overview

1. Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA; (P.P.); (B.R.K.)
2. Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA
3. Garrison Institute on Aging, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA

Abstract

Chronic pain, a complex multidimensional disorder, remains a major healthcare issue and a therapeutic challenge. Neuropathic pain is a chronic pain condition that results from damage or dysfunction in the nervous system. While mechanisms of neuropathic pain at the peripheral and spinal cord level have been extensively studied, pain mechanisms in the brain remain underexplored. The amygdala, a limbic brain region, has emerged as a critical brain area for the emotional–affective dimension of pain and pain modulation. Amygdala neuroplasticity has been associated with pain states, but the exact molecular and cellular mechanisms underlying these states and the transition from acute to chronic pain are not well understood. Here, we used the spinal nerve ligation (SNL) model of neuropathic pain in male rats to investigate changes in gene expression in the amygdala at the chronic pain stage using RNA sequencing (RNA-Seq). Two amygdala nuclei, the basolateral (BLA) and central (CeA), were investigated in a hemisphere-dependent manner. We used an integrative approach that focuses on functional significance and cell-type specificity of differentially expressed genes (DEGs) to nominate mechanistic targets for central regulation of chronic pain. Our integrative transcriptomic and bioinformatic analyses identified individual genes (e.g., Cxcl10, Cxcl12, Mbp, Plp1, Mag, Mog, Slc17a6, Gad1, and Sst), molecular pathways (e.g., cytokine-mediated signaling pathway), biological processes (e.g., myelination, synaptic transmission), and specific cell types (e.g., oligodendrocytes, glutamatergic, and GABAergic neurons) affected by chronic pain. Our results also provide some evidence for the emerging concept of hemispheric lateralization of pain processing in the amygdala. Overall, our study proposes oligodendrocyte dysfunction in the amygdala, neuroimmune signaling in the CeA, and glutamatergic neurotransmission in the BLA as key processes and potential therapeutic targets for the management of chronic neuropathic pain.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE325961, at NCBI GEO; found in the text, “2.3. RNA Isolation and Bulk Sequencing”

Data Availability Statement

The datasets generated during and/or analyzed during the current study were uploaded to GEO with a delayed release date (GSE325961 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325961)).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 7 keywords, 11 MeSH terms, 2 funders, 60 references.

Cite

This paper

Presto, P., Cardenas, J., Bustamante, C., Kisby, B. R., Ji, G., Ponomareva, O., Neugebauer, V., & Ponomarev, I. (2026). Molecular Signatures of Maladaptive Plasticity in the Amygdala in a Rat Model of Chronic Neuropathic Pain. Cells, 15(9), 775. https://doi.org/10.3390/cells15090775

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