ArticleThe journal of headache and pain2025
Optogenetic inhibition of ventrolateral orbitofrontal cortex astrocytes facilitates ventrolateral periaqueductal gray glutamatergic activity to reduce hypersensitivity in infraorbital nerve injury rat model.
Article in The journal of headache and pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Advances in orofacial pain research: a bibliometric analysis.Frontiers in neurology · 2025Pooled it
- Article
- Ventrolateral orbital cortex as a functional hub in chronic pain and comorbid depression.Frontiers in neuroscience · 2026Article
- The excitatory neurotransmitter glutamate and its receptors: the culprits behind neuropathic pain?Frontiers in aging neuroscience · 2026Review
- The Efficacy of Intrathecal Platelet-Rich Plasma Administration in Alleviation of Chronic Neuropathic Pain in Rat Model.Molecular neurobiology · 2025Article
- The relationship between abnormal glucose metabolism and chronic pain.Cell & bioscience · 2025Review
- Altered aminoacid and lipid metabolism in a rat orofacial inflammation model determined by omics approach: potential role in trigeminal sensitisation.The journal of headache and pain · 2025Article
- Decoding chronic pain: the glutamate-GABA tug of war in the cerebral cortex.Frontiers in molecular neuroscience · 2025Review
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6 authors.
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Abstract
backgroundTrigeminal neuropathic pain (TNP) is a chronic condition characterized by heightened nociceptive responses and neuroinflammatory changes. While astrocytes are recognized as critical players in pain modulation, their specific role in influencing descending trigeminal pain pathways via ventrolateral orbitofrontal cortex (vlOFC) activity modulation remains underexplored. Therefore, we investigated the impact of optogenetic modulation of astrocytes in the vlOFC on pain hypersensitivity in a rat model of chronic constriction injury of the infraorbital nerve (CCI-ION).
methodAdult female Sprague Dawley rats underwent ION constriction to mimic TNP symptoms, with naive and sham animals serving as controls. AAV8-GFAP-hChR2-mCherry, AAV8-GFAP-eNpHR3.0-mCherry, or AAV8-GFAP-mCherry were delivered to the vlOFC for in vivo optogenetic manipulation. Pain behaviors were assessed using acetone, von Frey, and elevated plus maze tests, while electrophysiological recordings from the ventrolateral periaqueductal gray (vlPAG) and ventral posteromedial (VPM) thalamus were obtained.
resultsOrofacial hyperalgesia, reduced vlPAG activity, and thalamic hyperexcitability were associated with vlOFC astrocytic hyperactivity in the TNP animals. In contrast, optogenetic inhibition of vlOFC astrocytes restored vlOFC glutamatergic signaling, increased vlPAG glutamatergic neuronal activity, and reduced hyperactivity in the VPM thalamus. Behavioral assessments also revealed alleviation of hyperalgesia, allodynia, and anxiety-like behaviors during the stimulation-ON phase, alongside reduced neuroinflammatory markers, including P2 × 3 and Iba-1. However, astrocytic excitation and null virus controls did not alter TNP responses, underscoring the specificity of astrocytic inhibition.
conclusionThese findings suggest that the astrocytic subpopulation in the vlOFC and its robust influence on vlPAG glutamatergic neurons play a crucial role in restoring descending pain processing pathways, potentially contributing to the development of novel therapeutic approaches for TNP management.
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