Hmgb1 Silencing in the Amygdala Inhibits Pain-Related Behaviors in a Rat Model of Neuropathic Pain
Chronic pain presents a therapeutic challenge due to the highly complex interplay of sensory, emotional-affective and cognitive factors. The mechanisms of the transition from acute to chronic pain are not well understood. We hypothesized that neuroimmune mechanisms in the amygdala, a brain region in...
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/15/11944 |
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| author | Peyton Presto Guangchen Ji Olga Ponomareva Igor Ponomarev Volker Neugebauer |
| author_facet | Peyton Presto Guangchen Ji Olga Ponomareva Igor Ponomarev Volker Neugebauer |
| author_sort | Peyton Presto |
| collection | DOAJ |
| description | Chronic pain presents a therapeutic challenge due to the highly complex interplay of sensory, emotional-affective and cognitive factors. The mechanisms of the transition from acute to chronic pain are not well understood. We hypothesized that neuroimmune mechanisms in the amygdala, a brain region involved in the emotional-affective component of pain and pain modulation, play an important role through high motility group box 1 (Hmgb1), a pro-inflammatory molecule that has been linked to neuroimmune signaling in spinal nociception. Transcriptomic analysis revealed an upregulation of Hmgb1 mRNA in the right but not left central nucleus of the amygdala (CeA) at the chronic stage of a spinal nerve ligation (SNL) rat model of neuropathic pain. Hmgb1 silencing with a stereotaxic injection of siRNA for Hmgb1 into the right CeA of adult male and female rats 1 week after (post-treatment), but not 2 weeks before (pre-treatment) SNL induction decreased mechanical hypersensitivity and emotional-affective responses, but not anxiety-like behaviors, measured 4 weeks after SNL. Immunohistochemical data suggest that neurons are a major source of Hmgb1 in the CeA. Therefore, Hmgb1 in the amygdala may contribute to the transition from acute to chronic neuropathic pain, and the inhibition of Hmgb1 at a subacute time point can mitigate neuropathic pain. |
| first_indexed | 2024-03-11T00:26:08Z |
| format | Article |
| id | doaj.art-2a5c100a172d4452b6061fc598a85c0d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:26:08Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2a5c100a172d4452b6061fc598a85c0d2023-11-18T22:58:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124151194410.3390/ijms241511944Hmgb1 Silencing in the Amygdala Inhibits Pain-Related Behaviors in a Rat Model of Neuropathic PainPeyton Presto0Guangchen Ji1Olga Ponomareva2Igor Ponomarev3Volker Neugebauer4Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USAChronic pain presents a therapeutic challenge due to the highly complex interplay of sensory, emotional-affective and cognitive factors. The mechanisms of the transition from acute to chronic pain are not well understood. We hypothesized that neuroimmune mechanisms in the amygdala, a brain region involved in the emotional-affective component of pain and pain modulation, play an important role through high motility group box 1 (Hmgb1), a pro-inflammatory molecule that has been linked to neuroimmune signaling in spinal nociception. Transcriptomic analysis revealed an upregulation of Hmgb1 mRNA in the right but not left central nucleus of the amygdala (CeA) at the chronic stage of a spinal nerve ligation (SNL) rat model of neuropathic pain. Hmgb1 silencing with a stereotaxic injection of siRNA for Hmgb1 into the right CeA of adult male and female rats 1 week after (post-treatment), but not 2 weeks before (pre-treatment) SNL induction decreased mechanical hypersensitivity and emotional-affective responses, but not anxiety-like behaviors, measured 4 weeks after SNL. Immunohistochemical data suggest that neurons are a major source of Hmgb1 in the CeA. Therefore, Hmgb1 in the amygdala may contribute to the transition from acute to chronic neuropathic pain, and the inhibition of Hmgb1 at a subacute time point can mitigate neuropathic pain.https://www.mdpi.com/1422-0067/24/15/11944amygdalaneuropathic painHmgb1neuroimmune signalingbehavior |
| spellingShingle | Peyton Presto Guangchen Ji Olga Ponomareva Igor Ponomarev Volker Neugebauer Hmgb1 Silencing in the Amygdala Inhibits Pain-Related Behaviors in a Rat Model of Neuropathic Pain International Journal of Molecular Sciences amygdala neuropathic pain Hmgb1 neuroimmune signaling behavior |
| title | Hmgb1 Silencing in the Amygdala Inhibits Pain-Related Behaviors in a Rat Model of Neuropathic Pain |
| title_full | Hmgb1 Silencing in the Amygdala Inhibits Pain-Related Behaviors in a Rat Model of Neuropathic Pain |
| title_fullStr | Hmgb1 Silencing in the Amygdala Inhibits Pain-Related Behaviors in a Rat Model of Neuropathic Pain |
| title_full_unstemmed | Hmgb1 Silencing in the Amygdala Inhibits Pain-Related Behaviors in a Rat Model of Neuropathic Pain |
| title_short | Hmgb1 Silencing in the Amygdala Inhibits Pain-Related Behaviors in a Rat Model of Neuropathic Pain |
| title_sort | hmgb1 silencing in the amygdala inhibits pain related behaviors in a rat model of neuropathic pain |
| topic | amygdala neuropathic pain Hmgb1 neuroimmune signaling behavior |
| url | https://www.mdpi.com/1422-0067/24/15/11944 |
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