Systemic and Peripheral Mechanisms of Cortical Stimulation-Induced Analgesia and Refractoriness in a Rat Model of Neuropathic Pain
Epidural motor cortex stimulation (MCS) is an effective treatment for refractory neuropathic pain; however, some individuals are unresponsive. In this study, we correlated the effectiveness of MCS and refractoriness with the expression of cytokines, neurotrophins, and nociceptive mediators in the do...
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| author | Danielle V. Assis Ana Carolina P. Campos Amanda F. N. Paschoa Talita F. Santos Erich T. Fonoff Rosana L. Pagano |
| author_facet | Danielle V. Assis Ana Carolina P. Campos Amanda F. N. Paschoa Talita F. Santos Erich T. Fonoff Rosana L. Pagano |
| author_sort | Danielle V. Assis |
| collection | DOAJ |
| description | Epidural motor cortex stimulation (MCS) is an effective treatment for refractory neuropathic pain; however, some individuals are unresponsive. In this study, we correlated the effectiveness of MCS and refractoriness with the expression of cytokines, neurotrophins, and nociceptive mediators in the dorsal root ganglion (DRG), sciatic nerve, and plasma of rats with sciatic neuropathy. MCS inhibited hyperalgesia and allodynia in two-thirds of the animals (responsive group), and one-third did not respond (refractory group). Chronic constriction injury (CCI) increased IL-1β in the nerve and DRG, inhibited IL-4, IL-10, and IL-17A in the nerve, decreased β-endorphin, and enhanced substance P in the plasma, compared to the control. Responsive animals showed decreased NGF and increased IL-6 in the nerve, accompanied by restoration of local IL-10 and IL-17A and systemic β-endorphin. Refractory animals showed increased TNF-α and decreased IFNγ in the nerve, along with decreased TNF-α and IL-17A in the DRG, maintaining low levels of systemic β-endorphin. Our findings suggest that the effectiveness of MCS depends on local control of inflammatory and neurotrophic changes, accompanied by recovery of the opioidergic system observed in neuropathic conditions. So, understanding the refractoriness to MCS may guide an improvement in the efficacy of the technique, thus benefiting patients with persistent neuropathic pain. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:18:27Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c7ea73f3942d434a8005f6b22b4b6a7e2023-11-17T23:00:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01249779610.3390/ijms24097796Systemic and Peripheral Mechanisms of Cortical Stimulation-Induced Analgesia and Refractoriness in a Rat Model of Neuropathic PainDanielle V. Assis0Ana Carolina P. Campos1Amanda F. N. Paschoa2Talita F. Santos3Erich T. Fonoff4Rosana L. Pagano5Laboratory of Neuroscience, Hospital Sírio-Libanês, São Paulo 01308-060, SP, BrazilLaboratory of Neuroscience, Hospital Sírio-Libanês, São Paulo 01308-060, SP, BrazilLaboratory of Neuroscience, Hospital Sírio-Libanês, São Paulo 01308-060, SP, BrazilLaboratory of Neuroscience, Hospital Sírio-Libanês, São Paulo 01308-060, SP, BrazilDivision of Functional Neurosurgery, Department of Neurology, University of Sao Paulo Medical School, São Paulo 05402-000, SP, BrazilLaboratory of Neuroscience, Hospital Sírio-Libanês, São Paulo 01308-060, SP, BrazilEpidural motor cortex stimulation (MCS) is an effective treatment for refractory neuropathic pain; however, some individuals are unresponsive. In this study, we correlated the effectiveness of MCS and refractoriness with the expression of cytokines, neurotrophins, and nociceptive mediators in the dorsal root ganglion (DRG), sciatic nerve, and plasma of rats with sciatic neuropathy. MCS inhibited hyperalgesia and allodynia in two-thirds of the animals (responsive group), and one-third did not respond (refractory group). Chronic constriction injury (CCI) increased IL-1β in the nerve and DRG, inhibited IL-4, IL-10, and IL-17A in the nerve, decreased β-endorphin, and enhanced substance P in the plasma, compared to the control. Responsive animals showed decreased NGF and increased IL-6 in the nerve, accompanied by restoration of local IL-10 and IL-17A and systemic β-endorphin. Refractory animals showed increased TNF-α and decreased IFNγ in the nerve, along with decreased TNF-α and IL-17A in the DRG, maintaining low levels of systemic β-endorphin. Our findings suggest that the effectiveness of MCS depends on local control of inflammatory and neurotrophic changes, accompanied by recovery of the opioidergic system observed in neuropathic conditions. So, understanding the refractoriness to MCS may guide an improvement in the efficacy of the technique, thus benefiting patients with persistent neuropathic pain.https://www.mdpi.com/1422-0067/24/9/7796motor cortex stimulationneuropathic painsciatic nerveinflammationneurotrophinssubstance P |
| spellingShingle | Danielle V. Assis Ana Carolina P. Campos Amanda F. N. Paschoa Talita F. Santos Erich T. Fonoff Rosana L. Pagano Systemic and Peripheral Mechanisms of Cortical Stimulation-Induced Analgesia and Refractoriness in a Rat Model of Neuropathic Pain International Journal of Molecular Sciences motor cortex stimulation neuropathic pain sciatic nerve inflammation neurotrophins substance P |
| title | Systemic and Peripheral Mechanisms of Cortical Stimulation-Induced Analgesia and Refractoriness in a Rat Model of Neuropathic Pain |
| title_full | Systemic and Peripheral Mechanisms of Cortical Stimulation-Induced Analgesia and Refractoriness in a Rat Model of Neuropathic Pain |
| title_fullStr | Systemic and Peripheral Mechanisms of Cortical Stimulation-Induced Analgesia and Refractoriness in a Rat Model of Neuropathic Pain |
| title_full_unstemmed | Systemic and Peripheral Mechanisms of Cortical Stimulation-Induced Analgesia and Refractoriness in a Rat Model of Neuropathic Pain |
| title_short | Systemic and Peripheral Mechanisms of Cortical Stimulation-Induced Analgesia and Refractoriness in a Rat Model of Neuropathic Pain |
| title_sort | systemic and peripheral mechanisms of cortical stimulation induced analgesia and refractoriness in a rat model of neuropathic pain |
| topic | motor cortex stimulation neuropathic pain sciatic nerve inflammation neurotrophins substance P |
| url | https://www.mdpi.com/1422-0067/24/9/7796 |
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