[HIMAWAN-4] The potent effect of IL-10 induced β-endorphin on alleviating trigeminal neuropathic pain
[Abstract]
[Objective]
Trigeminal neuropathic pain (TNP), characterized by chronic facial pain, results from trigeminal nerve damage1. The complex neural pathways contribute to the difficulty in finding effective treatments, limited relief and having undesirable side effects1. IL-10 emerges as a promising therapeutic target for pain relief 2,3. However, its mechanism has not yet been explored in TNP. This study aims to investigate the potential therapeutic mechanism of IL-10 in the trigeminal ganglia (TG) of the TNP model.
[Method]
The TNP model was established in Sprague-Dawley rats by performing Infraorbital Nerve Constriction (IONC) unilaterally. Recombinant IL-10 (rIL-10) or PBS was administered directly into TG on the IONC side seven days post-IONC. We assessed the impact of inhibiting Stat3, an essential protein involved in critical cellular processes in inflammation, by administering the Stat3 inhibitor, STATTIC. Behavior tests were conducted utilizing an electronic von Frey and a thermoception analyzer, assessed using repeated measures ANOVA followed by Tukey-HSD. Real-time PCR was performed to quantify the expression of inflammatory markers and pain-related signalling pathways within the TG and analyzed with an independent t-test. Double immunofluorescence staining was employed to visualize the localization of β-endorphin with GS and NeuN in vivo and in vitro. Differences were analyzed using one-way ANOVA followed by Tukey-HSD.
[Results and Discussion]
rIL-10 significantly reduced pain behaviors, both mechanical and thermal thresholds in the TNP model, indicating its potent analgesic effect. Real-time PCR demonstrated significant upregulation of Pomc, a gene that produces β-endorphin. Double immunofluorescence staining revealed increased β-endorphin expression in satellite glial cells and neurons. Stat3 may involved in this mechanism due to pretreatment with STATTIC significantly inhibited the antinociceptive effect of the rIL-10 and reduced β-endorphin expression. These findings open new understanding into novel therapeutic options targeting IL-10 in TNP through β-endorphin release.
[Refferences]
1) finnerup NB, Kuner R, Jensen TS. Neuropathic Pain: From Mechanisms to Physiological reviews2021; 259–301
2) vanderwall AG, Milligan ED. Cytokines in Pain: Harnessing Endogenous Anti-inflammatory signaling for improved Pain Management. Frontiers in immunology 2019; 3009
3) iwasa T, et al. IL-10 and CXCL2 in Trigeminal Ganglia in Neuropathic Pain. Neuroscience letters 2019; 132-138
[Objective]
Trigeminal neuropathic pain (TNP), characterized by chronic facial pain, results from trigeminal nerve damage1. The complex neural pathways contribute to the difficulty in finding effective treatments, limited relief and having undesirable side effects1. IL-10 emerges as a promising therapeutic target for pain relief 2,3. However, its mechanism has not yet been explored in TNP. This study aims to investigate the potential therapeutic mechanism of IL-10 in the trigeminal ganglia (TG) of the TNP model.
[Method]
The TNP model was established in Sprague-Dawley rats by performing Infraorbital Nerve Constriction (IONC) unilaterally. Recombinant IL-10 (rIL-10) or PBS was administered directly into TG on the IONC side seven days post-IONC. We assessed the impact of inhibiting Stat3, an essential protein involved in critical cellular processes in inflammation, by administering the Stat3 inhibitor, STATTIC. Behavior tests were conducted utilizing an electronic von Frey and a thermoception analyzer, assessed using repeated measures ANOVA followed by Tukey-HSD. Real-time PCR was performed to quantify the expression of inflammatory markers and pain-related signalling pathways within the TG and analyzed with an independent t-test. Double immunofluorescence staining was employed to visualize the localization of β-endorphin with GS and NeuN in vivo and in vitro. Differences were analyzed using one-way ANOVA followed by Tukey-HSD.
[Results and Discussion]
rIL-10 significantly reduced pain behaviors, both mechanical and thermal thresholds in the TNP model, indicating its potent analgesic effect. Real-time PCR demonstrated significant upregulation of Pomc, a gene that produces β-endorphin. Double immunofluorescence staining revealed increased β-endorphin expression in satellite glial cells and neurons. Stat3 may involved in this mechanism due to pretreatment with STATTIC significantly inhibited the antinociceptive effect of the rIL-10 and reduced β-endorphin expression. These findings open new understanding into novel therapeutic options targeting IL-10 in TNP through β-endorphin release.
[Refferences]
1) finnerup NB, Kuner R, Jensen TS. Neuropathic Pain: From Mechanisms to Physiological reviews2021; 259–301
2) vanderwall AG, Milligan ED. Cytokines in Pain: Harnessing Endogenous Anti-inflammatory signaling for improved Pain Management. Frontiers in immunology 2019; 3009
3) iwasa T, et al. IL-10 and CXCL2 in Trigeminal Ganglia in Neuropathic Pain. Neuroscience letters 2019; 132-138