講演情報
[課題2]Intra-Trigeminal Ganglionic rIL-10 Injection Relieves Orofacial Pain via Potent β-Endorphin Release
*Lutfi Putra Perdana1, Masamitsu Oshima1, Daisuke Ikutame1, Yoshizo Matsuka1 (1. Department of Stomatognathic Function and Occlusal Reconstruction, Graduate School of Biomedical Sciences, Tokushima University)
[Objective]
Trigeminal neuropathic pain (TNP) is a chronic pain condition resulting from damage or dysfunction of the trigeminal nerve. TNP is a challenging condition due to its spontaneous, evoked, and hypersensitive pain responses, significantly impacting patients’ quality of life1. Twenty percent of patients who were prescribed first-choice drugs for TNP, discontinued their treatment because of side effects, which the European Medicines Agency categorizes as very common. 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 evaluate the potential therapeutic mechanism of IL-10 in the trigeminal ganglia (TG) of the TNP model.
[Method]
Infraorbital nerve constriction (IONC) was performed unilaterally in Sprague-Dawley rats. Recombinant IL-10 (rIL-10), PBS, and Stat3 inhibitor (STATTIC) were administered directly into TG on the IONC side seven days post-IONC. Behavior tests were conducted to measure changes in mechanical and thermal thresholds, utilizing an electronic von Frey and a thermoception analyzer, respectively. Real-time PCR analysis was used to quantify the expression levels of pain-related signaling pathways within the TG, followed by RNAscope to localise the expression. Furthermore, double immunofluorescence staining was employed to visualize the localization of β-endorphin.
[Results and Discussion]
The pain behaviors were significantly reduced after rIL-10 injection in the TNP model, indicating its potent analgesic effect. Real-time PCR and RNAscope 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 be 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 a new understanding into novel therapeutic options targeting IL-10 in TNP through β-endorphin release.
[References]
1) Pigg M, et al. International classification of orofacial pain, 1st edition (ICOP). Cephalalgia 2020;129–221.
2) Truini A, et al. Current and innovative pharmacological options to treat typical and atypical trigeminal neuralgia. Drugs 2018;1433–1442.
3) Iwasa T, Afroz S, Inoue M et al. IL-10 and CXCL2 in trigeminal ganglia in neuropathic pain. Neuroscience letters 2019;132-138.
Trigeminal neuropathic pain (TNP) is a chronic pain condition resulting from damage or dysfunction of the trigeminal nerve. TNP is a challenging condition due to its spontaneous, evoked, and hypersensitive pain responses, significantly impacting patients’ quality of life1. Twenty percent of patients who were prescribed first-choice drugs for TNP, discontinued their treatment because of side effects, which the European Medicines Agency categorizes as very common. 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 evaluate the potential therapeutic mechanism of IL-10 in the trigeminal ganglia (TG) of the TNP model.
[Method]
Infraorbital nerve constriction (IONC) was performed unilaterally in Sprague-Dawley rats. Recombinant IL-10 (rIL-10), PBS, and Stat3 inhibitor (STATTIC) were administered directly into TG on the IONC side seven days post-IONC. Behavior tests were conducted to measure changes in mechanical and thermal thresholds, utilizing an electronic von Frey and a thermoception analyzer, respectively. Real-time PCR analysis was used to quantify the expression levels of pain-related signaling pathways within the TG, followed by RNAscope to localise the expression. Furthermore, double immunofluorescence staining was employed to visualize the localization of β-endorphin.
[Results and Discussion]
The pain behaviors were significantly reduced after rIL-10 injection in the TNP model, indicating its potent analgesic effect. Real-time PCR and RNAscope 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 be 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 a new understanding into novel therapeutic options targeting IL-10 in TNP through β-endorphin release.
[References]
1) Pigg M, et al. International classification of orofacial pain, 1st edition (ICOP). Cephalalgia 2020;129–221.
2) Truini A, et al. Current and innovative pharmacological options to treat typical and atypical trigeminal neuralgia. Drugs 2018;1433–1442.
3) Iwasa T, Afroz S, Inoue M et al. IL-10 and CXCL2 in trigeminal ganglia in neuropathic pain. Neuroscience letters 2019;132-138.
