45: The Effect of Combination Therapy with Gabapentinoid and Goshajinkigan in a Rat Model of CIPN

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic neuropathic pain, , , , , , , , , , Pharmacological interventions

Background and Aims: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting complication of neurotoxic anticancer drugs. CIPN dominantly presents with sensory disturbances such as pain and numbness, which markedly impair daily functioning and quality of life and often necessitate dose reduction or discontinuation of chemotherapy. Despite its clinical impact, no established therapy effectively prevents or treats CIPN. A retrospective cohort study suggested that combination therapy with a gabapentinoid (GPN) and the Japanese Kampo medicine goshajinkigan (GJG) may improve CIPN symptoms. Therefore, we investigated its therapeutic potential using a rat model of CIPN.

Methods: A CIPN rat model was generated by intraperitoneal administration of cisplatin (CDDP, 3mg/kg) on day 0, 7, 14, 21. To evaluate treatment efficacy, rats were assigned to following groups: CDDP (no treatment), CDDP+GPN, CDDP+GJG, CDDP+GPN+GJG, and control (saline). In GJG treatment groups, feed containing 3% GJG was administered orally from day -7. In GPN treatment groups, pregabalin (10mg/kg) or mirogabalin (10mg/kg) was injected intraperitoneally on day 21, 28. Mechanical allodynia was measured using von Frey filaments on day 0, 7, 14, 21, 28, and also at 1 and 2 hours after GPN administration.

Results: GJG alone didn't significantly prevent mechanical allodynia compared with untreated CDDP groups, although a transient attenuation was observed on day 7. In contrast, GPN administration on day 21, 28 significantly reduced mechanical allodynia in both CDDP+GPN and CDDP+GPN+GJG groups. Notably, on day 28, the CDDP+GPN+GJG group demonstrated earlier onset and greater magnitude of analgesic effect than the CDDP+GPN group, indicating a potentiating interaction between GPN and GJG in alleviating CIPN-associated mechanical hypersensitivity.

Conclusions: Although GJG alone did not exert a significant preventive effect on CIPN-induced mechanical allodynia, it modestly delayed symptom progression and significantly enhanced GPN-induced analgesia. These findings suggest that adjunctive GJG may potentiate GPN analgesia in CIPN. Demonstrated potentiation by GJG supports the scientific rationale for addition of Kampo medicine as an adjunct in CIPN management. Elucidating the underlying mechanisms of this interaction could advance translational strategies and facilitate rational translational development of effective combination therapies for patients suffering from CIPN.

References: Co-treatment with Gabapentinoid and Japanese Herbal Medicine Goshajinkigan for CIPN is Associated with Longer Duration and Higher Dose of Chemotherapy. Miyano K, Uezono Y, Yamaguchi T, Hashimoto W, Komoriya S. Adv Ther. 2025;42(6):2833-2852.
Preventive effect of oral goshajinkigan on chronic oxaliplatin-induced hypoesthesia in rats. Kono T, Suzuki Y, Mizuno K, Miyagi C, Omiya Y, Sekine H, Mizuhara Y, Miyano K, Kase Y, Uezono Y. Sci Rep. 2015;5:16078.
Goshajinkigan, a traditional Japanese medicine, prevents oxaliplatin-induced acute peripheral neuropathy by suppressing functional alteration of TRP channels in rat. Mizuno K, Kono T, Suzuki Y, Miyagi C, Omiya Y, Miyano K, Kase Y, Uezono Y. J Pharmacol Sci. 2014;125(1):91-8.

Presenting Author: Saeko Hamaoka
Submitting Author: Saeko Hamaoka

Senior Author: Yasuhito Uezono

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Kanako Miyano: Associate Professor - Juntendo University, Faculty of Pharmacy
• Masako Iseki: Professor - Juntendo University, Faculty of Medicine
• Yasuhito Uezono: Professor - The Jikei University, School of Medicine