A Pilot Study: Comparative Effects of Green Tea Extract and Duloxetine on Oxaliplatin-Induced Allodynia in a Murine Model

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Background/Objectives: The purpose of this preclinical pilot study was to explore the potential of green tea extract (GTE) to mitigate and/or prevent oxaliplatin-induced allodynia and axonal damage in rats, when compared to duloxetine (DLX), an ASCO-recommended treatment for established neuropathic pain. Methods: Using a randomized, placebo-controlled experimental design, Sprague Dawley rats (N = 41) received 4 intraperitoneal oxaliplatin (2 mg/kg) injections every other day over 7 days. One week prior to the first oxaliplatin dose, animals began 1 of 4 interventions (saline; GTE 100 mg/kg; DLX 3 mg/kg; GTE 100 mg/kg + DLX 3 mg/kg). A naïve group (n = 6) that received no neurotoxic oxaliplatin or intervention was added to serve as a baseline measure for sNfL. Interventions were administered daily for 4 weeks. Mechanical sensitivity (allodynia) was measured 3 times per week using von Frey testing to determine paw withdrawal thresholds. Von Frey testing began one day prior to the start of interventions to establish baselines and continued through Day 35. Groups were compared to their respective baselines to calculate changes in paw withdrawal thresholds. To measure axonal damage, alterations in serum levels of neurofilament light (sNfL) protein were measured at Day 35 using ELISA. Group differences were identified using two-way analysis of variance (ANOVA). Pearson correlation coefficient was used for correlation analysis between paw withdrawal thresholds and sNfL levels at Day 35. Partial eta-squared and Hedges’ g were used to measure effect sizes. Statistical significance was assigned at P ≤ 0.05 with a 95% confidence interval. Results: Overall, the saline group showed significant reductions in mean paw withdrawal thresholds across experimental timepoints, denoting more severe allodynia caused by oxaliplatin. Conversely, intervention groups exhibited mean paw withdrawal thresholds that were significantly greater than the saline group, indicating less allodynia. The average level of sNfL was also significantly higher in the saline group (113.58 ± 43.84 pg/mL) compared to GTE100 (72.75 ± 26.85), DLX3 (59.93 ± 20.57), and DLX3 + GTE100 (77.04 ± 24.35) intervention groups, suggesting less oxaliplatin-induced axonal damage in these groups. The naïve group exhibited the lowest levels of sNfL (45.69 ± 14.64) when compared to the oxaliplatin-receiving groups (saline and intervention). There were large effect sizes between the saline group, naïve (g = 1.88), GTE100 (g = 1.123), DLX3 (g = 1.157), and DLX3 + GTE100 (g = 1.030) groups. There was also a moderate negative correlation [r(30) = −0.38, p = 0.04] between sNfL levels and paw withdrawal thresholds. Conclusions: The preliminary findings from this pilot study suggest that GTE may be an effective, nutraceutical intervention for mitigating OIPN-associated neuropathic pain, warranting further investigation as an intervention to mitigate chemotherapy-associated neurotoxicities like OIPN.

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