Neuroscience and Pain Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India.
Neuroscience and Pain Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India.
Int Immunopharmacol. 2023 Dec;125(Pt A):111100. doi: 10.1016/j.intimp.2023.111100. Epub 2023 Oct 27.
Chemotherapy-induced neuropathic pain (CINP) is one of the most prominent and incapacitating complication associated with chemotherapeutic regimens. The exact mechanisms underlying CINP are not fully understood yet, which hampers the development of effective therapeutics. The current study has been designed to investigate the effect of bergenin on CINP and dissect the underlying cellular and molecular mechanisms. Behavioural responsiveness assays were conducted in rats before and after CINP induction and at different time points post-bergenin treatment. We also measured alterations in tight junction proteins, pro-inflammatory cytokines, microglia activity, transient receptor potential (TRP) channels (TRPV1, TRPA1 and TRPM8) and N-methyl-D-aspartate receptor subtype 2 (NR2B) in dorsal root ganglion (DRG) and spinal tissues of neuropathic rats. Bergenin treatment leads to a significant and dose-dependent reduction in evoked and spontaneous ongoing pain without causing central side effects in neuropathic rats. Furthermore, treatment with bergenin and gabapentin did not affect the baseline pain threshold in healthy, non-chemotherapy-treated rats, as evaluated through tail-flick and tail-clip assays. Chemotherapy administration leads to a significant activation of TRP channels, concurrent with microglial activation, disruption of spinal cord tight junction proteins, and subsequent infiltration of pro-inflammatory cytokines, as well as NR2B activation. Notably, bergenin treatment effectively reversed all of these alterations, with the exception of TRPM8, in both the DRG and spinal cord of neuropathic rats. Findings from the present study suggests that bergenin mitigates neuropathic pain by modulating the TRPA1/TRPV1/NR2B signalling and presents a promising therapeutic avenue for the treatment of chemotherapy-induced neuropathic pain.
化疗诱导的神经性疼痛（CINP）是与化疗方案相关的最显著和使人丧失能力的并发症之一。CINP 的确切机制尚未完全了解，这阻碍了有效治疗方法的发展。本研究旨在研究贝加因对 CINP 的影响，并剖析其潜在的细胞和分子机制。在 CINP 诱导前后以及贝加因治疗后不同时间点，在大鼠中进行行为反应性测定。我们还测量了神经病理性大鼠背根神经节（DRG）和脊髓组织中紧密连接蛋白、促炎细胞因子、小胶质细胞活性、瞬时受体电位（TRP）通道（TRPV1、TRPA1 和 TRPM8）和 N-甲基-D-天冬氨酸受体 2 型（NR2B）的变化。贝加因治疗导致神经性大鼠的诱发性和自发性持续性疼痛显著且剂量依赖性降低，而无中枢副作用。此外，贝加因和加巴喷丁治疗并未通过尾巴闪烁和尾巴夹试验评估对健康、未经化疗治疗的大鼠的基础疼痛阈值产生影响。化疗给药导致 TRP 通道显著激活，同时小胶质细胞激活、脊髓紧密连接蛋白破坏以及随后促炎细胞因子和 NR2B 激活。值得注意的是，贝加因治疗有效逆转了神经性大鼠 DRG 和脊髓中所有这些改变，除了 TRPM8。本研究的结果表明，贝加因通过调节 TRPA1/TRPV1/NR2B 信号来减轻神经性疼痛，并为治疗化疗诱导的神经性疼痛提供了有前途的治疗途径。
