Effectiveness of Duloxetine on Oxaliplatin-induced Allodynia and Hyperalgesia in Rats.

Biological research for nursing Pub Date : 2024-04-01 Epub Date: 2023-10-30 DOI:10.1177/10998004231209444
Monica A Wagner, Ellen M Lavoie Smith, Naji Ayyash, Josue Toledo, Zainab Rasheed, Janean E Holden
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Abstract

Development of painful oxaliplatin-induced peripheral neuropathy (OIPN) is a major problem in people who receive oxaliplatin as part of cancer treatment. The pain experienced by those with OIPN can be seriously debilitating and lead to discontinuation of an otherwise successful treatment. Duloxetine is currently the only recommended treatment for established painful OIPN recommended by the American Society of Clinical Oncology, but its preventative ability is still not clear. This study examined the ability of duloxetine to prevent signs of chronic OIPN in female (n = 12) and male (n = 21) rats treated with the chemotherapeutic agent oxaliplatin. Using an established model of OIPN, rats were started on duloxetine (15 mg) one week prior to oxaliplatin administration and continued duloxetine for 32 days. Behavioral testing for mechanical allodynia and mechanical hyperalgesia was done with selected von Frey filaments. Significant posttreatment differences were found for allodynia in female (p = .004), but not male rats. Duloxetine was associated with significant differences for hyperalgesia in both female (p < .001) and male (p < .001) rats. These findings provide preliminary evidence of the preventative effects of duloxetine on both oxaliplatin-induced allodynia and hyperalgesia in male and female rats, with a difference noted in response between the sexes.

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度洛西汀对奥沙利铂诱导的大鼠异常疼痛和痛觉过敏的疗效。
在接受奥沙利铂作为癌症治疗的患者中,疼痛的奥沙利铂诱导的周围神经病变(OIPN)的发展是一个主要问题。OIPN患者所经历的疼痛可能会使人严重衰弱,并导致其他成功治疗的中断。度洛西汀是目前美国临床肿瘤学会推荐的唯一一种治疗疼痛性OIPN的推荐药物,但其预防能力尚不清楚。本研究检测了度洛西汀在接受化疗药物奥沙利铂治疗的雌性(n=12)和雄性(n=21)大鼠中预防慢性OIPN症状的能力。使用已建立的OIPN模型,大鼠在奥沙利铂给药前一周开始服用度洛西汀(15mg),并持续服用度洛西汀32天。用选定的von Frey细丝进行机械性异常性疼痛和机械性痛觉过敏的行为测试。治疗后发现雌性大鼠的异常性疼痛有显著差异(p=0.004),但雄性大鼠没有。在雌性(p<.001)和雄性(p<0.001)大鼠中,度洛西汀与痛觉过敏的显著差异相关。这些发现为度洛西汀对奥沙利铂诱导的雄性和雌性大鼠的异常性疼痛和痛觉过敏的预防作用提供了初步证据,性别之间的反应存在差异。
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