Janean E Holden
The University of Michigan, USA
Title: Pretreatment with duloxetine may prevent chemotherapy-induced neuropathic pain: A pilot study
Biography
Biography: Janean E Holden
Abstract
Statement of the Problem: Approximately 70% of patients receiving oxaliplatin for colorectal cancer develop painful oxaliplatin- induced peripheral neuropathy (OIPN-P). OIPN-P can persist up to 11 years after treatment is stopped, affecting quality of life, and contributing to falls, depression, and sleep loss. OIPN-P also necessitates decreased dosage during treatment, thereby decreasing treatment effectiveness and increasing mortality risk. The serotonin and norepinephrine reuptake inhibitor, duloxetine, is approved for treating OIPN-P, but is effective only in about 50% of patients. Recent work is suggestive that pretreating with tricyclic drugs can prevent onset of OIPN-P, but these drugs have serious side effects. We investigated whether pretreatment with duloxetine would prevent onset of OIPN-P in male and female rats in a model of oxaliplatin-induced hyperalgesia. Methodology: Rats were pretreated with duloxetine (15 mg; PO) for 7 days prior to and through oxaliplatin treatment, and for 20 days post oxaliplatin treatment. Rats were then tested for 6 days after all treatment stopped. The measure used was a 15 g von Frey filament applied to the left foot, which measures hyperalgesia, a sign of neuropathic pain. Findings: We found that rats pretreated with duloxetine presented with significantly less hyperalgesia through the testing period compared to control, and notably for the six days after all treatment stopped (p ≤ 0.003; p ≤ 0.13; males and females resp.). Conclusion and Significance: These pilot study findings are suggestive of the need for further study to determine whether pretreatment with duloxetine can prevent onset of OIPN-P.
Recent Publications:
1.Holden JE, Wagner, MA & Reeves, B. (2018). Anatomical Evidence for Lateral Hypothalamic Innervation of the Pontine A7 Catecholamine Cell Group in Rat. Neuroscience Letters. 668:80- 85.
2.Wagner MA, Jeong Y, Banerjee T, Yang J, & Holden JE (2016). Sex differences in hypothalamic-mediated tonic norepinephrine release for thermal hyperalgesia in rats. Neuroscience, 324:420-9.
3.Wardach J, Wagner M, Jeong Y, & Holden JE (2016). Lateral hypothalamic stimulation reduces thermal hyperalgesia through spinally descending orexin-A neurons in neuropathic pain. Western Journal of Nursing Research 38:292-307.
4.Holden JE, Wang E, Moes JR, Wagner M, Maduko A, & Jeong Y (2014). Differences in carbachol dose, pain condition and sex following lateral hypothalamic stimulation. Neuroscience, 270:226- 35.
5.Jeong Y, Moes JR, Wagner M & Holden JE (2012). The posterior hypothalamus exerts opposing effects on nociception via the A7 catecholamine cell group in rat. Neuroscience, 227:144-153.
