Department of Pathology

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Browsing Department of Pathology by browse.metadata.advisor "Chetty, Sean"

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    An investigation on the role of oxytocin in chronic neuropathic pain in a Wistar Rat Model
    (Stellenbosch : Stellenbosch University, 2023-03) de Kock, Michaela; Qulu, Lihle; Chetty, Sean; Ahmed Sherif, Isa; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Division of Medical Physiology.
    ENGLISH ABSTRACT: Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect with ineffective preventative and curative treatment, due to the condition's complexity perpetuated by the extensive central involvement, including the chronic disruption and subsequent dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Currently, only Duloxetine has been recommended as effective treatment for CIPN, which has shown individual-dependent, short-term analgesic effects, with limiting adverse effects and poor bioavailability. The neuropeptide, oxytocin, may offer significant analgesic and anxiolytic potential, as it exerts central and peripheral attenuating effects on nociception. However, it is unknown whether the intervention administered in a model of CIPN is an effective therapeutic alternative. Materials and Methods The intervention was divided into two phases. Phase 1 aimed to induce CIPN in adult Wistar rats using the chemotherapeutic agent Paclitaxel. Mechanical (electronic von Frey filament) and thermal (acetone evaporation test and Hargreaves test) hypersensitivity testing was used to evaluate changes due to the neuropathic induction. Phase 2 consisted of a 14-day intervention period with saline (o.g.), Duloextine (o.g.), or oxytocin (i.n.) administered as treatment. Analgesic behavioural testing was assessed throughout the intervention period. Following the intervention, anxiety-like behaviour was assessed using the elevated plus maze (EPM) and light-dark box protocols. Analysis of peripheral plasma corticosterone, peripheral plasma oxytocin, and hypothalamic oxytocin concentrations were assessed using ELISA assays. Results The findings showed that we were able to successfully establish a model of chemotherapy-induced peripheral neuropathy during Phase 1, determined by the increase in mechanical and thermal nociceptive responses following chemotherapy administration. Furthermore, based on this finding, we were able to evaluate the effect of different treatments administered in the presence of CIPN. The animals treated with oxytocin displayed a significant improvement in mechanical sensitivity over the intervention phase, indicative of an improvement in nociceptive tolerance in the presence of neuropathic pain. Animals that received Paclitaxel and treated with oxytocin also displayed significantly greater explorative behaviour during the EPM, indicative of a reduced presence of anxiety-like behavior. Conclusion Our results support the hypothesis that intranasally administered oxytocin may augment the analgesic and anxiolytic effects of duloxetine in a chemotherapy-induced peripheral neuropathy model in a Wistar rat. Administered in conjunction, oxytocin and duloxetine may provide enhanced therapeutic effects in the treatment of CIPN. Further research is necessary to establish optimal treatment and dosage requirements.