Multimodal topical gel combining 2-hydroxyflavanone, gabapentin, and ketamine alleviates diabetic vulvodynia and allodynia with concurrent tissue regeneration in streptozocin-induced rat models

Abstract

Neuropathic pain arises from damage or illness affecting either central or peripheral or both somatosensory systems. Vulvodynia, a chronic neuropathic pain disorder in women, remains largely neglected despite its significant impact. This study was aimed to evaluate safety and efficacy of a multimodal analgesic gel (MMG-10 %) in relieving diabetic neuropathic pain; specifically vulvodynia and allodynia in female rats. We have formulated a highly promising flavonoid, 2’-Hydroxyflavanone (2-HF) with gabapentin and ketamine. Streptozotocin-induced Diabetes Mellitus (DM) was used as a painful neuropathic model. Static and dynamic vulvodynia and allodynia were assessed using parameters including Flinching Response Threshold (FRT), Paw Withdrawal Threshold (PWT), Flinching Response Latency (FRL) and Paw withdrawal Latency (PWL) by applying the stimuli of Von Frey Filaments to the vulvar region and hind mid-planter regions of paws. A uniform quantity for five consecutive days post 29 days of MMG-10 % and control gel (1.0 mg/cm²) was applied three times daily (TDS) on vulvar area for vulvodynia and mid-plantar paws for allodynia studies. Safety with respect to sensorimotor functions was assessed via Rota rod and Balance beam tests. We conducted the vulvar histological tissue study to evaluate diabetes-induced structural damage and assess the therapeutic potential of a multimodal gel in tissue regeneration. Treatment with tested MMG 10 % resulted in a significant increase in FRT, PWT, FRL and PWL respectively (***p < 0.001, ** p < 0.01, p > 0.05) compared to the STZ treated group. Falling latency time was not affected in all treated groups exhibiting sensorimotor safety. The multimodal gel demonstrated significant regenerative efficacy by reducing atrophy, desquamation, and hyperkeratosis, effectively restoring vulvar tissue integrity in diabetic animals. Our MMG-10 %) could be potentially an effective therapeutic remedy for the relief against diabetes-induced vulvodynia and allodynia.