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Objectives <p>Diabetic neuropathy is a severe diabetic complication that causes hyperalgesia, allodynia and vulvodynia in diabetic female patients. Modern-day pharmaceutical therapies, consisting of topical medications, opioids, GABA analogues, and antidepressants, have the disadvantage of causing systemic adverse effects and poor adherence, while providing only partial alleviation from the symptoms of neuropathy. This study was aimed to assess the preclinical efficacy of carbopol-940 based multimodal topical gel combining 3-hydroxyflavone (3-HF), gabapentin, and ketamine in streptozotocin (STZ) induced diabetic neuropathy to fill the therapeutic gap.</p> Methods <p>10% Gabapentin gel (GG-10%) and a control gel (CG) were used in contrast to test the effects of a 10% multimodal test gel (MMTG-10%) in female rats. The Flinching Response Threshold (FRT), Paw Withdrawal Threshold (PWT), Flinching Response Latency (FRL), and Paw Withdrawal Latency (PWL) were exploited to assess the responses to pain using von Frey filaments applied to the hind paw and vulva region. Vulvar tissues were subjected to histopathological examination.</p> Results <p>The 10% MMTG produced significant changes (rise) in FRT, PWT, FRL, and PWL as compared to gabapentin gel and control gel. A major drop was seen in PWD (***<i>p</i> &lt; 0.001) when treated with 10% MMTG in comparison to the diseased control group (DC) whereas the 10% GG-10% produced less effect in reducing PWD and CG produced no effect in reducing PWD. Histopathological evaluation revealed that there was a reduction in atrophy, desquamation, and hyperkeratosis and restoration of vulvar architecture.</p> Conclusion <p>Our findings indicated that the MMTG-10% proves to be a promising therapeutic approach for diabetes-induced neuropathic pain, particularly for vulvodynia, by promoting tissue regeneration and providing additional analgesic efficacy. This approach could lower the healthcare expenses for chronic diabetic problems and makes a patient’s life better.</p>

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Evaluation of 3-Hydroxyflavone, Gabapentin, and Ketamine Based Anti-Neuropathic Gel: Preclinical Anti-Nociceptive, Vulvar Tissue-Regenerative Studies

  • 期刊论文

  • 发表日期：

    2026年3月11日

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  • Jibran Qayyum,
  • Gowhar Ali,
  • Elham Saleh Albalawi,
  • Mushtaq Ahmad Mir,
  • Nasreena Bashir,
  • Pordil Khan,
  • Fatima Ayyaz,
  • Emaan khurshid,
  • Muhammad Ayaz

摘要

Objectives

Diabetic neuropathy is a severe diabetic complication that causes hyperalgesia, allodynia and vulvodynia in diabetic female patients. Modern-day pharmaceutical therapies, consisting of topical medications, opioids, GABA analogues, and antidepressants, have the disadvantage of causing systemic adverse effects and poor adherence, while providing only partial alleviation from the symptoms of neuropathy. This study was aimed to assess the preclinical efficacy of carbopol-940 based multimodal topical gel combining 3-hydroxyflavone (3-HF), gabapentin, and ketamine in streptozotocin (STZ) induced diabetic neuropathy to fill the therapeutic gap.

Methods

10% Gabapentin gel (GG-10%) and a control gel (CG) were used in contrast to test the effects of a 10% multimodal test gel (MMTG-10%) in female rats. The Flinching Response Threshold (FRT), Paw Withdrawal Threshold (PWT), Flinching Response Latency (FRL), and Paw Withdrawal Latency (PWL) were exploited to assess the responses to pain using von Frey filaments applied to the hind paw and vulva region. Vulvar tissues were subjected to histopathological examination.

Results

The 10% MMTG produced significant changes (rise) in FRT, PWT, FRL, and PWL as compared to gabapentin gel and control gel. A major drop was seen in PWD (***p < 0.001) when treated with 10% MMTG in comparison to the diseased control group (DC) whereas the 10% GG-10% produced less effect in reducing PWD and CG produced no effect in reducing PWD. Histopathological evaluation revealed that there was a reduction in atrophy, desquamation, and hyperkeratosis and restoration of vulvar architecture.

Conclusion

Our findings indicated that the MMTG-10% proves to be a promising therapeutic approach for diabetes-induced neuropathic pain, particularly for vulvodynia, by promoting tissue regeneration and providing additional analgesic efficacy. This approach could lower the healthcare expenses for chronic diabetic problems and makes a patient’s life better.