Title:Benzimidazole Derivative Ameliorates Opioid-Mediated Tolerance during Anticancer- Induced Neuropathic Pain in Mice
VOLUME: 21 ISSUE: 3
Author(s):Sana Akhtar, Muzaffar Abbas*, Komal Naeem, Muhammad Faheem, Humaira Nadeem and Amber Mehmood
Affiliation:Department of Basic Medical Sciences, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Department of Pharmacy, Capital University of Science and Technology, Islamabad, Department of Basic Medical Sciences, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Department of Basic Medical Sciences, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Department of Pharmaceutical Chemistry, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Department of Basic Medical Sciences, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad
Keywords:Cisplatin, neuropathic pain, nalbuphine, tolerance, TNF-α, benzimidazole derivative.
Abstract:
Background: Cancer is known to be the second significant cause of death worldwide. Chemotherapeutic
agents such as platinum-based compounds are frequently used single-handedly or accompanied by additional
chemotherapies to treat cancer patients. Chemotherapy-induced peripheral painful neuropathy is seen in
around 40% of patients who are treated with platinum-based compounds, including cisplatin. This not only
decreases the quality of life of patients but also patients’ compliance with cisplatin.
Objectives: Nalbuphine, an opioid, is frequently used to treat acute and chronic pain, coupled with cisplatin in
cancer patients. However, long term use of nalbuphine induces tolerance to its analgesic effects. We employed
the same strategy to induce tolerance in mice.
Methods: Here, we investigated analgesic effects of 2-[(pyrrolidin-1-yl) methyl]-1H-benzimidazole (BNZ), a
benzimidazole derivative, on nalbuphine-induced tolerance during cisplatin-induced neuropathic pain using hot
plate test, tail-flick tests and von Frey filament in mouse models. Furthermore, we investigated the effects of
BNZ on the expression of Tumor Necrosis Factor-alpha (TNF-α) in the spinal cord.
Results: The results showed that BNZ reduced tolerance to analgesic effects of nalbuphine and TNF-α expression
in mice.
Conclusion: BNZ could be a potential drug candidate for the management of nalbuphine-induced tolerance in
cisplatin-induced neuropathic pain.
