nalbuphine and Neuralgia

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.. 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.. 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.. The results showed that BNZ reduced tolerance to analgesic effects of nalbuphine and TNF-α expression in mice.. BNZ could be a potential drug candidate for the management of nalbuphine-induced tolerance in cisplatin-induced neuropathic pain.

Topics: Analgesics, Opioid; Animals; Antineoplastic Agents; Benzimidazoles; Cisplatin; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Drug Tolerance; Male; Mice; Molecular Structure; Nalbuphine; Neuralgia; Structure-Activity Relationship

Neurotoxicity is frequent with vincristine treatment, but severe autonomic neuropathy is rare. A decreased activity of drug transporters in the presence of an interacting drug may favor such events by increasing systemic or tissue exposure to the drug. We encountered severe autonomic neuropathy and cholestasis in a child receiving vincristine, after the introduction of piperacillin-tazobactam. A causality assessment of the adverse reaction identified the antibiotic as the most probable cause of the observation. The patient was heterozygous for several common polymorphisms of ABCC2 (multidrug-related protein-2), CYP3A5, and ABCB1 (multidrug-related protein-1, P-glycoprotein), but their role in the toxicity cannot be ascertained.

Topics: Abdominal Pain; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Autonomic Nervous System Diseases; Biological Transport; Child; Cholestasis; Cyclophosphamide; Cytochrome P-450 CYP3A; Daunorubicin; Drug Combinations; Drug Interactions; Facial Pain; Female; Humans; Intestinal Obstruction; Intestinal Pseudo-Obstruction; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Nalbuphine; Neoplasm Proteins; Neuralgia; Penicillanic Acid; Piperacillin; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Seizures; Tazobactam; Vincristine