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Co-administration of low-dose-Naltrexone and Carbamazepine remarkedly ameliorate allodynia and cognitive deficit in a rat model of trigeminal neuralgia
Yeganeh Naderi, Monavareh Soti, Masoud Soltani, Yasaman Naderi, Kristi A. Kohlmeier & Mohammad Shabani
Scientific Reports volume 15, Article number: 31335 (26th August 2025)
https://www.nature.com/articles/s41598-025-14820-4
Abstract
The aim of this study was to examine the pain-relieving effects of combining Carbamazepine (CBZ) and low-dose-Naltrexone (LDN) in trigeminal neuralgia (TN) to reduce the side effects of CBZ and the potential of synergistic antiallodynic interaction. Male Wistar rats were allocated randomly to 8 groups: Control, Sham, TN, TN (CBZ 100 mg), TN (CBZ 100 mg oral (p.o.) + LDN 0.5 mg, intraperitoneal (i.p.)), TN (CBZ 30 mg + LDN 0.5 mg), TN (CBZ 10 mg + LDN 0.5 mg), and TN (LDN 0.5 mg). TN was induced through chronic constriction injury of the infraorbital nerve (CCI-ION) . To evaluate hyperalgesia, we employed the von Frey, acetone, and air puff tests. Cognitive functions were assessed using the open field, elevated plus maze, tail suspension, and passive avoidance tests. Furthermore, total antioxidant capacity levels (TAC) were measured in the spinal trigeminal nucleus. Administering oral CBZ (100 mg) along with LDN for 7 days significantly reduced CCI-ION-induced mechanical allodynia and improved anxiety, depression, and passive avoidance learning and memory compared to the TN group. Co-administration of LDN and CBZ more effectively alleviated anxiety and depression than CBZ alone. The TN (LDN) group demonstrated significantly better avoidance memory compared to the TN (CBZ100) group. The TN group exhibited a lower TAC level compared to the sham group, and TAC levels were improved in the TN (CBZ 100 + LDN) and TN (LDN) groups. The data indicate that combining CBZ with LDN effectively reduces mechanical allodynia in TN rats, while LDN may also improve anxiety, depression, and cognitive impairment caused by chronic TN pain.