Naderi Yeganeh, Soti Monavareh, Soltani Masoud, Naderi Yasaman, Kohlmeier Kristi A, Shabani Mohammad
Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.
Department of Drug Design and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Sci Rep. 2025 Aug 26;15(1):31335. doi: 10.1038/s41598-025-14820-4.
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.
本研究的目的是检验卡马西平（CBZ）与低剂量纳曲酮（LDN）联合使用对三叉神经痛（TN）的止痛效果，以减少CBZ的副作用以及协同抗痛觉过敏相互作用的可能性。雄性Wistar大鼠被随机分为8组：对照组、假手术组、TN组、TN（CBZ 100毫克）组、TN（CBZ 100毫克口服（p.o.）+LDN 0.5毫克，腹腔注射（i.p.））组、TN（CBZ 30毫克+LDN 0.5毫克）组、TN（CBZ 10毫克+LDN 0.5毫克）组和TN（LDN 0.5毫克）组。通过眶下神经慢性压迫损伤（CCI-ION）诱导TN。为了评估痛觉过敏，我们采用了von Frey、丙酮和吹气试验。使用旷场试验、高架十字迷宫试验、悬尾试验和被动回避试验评估认知功能。此外，在三叉神经脊髓核中测量总抗氧化能力水平（TAC）。与TN组相比，口服CBZ（100毫克）并联合LDN给药7天可显著降低CCI-ION诱导的机械性痛觉过敏，并改善焦虑、抑郁以及被动回避学习和记忆。LDN与CBZ联合给药比单独使用CBZ更有效地缓解焦虑和抑郁。与TN（CBZ100）组相比，TN（LDN）组表现出明显更好的回避记忆。与假手术组相比，TN组的TAC水平较低，而TN（CBZ 100+LDN）组和TN（LDN）组的TAC水平有所改善。数据表明，CBZ与LDN联合使用可有效降低TN大鼠的机械性痛觉过敏，而LDN还可能改善慢性TN疼痛引起的焦虑、抑郁和认知障碍。
