Suárez-Rojas Irene, Pérez-Fernández Montse, Bai Xue, Martínez-Martel Ignacio, Intagliata Sebastiano, Pittalà Valeria, Salerno Loredana, Pol Olga
Grup de Neurofarmacologia Molecular, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain.
Grup de Neurofarmacologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.
Antioxidants (Basel). 2023 Oct 13;12(10):1859. doi: 10.3390/antiox12101859.
Neuropathic pain is a type of pain that persists for a long time and becomes pathological. Additionally, the anxiodepressive disorders derived from neuropathic pain are difficult to palliate with the current treatments and need to be resolved. Then, using male mice with neuropathic pain provoked by chronic constriction of the sciatic nerve (CCI), we analyzed and compared the analgesic actions produced by three new heme oxygenase 1 (HO-1) inducers, 1m, 1b, and 1a, with those performed by dimethyl fumarate (DMF). Their impact on the anxiety- and depressive-like comportments and the expression of the inflammasome NLRP3, Nrf2, and some antioxidant enzymes in the dorsal root ganglia (DRG) and amygdala (AMG) were also investigated. Results revealed that the administration of 1m, 1b, and DMF given orally for four days inhibited the allodynia and hyperalgesia caused by CCI, while 1a merely reduced the mechanical allodynia. However, in the first two days of treatment, the antiallodynic effects produced by 1m were higher than those of 1a and DMF, and its antihyperalgesic actions were greater than those produced by 1b, 1a, and DMF, revealing that 1m was the most effective compound. At four days of treatment, all drugs exerted anxiolytic and antidepressant effects, decreased the NLRP3 levels, and increased/normalized the Nrf2, HO-1, and superoxide dismutase 1 levels in DRG and AMG. Data indicated that the dual modulation of the antioxidant and inflammatory pathways produced by these compounds, especially 1m, is a new promising therapeutic approach for neuropathic pain and related emotional illnesses.
神经性疼痛是一种持续时间长且已病变的疼痛类型。此外，由神经性疼痛引发的焦虑抑郁障碍难以通过当前治疗方法缓解，需要加以解决。于是，我们使用坐骨神经慢性缩窄（CCI）诱发神经性疼痛的雄性小鼠，分析并比较了三种新型血红素加氧酶1（HO-1）诱导剂1m、1b和1a与富马酸二甲酯（DMF）产生的镇痛作用。还研究了它们对焦虑样和抑郁样行为以及背根神经节（DRG）和杏仁核（AMG）中炎性小体NLRP3、Nrf2和一些抗氧化酶表达的影响。结果显示，连续四天口服1m、1b和DMF可抑制CCI引起的痛觉过敏和痛觉超敏，而1a仅减轻机械性痛觉过敏。然而，在治疗的前两天，1m产生的抗痛觉过敏作用高于1a和DMF，其抗痛觉超敏作用大于1b、1a和DMF，表明1m是最有效的化合物。在治疗四天时，所有药物均发挥抗焦虑和抗抑郁作用，降低了NLRP3水平，并使DRG和AMG中的Nrf2、HO-1和超氧化物歧化酶1水平升高/恢复正常。数据表明，这些化合物，尤其是1m，对抗氧化和炎症途径的双重调节是治疗神经性疼痛及相关情绪疾病的一种新的有前景的治疗方法。
