Shafiek Mena Z, Zaki Hala F, Mohamed Ahmed F
Department of Pharmacology and Toxicology, Faculty of Dentistry, Misr International University, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Fundam Clin Pharmacol. 2025 Feb;39(1):e13041. doi: 10.1111/fcp.13041. Epub 2024 Nov 4.
Fibromyalgia (FM) is a syndrome of pervasive chronic pain accompanied by low mood, sleep disorders, and cognitive decline. The dysfunction of central pain processing systems along with neurotransmitter disturbances are possible contributing mechanisms. Genetic polymorphism of the 𝛽2 adrenergic receptors is reported in FM patients. It is reported that chronic β2 agonists administration is effective for neuropathic pain alleviation. No current information, however, exists on their potential to alleviate nociplastic pain, such as FM. Therefore, the purpose of the current study is to examine salmeterol's potential antiallodynic effects in experimentally produced FM and explore some of the possible contributing mechanisms.
Thirty rats are allocated into three groups (n = 10): a normal group, a reserpine group that received reserpine (1 mg/kg; s.c.) for 3 days, and a reserpine + salmeterol group that received salmeterol (1 mg/kg; i.p.) for 21 consecutive days following last reserpine injection.
Reserpine administration resulted in behavioral and biochemical changes consistent with FM, including thermal and mechanical hyperalgesia, depressive behavior, and motor incoordination. This is coupled with disturbed spinal monoamine levels, depressed cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling, disturbed mitochondrial function/dynamics, and compromised blood-nerve barrier integrity. Treatment with salmeterol conceivably reversed these effects.
β2 receptor agonists such as salmeterol could be regarded as a promising strategy for the management of FM.
纤维肌痛(FM)是一种普遍存在的慢性疼痛综合征,伴有情绪低落、睡眠障碍和认知功能下降。中枢疼痛处理系统功能障碍以及神经递质紊乱可能是其潜在的致病机制。据报道,FM患者存在β2肾上腺素能受体的基因多态性。据报道,长期使用β2激动剂可有效缓解神经性疼痛。然而,目前尚无关于其缓解诸如FM等伤害性感受性疼痛的潜力的信息。因此,本研究的目的是检验沙美特罗在实验性诱导的FM中潜在的抗痛觉过敏作用,并探索一些可能的作用机制。
将30只大鼠分为三组(每组n = 10):正常组、接受利血平(1 mg/kg;皮下注射)3天的利血平组、在最后一次注射利血平后连续21天接受沙美特罗(1 mg/kg;腹腔注射)的利血平+沙美特罗组。
利血平给药导致与FM一致的行为和生化变化,包括热痛觉过敏和机械性痛觉过敏、抑郁行为和运动不协调。这伴随着脊髓单胺水平紊乱、环磷酸腺苷(cAMP)/蛋白激酶A(PKA)信号通路抑制、线粒体功能/动力学紊乱以及血神经屏障完整性受损。沙美特罗治疗可逆转这些效应。
沙美特罗等β2受体激动剂可被视为治疗FM的一种有前景的策略。