Inhibitors of angiotensin I converting enzyme potentiate fibromyalgia-like pain symptoms via kinin receptors in mice

Published on Jan 18, 2021in European Journal of Pharmacology4.432
· DOI :10.1016/J.EJPHAR.2021.173870
Indiara Brusco11
Estimated H-index: 11
(UFSM: Universidade Federal de Santa Maria),
Allisson Benatti Justino10
Estimated H-index: 10
(UFU: Federal University of Uberlandia)
+ 3 AuthorsSara Marchesan Oliveira28
Estimated H-index: 28
(UFSM: Universidade Federal de Santa Maria)
Sources
Abstract
Fibromyalgia is a potentially disabling chronic disease, characterized by widespread pain and a range of comorbidities such as hypertension. Among the mechanisms involved in fibromyalgia-like pain symptoms are kinins and their B1 and B2 receptors. Moreover, angiotensin I converting enzyme (ACE) inhibitors, commonly used as antihypertensive drugs, can enhance pain by blocking the degradation of peptides such as substance P and bradykinin, besides enhancing kinin receptors signalling. We investigated the effect of ACE inhibitors on reserpine-induced fibromyalgia-like pain symptoms and the involvement of kinins in this effect in mice. Nociceptive parameters (mechanical and cold allodynia and overt nociception) were evaluated after ACE inhibitors administration in mice previously treated with reserpine. The role of kinin B1 and B2 receptors was investigated using pharmacological antagonism. Additionally, bradykinin levels, as well as the activity of ACE and kininase I, were measured in the sciatic nerve, spinal cord and cerebral cortex of the mice. The ACE inhibitors enalapril and captopril enhanced reserpine-induced mechanical allodynia, and this increase was prevented by kinin B1 and B2 receptor antagonists. Substance P and bradykinin caused overt nociception and increased mechanical allodynia in animals treated with reserpine. Reserpine plus ACE inhibitors increased bradykinin-related peptide levels and inhibited ACE activity in pain modulation structures. Since hypertension is a frequent comorbidity affecting fibromyalgia patients, hypertension treatment with ACE inhibitors in these patients should be reviewed once this could enhance fibromyalgia-like pain symptoms. Thus, the treatment of hypertensive patients with fibromyalgia could include other classes of antihypertensive drugs, different from ACE inhibitors.
References64
Newest
#1Indiara Brusco (UFSM: Universidade Federal de Santa Maria)H-Index: 11
#2Allisson Benatti Justino (UFU: Federal University of Uberlandia)H-Index: 10
Last. Sara Marchesan Oliveira (UFSM: Universidade Federal de Santa Maria)H-Index: 28
view all 9 authors...
Abstract Fibromyalgia is a disease characterised as generalised chronic primary pain that causes functional disability and a reduction in patients' quality of life, without specific pathophysiology or appropriate treatment. Previous studies have shown that kinins and their B 1 and B 2 receptors contribute to chronic painful conditions. Thus, we investigated the involvement of kinins and their B 1 and B 2 receptors in a fibromyalgia-like pain model induced by reserpine in mice. Nociceptive parame...
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#1Edita Navratilova (UA: University of Arizona)H-Index: 27
#2Frank Porreca (UA: University of Arizona)H-Index: 116
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Document reviewers: Guy De Backer (ESC Review Co-ordinator) (Belgium), Anthony M. Heagerty (ESH Review Co-ordinator) (UK), Stefan Agewall (Norway), Murielle Bochud (Switzerland), Claudio Borghi (Italy), Pierre Boutouyrie (France), Jana Brguljan (Slovenia), Hector Bueno (Spain), Enrico G. Caiani (Ita
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#1Geoffrey O. Littlejohn (Monash University)H-Index: 46
#2Emma Kathryn Guymer (Monash University)H-Index: 11
Fibromyalgia is a high impact chronic pain disorder with a well-defined and robust clinical phenotype. Key features include widespread pain and tenderness, high levels of sleep disturbance, fatigue, cognitive dysfunction and emotional distress. Abnormal processing of pain and other sensory input occurs in the brain, spinal cord and periphery and is related to the processes of central and peripheral sensitization. As such, fibromyalgia is deemed to be one of the central sensitivity syndromes. The...
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#1Indiara Brusco (UFSM: Universidade Federal de Santa Maria)H-Index: 11
#2Cássia Regina Silva (UFSM: Universidade Federal de Santa Maria)H-Index: 22
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Paclitaxel is a chemotherapeutic agent used to treat solid tumours. However, it causes an acute and neuropathic pain syndrome that limits its use. Among the mechanisms involved in neuropathic pain caused by paclitaxel is activation of kinin receptors. Angiotensin converting enzyme (ACE) inhibitors can enhance kinin receptor signalling. The goal of this study was to evaluate the role of kinins on paclitaxel-associated acute pain syndromes (P-APS) and the effect of ACE inhibition on P-APS and pacl...
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#2Camila Camponogara (UFSM: Universidade Federal de Santa Maria)H-Index: 10
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Last. Enrique J. CobosH-Index: 25
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Objective The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were ‘expert opinion’. Methods A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pa...
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#1Rafael C. Dutra (UFSC: Universidade Federal de Santa Catarina)H-Index: 28
The central function of the immune system is to protect the host from environmental agents such as microbes or chemicals, thereby preserving the integrity of the body, and preventing the onset of illness and infection. Moreover, the immune system is constantly challenged to discriminate self vs. non-self and mediate the correct response, a phenomenon called self-tolerance. The failure of mechanisms responsible for self-tolerance and induction of an immune response against components of the self,...
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#1Sara Marchesan Oliveira (UFSM: Universidade Federal de Santa Maria)H-Index: 28
#2Cássia Regina Silva (UFSM: Universidade Federal de Santa Maria)H-Index: 22
Last. Juliano Ferreira (UFSC: Universidade Federal de Santa Catarina)H-Index: 54
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Fibromyalgia (FM) is a complex syndrome, with an indefinite aetiology and intricate pathophysiology that affects 2 - 3% of the world population. From the beginning of the 2000s, experimental animal models have been developed to mimic clinical FM and help obtain a better understanding of the relevant neurobiology. These animal models have enabled a broad study of FM symptoms and mechanisms, as well as new treatment strategies. Current experimental FM models include the reserpine-induced systemic ...
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