Nociceptin/orphanin FQ receptor modulates painful and fatigue symptoms in a mouse model of fibromyalgia. Issue 6 (June 2019)

• Record Type: Journal Article
• Authors: Dagnino, Ana Paula Aquistapase; da Silva, Rodrigo Braccini Madeira; Chagastelles, Pedro Cesar; Pereira, Talita Carneiro Brandão; Venturin, Gianina Teribele; Greggio, Samuel; Costa da Costa, Jaderson; Bogo, Maurício Reis; Campos, Maria Martha
• Is Part Of: Pain. Volume 160:Issue 6(2019)
• Publication Date: 2019-06
• Subjects: Fibromyalgia -- Reserpine -- Nociceptin/orphanin FQ -- Nociceptin/orphanin FQ receptor -- UFP-101 -- SB-612111 -- Nociception -- Fatigue; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000001513
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Abstract: Generalized pain and fatigue are both hallmarks of fibromyalgia, a syndrome with an indefinite etiology. The treatment options for fibromyalgia are currently limited, probably because of its intricate pathophysiology. Thus, further basic and clinical research on this condition is currently needed. This study investigated the effects of nociceptin/orphanin FQ (N/OFQ) receptor (NOPr) ligands and the modulation of the NOP system in the preclinical mouse model of reserpine-induced fibromyalgia. The effects of administration of the natural agonist N/OFQ and the selective NOPr antagonists (UFP-101 and SB-612111) were evaluated in fibromyalgia-related symptoms in reserpine-treated mice. The expression of prepronociceptin/orphanin FQ and NOPr was assessed in central and peripheral sites at different time points after reserpine administration. Nociceptin/orphanin FQ displayed dual effects in the behavioral changes in the reserpine-elicited fibromyalgia model. The peptide NOPr antagonist UFP-101 produced analgesic and antifatigue effects, by preventing alterations in brain activity and skeletal muscle metabolism, secondary to fibromyalgia induction. The nonpeptide NOPr antagonist SB-612111 mirrored the favorable effects of UFP-101 in painful and fatigue alterations induced by reserpine. A time-related up- or downregulation of prepronociceptin/orphanin FQ and NOPr was observed in supraspinal, spinal, and peripheral sites of reserpine-treated mice. Our data shed new lights on the mechanisms underlying the fibromyalgia pathogenesis, supporting a role for N/OFQ-NOP receptor system in this syndrome. Abstract : Supplemental Digital Content is Available in the Text.We provide novel evidence showing the modulation of nociceptin/orphanin FQ receptor in a mouse model of fibromyalgia. Nociceptin/orphanin FQ receptor inhibition might represent an alternative for treating fibromyalgia symptoms.