μ-Opioid Receptor Activation at the Dorsal Reticular Nucleus Shifts Diffuse Noxious Inhibitory Controls to Hyperalgesia in Chronic Joint Pain in Male Rats

• Tipo: Artigo em Revista Científica Internacional
• Data: 2024

Autores

Pereira-Silva, Raquel (Autor) Outra; Teixeira-Pinto, Armando (Autor) Outra; Neto, Fani L (Autor) FMUP; Martins, Isabel (Autor) FMUP

Revista

Título: Anesthesiology

Vol. 140

Páginas: 1176-1191

ISSN: 0003-3022

Editora: Wolters Kluwer Health

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 0 Citações

Outras Informações

ID Authenticus: P-010-EBA

DOI: 10.1097/aln.0000000000004956

Abstract (EN): Background: The dorsal reticular nucleus is a pain facilitatory area involved in diffuse noxious inhibitory control (DNIC) through opioidergic mechanisms that are poorly understood. The hypothesis was that signaling of mu-opioid receptors is altered in this area with prolonged chronic inflammatory pain and that this accounts for the loss of DNICs occurring in this condition. Methods: Monoarthritis was induced in male Wistar rats (n = 5 to 9/group) by tibiotarsal injection of complete Freund's adjuvant. The immunolabeling of mu -opioid receptors and the phosphorylated forms of mu -opioid receptors and cAMP response element binding protein was quantified. Pharmacologic manipulation of mu-opioid receptors at the dorsal reticular nucleus was assessed in DNIC using the Randall-Selitto test. Results: At 42 days of monoarthritis, mu-opioid receptor labeling decreased at the dorsal reticular nucleus, while its phosphorylated form and the phosphorylated cAMP response element binding protein increased. [d-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin acetate (DAMGO) enhanced DNIC analgesia in normal animals (means +/- SD: pre-DNIC: 126.9 +/- 7.0 g; DNIC - DAMGO: 147.5 +/- 8.0 g vs. DNIC + DAMGO: 198.1 +/- 19.3 g; P < 0.001), whereas it produced hyperalgesia in monoarthritis (pre-DNIC: 67.8 +/- 7.5 g; DNIC - DAMGO: 70.6 +/- 7.7 g vs. DNIC + DAMGO: 32.2 +/- 2.6 g; P < 0.001). An ultra-low dose of naloxone, which prevents the excitatory signaling of the mu-opioid receptor, restored DNIC analgesia in monoarthritis (DNIC - naloxone: 60.0 +/- 6.1 g vs. DNIC + naloxone: 98.0 +/- 13.5 g; P < 0.001), compared to saline (DNIC - saline: 62.5 +/- 5.2 g vs. DNIC + saline: 64.2 +/- 3.8 g). When injected before DAMGO, it restored DNIC analgesia and decreased the phosphorylated cAMP response element binding protein in monoarthritis. Conclusions: The dorsal reticular nucleus is likely involved in a facilitatory pathway responsible for DNIC hyperalgesia. The shift of mu-opioid receptor signaling to excitatory in this pathway likely accounts for the loss of DNIC analgesia in monoarthritis.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 16