?-Opioid Receptor Activation at the Dorsal Reticular Nucleus Shifts Diffuse Noxious Inhibitory Controls to Hyperalgesia in Chronic Joint Pain in Male Rats
Autores da FMUP
Participantes de fora da FMUP
- Teixeira-Pinto, Armando
- Silva, R.
Unidades de investigação
Abstract
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 Freunds 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.
Dados da publicação
- ISSN/ISSNe:
- 1528-1175, 0003-3022
- Tipo:
- Article
- Páginas:
- 1176-1191
- Link para outro recurso:
- www.scopus.com
Anesthesiology Lippincott Williams and Wilkins Ltd.
Citações Recebidas na Web of Science: 1
Citações Recebidas na Scopus: 1
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Keywords
- METABOLIC-ACTIVITY CHANGES; PRONOCICEPTIVE CENTER; FACILITATORY AREA; MORPHINE; NEURONS; BRAIN; PHOSPHORYLATION; DESENSITIZATION; RESPONSIVENESS; STIMULATION
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Citar a publicação
Neto F,Martins I,Teixeira A,Silva R. ?-Opioid Receptor Activation at the Dorsal Reticular Nucleus Shifts Diffuse Noxious Inhibitory Controls to Hyperalgesia in Chronic Joint Pain in Male Rats. Anesthesiology. 2024. 140. (6):p. 1176-1191. IF:8,800. (1).