µ-Opioid Receptor Activation at the Dorsal Reticular Nucleus Shifts Diffuse Noxious Inhibitory Controls to Hyperalgesia in Chronic Joint Pain in Male Rats.
Anesthesiology
; 140(6): 1176-1191, 2024 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-38381969
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 µ-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 µ-opioid receptors and the phosphorylated forms of µ-opioid receptors and cAMP response element binding protein was quantified. Pharmacologic manipulation of µ-opioid receptors at the dorsal reticular nucleus was assessed in DNIC using the Randall-Selitto test.RESULTS:
At 42 days of monoarthritis, µ-opioid receptor labeling decreased at the dorsal reticular nucleus, while its phosphorylated form and the phosphorylated cAMP response element binding protein increased. [d-Ala2, N-Me-Phe4, Gly5-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 µ-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 µ-opioid receptor signaling to excitatory in this pathway likely accounts for the loss of DNIC analgesia in monoarthritis.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores Opioides mu
/
Artralgia
/
Dolor Crónico
/
Hiperalgesia
Límite:
Animals
Idioma:
En
Revista:
Anesthesiology
Año:
2024
Tipo del documento:
Article