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

Data de publicação:

Autores da FMUP

  • Fani Lourença Moreira Neto

    Autor

  • Maria Isabel Torres Martins

    Autor

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

Anesthesiology  Lippincott Williams and Wilkins Ltd.

Tipo:
Article
Páginas:
1176-1191
Link para outro recurso:
www.scopus.com

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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Opioid-induced hyperalgesia: is it a clinically relevant phenomenon? Critical appraisal of the literature.

Investigador Principal: Maria Isabel Torres Martins

Estudo Clínico Académico . 2022

Opioid-induced hyperalgesia: is it a clinically relevant phenomenon? Critical appraisal of the literature.

Investigador Principal: Maria Isabel Torres Martins

Estudo Clínico Académico . 2023

Opioidergic modulation of descending pain facilitation: Studies in models of neuropathic pain and opioid induced hyperalgesia

Investigador Principal: Maria Isabel Torres Martins

Estudo Clínico Académico . 2021

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