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SIGMA-1 (Σ1) RECEPTOR ANTAGONISTS POTENTIATE THE ANALGESIA INDUCED BY MORPHINE

At the 2017 EFIC one poster highlighted the possible function of the Sigma-1 receptors in pain, and especially in visceral pain.

Visceral pain is a major clinical problem. Sigma-1 receptors (σ1R) potentiate the morphine-induced analgesia in somatic pain models.
The researchers have confirmed that σ1R are involved in visceral pain but the morphine modulation in visceral pain is unexplored.

The purpose of this study was to determine the potential use of σ1R antagonists associated to morphine as a potential strategy for treating visceral pain. We performed studies in the intracolonic capsaicin-induced visceral pain model using female wild-type (WT) and σ1R knockout (σ1R-KO) mice.

Drugs used were: the σ1R antagonists NE-100, BD-1063 and BD-1047; morphine, naloxone and naloxone methiodide (a peripherally restricted opioid antagonist).

Capsaicin (0.1%) was instilled into the colon via the anus and the pain-related behaviors were counted for 20 min and afterwards, the referred mechanical hyperalgesia was recorded using von Frey filaments.

In WT mice, the effect of 2 mg/kg of morphine, a dose that produces a moderate reduction of pain behaviors but has no analgesic effects in mechanical hyperalgesia, was enhanced by all the σ1R antagonists evaluated.

Naloxone (1 mg/kg) fully reversed the morphine potentiation induced by the σ1R antagonists in both types of pain, whereas naloxone methiodide (2 mg/kg) totally abolished the referred pain but only partially the acute pain.

None of the σ1R antagonists potentiated the morphine-induced effect in σ1R-KO mice.

These results suggest that σ1R antagonists might play a role in increasing morphine analgesia, providing a therapeutic approach to visceral pain treatment.

P01-BASIC SCIENCE (ANATOMY, PHYSIOLOGY, PHARMACOLOGY, BEHAVIOUR): ANIMAL PAIN MODELS
Abstract: 302
SIGMA-1 (Σ1) RECEPTOR ANTAGONISTS POTENTIATE THE ANALGESIA INDUCED BY MORPHINE IN A MODEL OF VISCERAL PAIN IN MICE
A. Artacho-Cordon1, L. Romero1, E. Portillo-Salido2, C.M. Cendan1, J.M. Baeyens1
1Neuroscience Institute, Pharmacology, Armilla-Granada, Spain
2Esteve Laboratories, Esteve, Barcelona, Spain