Modulation by Sigma-1 Receptor of Morphine Analgesia and Tolerance: Nociceptive Pain, Tactile Allodynia and Grip Strength Deficits During Joint Inflammation
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AuthorMontilla-García, Ángeles; Tejada, Miguel Ángel; Ruiz Cantero, M. Carmen; Bravo Caparrós, Inmaculada; Yeste, Sandra; Zamanillo, Daniel; Cobos, Enrique J.
Sigma-1 receptorsMorphineAnalgesiaJoint inflammationGrip strength
Montilla-García Á, Tejada MÁ, Ruiz-Cantero MC, Bravo-Caparrós I, Yeste S, Zamanillo D and Cobos EJ (2019) Modulation by Sigma-1 Receptor of Morphine Analgesia and Tolerance: Nociceptive Pain, Tactile Allodynia and Grip Strength Deficits During Joint Inflammation. Front. Pharmacol. 10:136.
SponsorshipMT was supported by a postdoctoral grant from the University of Granada.MR-C and IB-C were supported by FPU grants from the Spanish Ministry of Economy and Competitiveness (MINECO). This study was partially supported by the Spanish Ministry of Economy and Competitiveness (Grants SAF2013-47481P and SAF2016-80540-R), the Junta de Andalucía (Grant CTS109), and FEDER funds.
Sigma-1 receptor antagonism increases the effects of morphine on nociceptive pain, even in morphine-tolerant animals. However, it is unknown whether these receptors are able to modulate morphine antinociception and tolerance during inflammatory pain. Here we used a mouse model to test the modulation of morphine effects by the selective sigma-1 antagonist S1RA (MR309), by determining its effect on inflammatory tactile allodynia (von Frey filaments) and on grip strength deficits induced by joint inflammation (a measure of pain-induced functional disability), and compared the results with those for nociceptive heat pain recorded with the unilateral hot plate (55 C) test. The subcutaneous (s.c.) administration of morphine induced antinociceptive effects to heat stimuli, and restored mechanical threshold and grip strength in mice with periarticular inflammation induced by Complete Freund’s Adjuvant. S1RA (80 mg/kg, s.c.) administered alone did not induce any effect on nociceptive heat pain or inflammatory allodynia, but was able to partially reverse grip strength deficits. The association of S1RA with morphine, at doses inducing little or no analgesic-like effects when administered alone, resulted in a marked antinociceptive effect to heat stimuli and complete reversion of inflammatory tactile allodynia. However, S1RA administration did not increase the effect of morphine on grip strength deficits induced by joint inflammation.