Supraspinal and Peripheral, but Not Intrathecal, σ1R Blockade by S1RA Enhances Morphine Antinociception

Conclusion In conclusion, the studies herein suggest that the σ1R antagonism enhances opioid antinociception in acute thermal pain conditions by the sum/integration of supraspinal and peripheral effects, through a mechanism independent of spinal NA levels. Ethics Statement All animal husbandry and experimental procedures complied with the European guidelines for the protection of animals used for experimental and other scientific purposes (Council Directive of 22 September 2010, 2010/63/EU), and were approved by the local Ethics Committee. Author Contributions AV-T, BF-P, and DZ designed and conducted the research. AV-T, AC, and BF-P performed the experiments. AV-T, JV, MM, and DZ wrote the main manuscript text. All authors analyzed the results and reviewed the manuscript. Funding The study has been supported by the Spanish Ministry of Economy, Industry and Competitiveness through the Centre for the Development of Industrial Technology (CDTI, IDI20130943). This study was partially funded by a Doctoral Research Grant awarded to AV-T by the Generalitat de Catalunya (AGAUR). Conflict of Interest Statement The authors of this article are employees of Esteve Pharmaceuticals. References Abadias, M., Escriche, M., Vaqué, A., Sust, M., and Encina, G. (2013). Safety, tolerability and pharmacokinetics of single and multiple doses of a novel sigma-1 receptor antagonist in three randomized phase I studies. Br. J. Clin. Pharmacol. 75, 103–117. doi: 10.111...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research