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The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception

AuthorsSánchez-Blázquez, Pilar ; Cortés-Montero, Elsa; Rodríguez-Muñoz, María; Garzón-Niño, Javier
KeywordsSigma 2 receptor
Sigma 1 receptor
Knockout mice
Mu opioid receptor
Neuropathic pain
Issue Date11-Nov-2020
PublisherBioMed Central
CitationMolecular Brain 13 (2020)
AbstractThe Sigma-1 receptor (σ1R) has emerged as an interesting pharmacological target because it inhibits analgesia mediated by mu-opioid receptors (MOR), and also facilitates the development of neuropathic pain. Based on these findings, the recent cloning of the Sigma-2 receptor (σ2R) led us to investigate its potential role as a regulator of opioid analgesia and of pain hypersensitivity in σ2R knockout mice. In contrast to σ1R deficient mice, σ2R knockout mice developed mechanical allodynia following establishment of chronic constriction injury-induced neuropathic pain, which was alleviated by the σ1R antagonist S1RA. The analgesic effects of morphine, [D-Ala, N-MePhe, Gly-ol]-encephalin (DAMGO) and β-endorphin increased in σ1R mice and diminished in σ2R mice. The analgesic effect of morphine was increased in σ2R mice by treatment with S1RA. However, σ2R mice and wild-type mice exhibited comparable antinociceptive responses to the delta receptor agonist [D-Pen2,5]-encephalin (DPDPE), the cannabinoid type 1 receptor agonist WIN55,212-2 and the α2-adrenergic receptor agonist clonidine. Therefore, while σR1 inhibits and σ2R facilitates MOR-mediated analgesia these receptors exchange their roles when regulating neuropathic pain perception. Our study may help identify new pharmacological targets for diminishing pain perception and improving opioid detoxification therapies.
Publisher version (URL)http://dx.doi.org/10.1186/s13041-020-00676-4
Identifiersdoi: 10.1186/s13041-020-00676-4
issn: 1756-6606
Appears in Collections:(IC) Artículos
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