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This work was supported by MICINN Plan Nacional I + D + i [Grant number RT 2018-093677-B-100]. EC-M was supported by a Grant from MECD [FPU 15/02356].

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Cortes-Montero, ElsaAuthor

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December 19, 2022
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The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception

Publicated to:Molecular Brain. 13 (1): 150- - 2020-12-01 13(1), DOI: 10.1186/s13041-020-00676-4

Authors: Sanchez-Blazquez, Pilar; Cortes-Montero, Elsa; Rodriguez-Munoz, Maria; Merlos, Manuel; Garzon-Nino, Javier;

Affiliations

CSIC, Cajal Inst, Neuropharmacol, Doctor Arce 37, Madrid 28002, Spain - Author
Esteve, Drug Discovery & Preclin Dev, Barcelona, Spain - Author

Abstract

The Sigma-1 receptor (sigma 1R) 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 (sigma 2R) led us to investigate its potential role as a regulator of opioid analgesia and of pain hypersensitivity in sigma 2R knockout mice. In contrast to sigma 1R deficient mice, sigma 2R knockout mice developed mechanical allodynia following establishment of chronic constriction injury-induced neuropathic pain, which was alleviated by the sigma 1R antagonist S1RA. The analgesic effects of morphine, [D-Ala, N-MePhe, Gly-ol]-encephalin (DAMGO) and beta-endorphin increased in sigma 1R(-/-) mice and diminished in sigma 2R(-/-) mice. The analgesic effect of morphine was increased in sigma 2R(-/-) mice by treatment with S1RA. However, sigma 2R(-/-) 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 alpha 2-adrenergic receptor agonist clonidine. Therefore, while sigma R1 inhibits and sigma 2R 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.

Keywords

analgesiaknockout micemu opioid receptorneuropathic painsigma 1 receptorAnalgesiaAntagonistAntisense oligodeoxynucleotidesCloningExpressionHint1 proteinIdentificationInjectionKnockout miceModulationMu opioid receptorNeuropathic painSigma 1 receptorSigma 2 receptor

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Molecular Brain due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2020, it was in position 113/273, thus managing to position itself as a Q2 (Segundo Cuartil), in the category Neurosciences. Notably, the journal is positioned en el Cuartil Q2 para la agencia Scopus (SJR) en la categoría Molecular Biology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 3.59, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-21, the following number of citations:

  • WoS: 13
  • Scopus: 15

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-21:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 28.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 29 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 0.5.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).