Sigma-1 receptor: A drug target for the modulation of neuroimmune and neuroglial interactions during chronic pain. (January 2021)

• Record Type: Journal Article
• Authors: Ruiz-Cantero, M. Carmen; González-Cano, Rafael; Tejada, Miguel Á.; Santos-Caballero, Miriam; Perazzoli, Gloria; Nieto, Francisco R.; Cobos, Enrique J.
• Is Part Of: Pharmacological research. Volume 163(2021)
• Publication Date: 2021-01
• Subjects: ATP adenosine triphosphate -- BDNF brain-derived neurotrophic factor -- CX3CL1 C-X3-C Motif Chemokine Ligand 1 -- CCL-2 C-C Motif Chemokine Ligand 2 -- Cx43 connexin 43 -- DRG dorsal root ganglia -- GDNF glial-derived neurotrophic factor -- IL interleukin -- MCP1 monocyte chemoattractant protein-1 -- MRI magnetic resonance imaging -- NGF nerve growth factor -- NMDA N-methyl-D-aspartate -- PET positron emission tomography -- TNF tumor necrosis factor; Pain -- Endogenous opioid analgesia -- Neuroinflammation -- Macrophage -- Microglia -- Astrocyte; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.105339
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Highlights: Sigma-1 antagonism enhances immune-driven opioid analgesia during inflammation. Inhibition of sigma-1 receptors decreases neuroinflammation in the DRG. Sigma-1 receptor antagonism inhibits neuroinflammation in the brain and spinal cord. Sigma-1 antagonists may constitute a new class of analgesics. Abstract: Immune and glial cells play a pivotal role in chronic pain. Therefore, it is possible that the pharmacological modulation of neurotransmission from an exclusively neuronal perspective may not be enough for adequate pain management, and the modulation of complex interactions between neurons and other cell types might be needed for successful pain relief. In this article, we review the current scientific evidence for the modulatory effects of sigma-1 receptors on communication between the immune and nervous systems during inflammation, as well as the influence of this receptor on peripheral and central neuroinflammation. Several experimental models of pathological pain are considered, including peripheral and central neuropathic pain, osteoarthritic, and cancer pain. Sigma-1 receptor inhibition prevents peripheral (macrophage infiltration into the dorsal root ganglion) and central (activation of microglia and astrocytes) neuroinflammation in several pain models, and enhances immune-driven peripheral opioid analgesia during painful inflammation, maximizing the analgesic potential of peripheral immune cells. Therefore, sigma-1 antagonists may constitute a new class of analgesics with an unprecedented mechanism of action and potential utility in several painful disorders.