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Uncovering the Mechanisms of Adenosine Receptor-Mediated Pain Control: Focus on the A3 Receptor Subtype
- Source :
- International Journal of Molecular Sciences, Vol 22, Iss 7952, p 7952 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Agonists of the Gi protein-coupled A3 adenosine receptor (A3AR) have shown important pain-relieving properties in preclinical settings of several pain models. Active as a monotherapy against chronic pain, A3AR agonists can also be used in combination with classic opioid analgesics. Their safe pharmacological profile, as shown by clinical trials for other pathologies, i.e., rheumatoid arthritis, psoriasis and fatty liver diseases, confers a realistic translational potential, thus encouraging research studies on the molecular mechanisms underpinning their antinociceptive actions. A number of pathways, involving central and peripheral mechanisms, have been proposed. Recent evidence showed that the prototypical A3AR agonist Cl-IB-MECA and the new, highly selective, A3AR agonist MRS5980 inhibit neuronal (N-type) voltage-dependent Ca2+ currents in dorsal root ganglia, a known pain-related mechanism. Other proposed pathways involve reduced cytokine production, immune cell-mediated responses, as well as reduced microglia and astrocyte activation in the spinal cord. The aim of this review is to summarize up-to-date information on A3AR in the context of pain, including cellular and molecular mechanisms underlying this effect. Based on their safety profile shown in clinical trials for other pathologies, A3AR agonists are proposed as novel, promising non-narcotic agents for pain control.
- Subjects :
- 0301 basic medicine
Agonist
medicine.drug_class
QH301-705.5
T cells
Context (language use)
Catalysis
Inorganic Chemistry
03 medical and health sciences
0302 clinical medicine
dorsal root ganglion neurons
Ca2+ currents
medicine
A3 adenosine receptor
Physical and Theoretical Chemistry
Biology (General)
Molecular Biology
Adenosine A3 Receptor Agonists
QD1-999
Spectroscopy
neuropathic pain
business.industry
Organic Chemistry
Chronic pain
Visceral pain
General Medicine
medicine.disease
Adenosine receptor
Adenosine
Computer Science Applications
Chemistry
030104 developmental biology
Neuropathic pain
3
adenosine receptor
Ca
2+
currents
Dorsal root ganglion neurons
Interleukin-10
Animals
Astrocytes
Calcium Signaling
Humans
Microglia
Receptor, Adenosine A3
Ganglia, Spinal
Pain
visceral pain
medicine.symptom
business
Neuroscience
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 16616596 and 14220067
- Volume :
- 22
- Issue :
- 7952
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....b7b974704c106158f838752384bd4fa7