'Off switch' for pain discovered

'Off switch' for pain discovered: Activating the adenosine A3 receptor subtype is key to powerful pain relief -- ScienceDaily

In research published in the medical journal Brain, by Saint Louis University Medical Center researcher Daniela Salvemini, Ph.D. and colleagues within SLU, the National Institutes of Health (NIH) and other academic institutions have discovered a way to block a pain pathway in animal models of chronic neuropathic pain including pain caused by chemotherapeutic agents and bone cancer pain suggesting a promising new approach to pain relief.

A Key to Pain Relief

Simplified illustration of extracellular purinergic signalling

In this research, Salvemini and colleagues have demonstrated that activation of the A3 adenosine receptor subtype is key in mediating the pain relieving effects of adenosine.
"It has long been appreciated that harnessing the potent pain-killing effects of adenosine could provide a breakthrough step towards an effective treatment for chronic pain," Salvemini said. "Our findings suggest that this goal may be achieved by focusing future work on the A3AR pathway, in particular, as its activation provides robust pain reduction across several types of pain."

Pharmacologic Characterization of CA200645, A3AR Agonist

Researchers are excited to note that A3AR agonists are already in advanced clinical trials as anti-inflammatory and anticancer agents and show good safety profiles. "These studies suggest that A3AR activation by highly selective small molecular weight A3AR agonists such as MRS5698 activates a pain-reducing pathway supporting the idea that we could develop A3AR agonists as possible new therapeutics to treat chronic pain," Salvemini said.

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Endogenous adenosine A3 receptor activation selectively alleviates persistent pain states | Brain

1. J. W. Little, A. Ford, A. M. Symons-Liguori, Z. Chen, K. Janes, T. Doyle, J. Xie, L. Luongo, D. K. Tosh, S. Maione, K. Bannister, A. H. Dickenson, T. W. Vanderah, F. Porreca, K. A. Jacobson, D. Salvemini. Endogenous adenosine A3 receptor activation selectively alleviates persistent pain states. Brain, 2014; DOI: 10.1093/brain/awu330 
2. Pnina Fishman and Sara Bar-Yehuda, Pharmacology and Therapeutic Applications of A3 ReceptorSubtype, Current Topics in Medicinal Chemistry, 2003, 3, 463-469 1568-0266/03 $41.00+.00 © 2003 Bentham Science Publishers Ltd. 
3. In Vivo Phenotypic Screening for Treating Chronic Neuropathic Pain: Modification of C2-Arylethynyl Group of Conformationally Constrained A3 Adenosine Receptor Agonists - Journal of Medicinal Chemistry (ACS Publications)
4. Adenosine receptor subtype 3 (A3AR) agonists as novel analgesics in chronic neuropathic pain -- Salvemini et al. 27 (1): 887.1 -- The FASEB Journal
5. Turning off Chronic Pain: New Study Provides Hope for Sufferers : Drugs/Therapy : Counsel & Heal 
6. SLU researcher finds an off switch for pain
7. Fragment Screening at Adenosine-A3 Receptors in Living Cells Using a Fluorescence-Based Binding Assay: Chemistry & Biology 
8. Structure-guided design of A(3) adenosine receptor-selective nucleo... - PubMed - NCBI
9. Need to turn off the pain? Well now we can! | Loony Labs