Need to turn off the pain? Well now we can!
My sister suffers from chronic pain issues. I’ve written several posts about how her autoimmune disease is a special brand of pain that you will thankfully (almost certainly) never have to feel. While great strides have been made in pain management, there are still relatively few options that do not carry the risk of being extremely addictive. Well thankfully there is some new research and it offers hope, not just for my sister, but for the millions of people suffering from chronic pain that has been poorly managed.
Researchers 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.
The team demonstrated that turning on a receptor in the brain and spinal cord counteracts chronic nerve pain in male and female rodents. Activating the A3 receptor – either by its native chemical stimulator, the small molecule adenosine, or by powerful synthetic small molecule drugs invented at the NIH – prevents or reverses pain that develops slowly from nerve damage without causing analgesic tolerance or intrinsic reward (unlike opioids, which is frankly a really big deal).
Pain is an enormous problem and — for lack of a better way of putting it — is a pain. As an unmet medical need, pain causes suffering and comes with a multi-billion dollar societal cost. Current treatments are problematic because they cause intolerable side effects, diminish quality of life and do not sufficiently quell pain.
The most successful pharmacological approaches for the treatment of chronic pain rely on certain “pathways”: circuits involving opioid, adrenergic, and calcium channels.
For the past decade, scientists have tried to take advantage of these known pathways – the series of interactions between molecular-level components that lead to pain. While adenosine had shown potential for pain-killing in humans, researchers had not yet successfully leveraged this particular pain pathway because the targeted receptors engaged many side effects.
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.”
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.
All in all, this is a big deal. No one should have to live with chronic pain and the unfortunate side effects that come with heavy duty pain killers.
Little JW, Ford A, Symons-Liguori AM, Chen Z, Janes K, Doyle T, Xie J, Luongo L, Tosh DK, Maione S, Bannister K, Dickenson AH, Vanderah TW, Porreca F, Jacobson KA, & Salvemini D (2014). Endogenous adenosine A3 receptor activation selectively alleviates persistent pain states. Brain : a journal of neurology PMID: 25414036