The development of drugs and other treatments for specific symptoms or conditions relies heavily on either serendipity (the chance finding of a beneficial effect) or on an understanding of underlying mechanisms. In pain, for example, there are limited ways in which we can block pain signals – such as activating opiate receptors or inhibiting prostaglandins. There are only so many ways in which you can interact with these systems. The discovery of a novel mechanism of modulating pain is therefore most welcome, and has the potential of leading to entirely new treatments that may have better side-effect profiles than existing treatments and also have additive clinical effects.
A recent study by Nana Goldman et. al., published in Nature Neuroscience, adds to our understanding of pain relief by identifying the role of adenosine in reducing pain activity in the peripheral nervous system. The researchers, in a nice series of experiments, demonstrated that producing a local painful stimulus in mice causes the local release of ATP (adenosine triphosphate) that peaks at about 30 minutes. This correlates with a decreased pain response in the mice. Further, if drugs are given that prolong the effect of adenosine, the analgesic effect itself is prolonged.
Also, if drugs are given that activate the adenosine A1 receptor, the observed analgesic effect is replicated. When these experiments are replicated in knockout mice that do not have the gene for the adenosine A1 receptor, there is no observed analgesic effect.
Together these experiments are fairly solid evidence that local pain results in the local release of adenosine that in turn binds to the adenosine A1 receptor inhibiting the pain response. This is potentially very exciting – it should lead to further investigation of the adenosine A1 receptor and the effects of activating and inhibiting it. This may lead to the development of drugs or other interventions that activate these receptors and may ultimately be a very useful addition to our ability to treat acute and chronic pain.