How pain comes and goes

Pain is an unpleasant feeling often caused by intense or damaging stimuli as communicated by a nerve. No one likes it though it does serve as a warning to do something about the pain source. Researchers at the University of Leeds have found a previously unknown mechanism through which pain is signaled by nerve cells. A discovery that could explain the current failings in the drug development process for painkillers and which may offer opportunities for a new approach. In order to control pain, one, must understand how it works. The research team, led by Dr Nikita Gamper of the University's Faculty of Biological Sciences, is investigating the difference between persistent pain, such as toothache, and pain that results from the increased sensitivity of nerves in injured or diseased tissue (for example when we touch inflamed skin), known as hyperalgesia. Hyperalgesia can be experienced in focal, discrete areas, or as a more diffuse, body-wide form. Conditioning studies have established that it is possible to experience a learned hyperalgesia of the latter, diffuse form. In research published online this week, in Proceedings of the National Academy of Sciences (PNAS), Dr Gamper's team has discovered that these two types of pain are generated by the same nerves, but result from different underlying mechanisms. The project, funded jointly by the Wellcome Trust and the Medical Research Council, investigated the painful effects of two substances that cause local inflammation: bradykinin and substance P. Both substances bind to specific receptors on nerve cells, generating signals to the central nervous system. Because the receptors are from the same family, it has always been presumed they stimulate the same signalling pathway. However, the team found that each receptor produces different signals; the one associated with bradykinin causing both hyperalgesia and persistent pain, whereas the one associated with substance P only caused hyperalgesia. "Dr Gamper says: "Pain originates from a series of electrical signals sent by nerve cells in to the central nervous system and ultimately the brain. Despite much progress, we still don't know enough about the mechanisms by which these pain signals are generated. However, this research has shown that whilst the sensation of pain can be similar between various conditions, the underlying molecular mechanisms may in fact be very different." Treatment approaches to long term pain include pharmacologic measures, such as analgesics, tricyclic antidepressants and anticonvulsants, interventional procedures, physical therapy, physical exercise, application of ice and/or heat, and psychological measures, such as biofeedback and cognitive behavioral therapy. Existing pharmacological painkillers are non-specific, designed to generally dull the reception of these signals in the central nervous system, and some stronger pain killers can provoke unwanted side effects such as disorientation, drowsiness or nausea. "What's exciting about these findings is that substance P may actually suppress the activation of the pain sensing nerves themselves," says Dr Gamper.