Scientists have used a technique called super-resolution microscopy to show for the first time how chemical triggers in the nervous system can amplify the pain experienced by mammals in response to certain stimuli.
The findings hold out hope that new therapies may be developed that effectively target pain in the area where it arises, rather than conventional painkillers that work on the brain.
The pain system employed by mammals probably evolved to alert them to life-threatening dangers.
As they approach objects that are extremely hot or cold, or are biting them, they experience intense pain, allowing them to get out of harm’s way.
But, in certain diseases, that defence mechanism malfunctions and rather than providing a short, sharp, shock – it produces long-term, chronic pain, seen with some illnesses affecting humans such as neuropathies, arthritic pain or migraines.
Researchers in the Faculty of Biological Sciences at England’s Leeds University, in collaboration with colleagues in the US and China, have discovered that, under certain conditions, the molecular sensors that respond to physical stimuli can be turbocharged – to intensify the electrical signals reaching the brain.
The brain interprets those signals as pain.
In animal studies using rat nerve cells, they found that the normal chemical messaging system used by the nerves to detect heat and involving calcium ions as “messengers” were supplemented by what is known as the calcium-activated chlorine channel. It is this combination that amplifies the electrical signal to the brain.
Their research findings have been published in the journal Science Signaling.
The research team used super-resolution microscopy to allow them to see in exceptional detail the interaction of the molecules involved in nerve signalling.
Professor of neuroscience Nikita Gamper, who supervised the research, says the findings show how environmental threats are detected and then processed by the nervous system.
“And of course, this understanding is also important for us to be able to combat the flip side of the sensation of pain – when people begin to experience pain that is no longer protective or beneficial, such as pain from inflammation, cancer and many other conditions.
“These are conditions that damage the quality of life experienced by many people.”
This pain amplification mechanism happens in the peripheral nervous system which feeds into – but is separate from – the central nervous system, made up of the spinal column and brain.
For Gamper, that division opens-up the possibility that drug therapies to reduce chronic pain could be targeted on the peripheral nervous system rather than the brain.
“The painkillers that we currently use act on the central nervous system and brain. Developing painkillers that work on brain function is very hard because the brain is a complex organ and although you might solve one problem, you often get unwanted side effects.
“Opioids are standard analgesics, but they are highly addictive. Therapies based on the peripheral nervous system would potentially have less effect on the brain.”
Although the study was conducted on nerve cells from rats and the applicability to the human nervous system is yet to be confirmed, there are reasons to believe that while there is a big difference between the human and rat brains, the peripheral nervous systems bear much closer similarity.