Deliberately inflicting carefully controlled painful stimuli on human volunteers and seeing how well specific drugs reduce the feeling of pain can be an effective way of testing new drugs. So conclude two researchers who reviewed the available literature on these types of tests in a paper published in the British Journal of Pharmacology.
Pain is important. It acts as an alarm mechanism, warning us that something is about to cause physical damage. It could be triggered by something physical like a cut or bruise, or a temperature driven stimulus such as extreme heat or cold. It could be caused internally by injuries where nerves get trapped. Pain can also become a long-term sensation that lasts long after the damage has occurred. In this case it is referred to as 'chronic' pain, and this can be particularly hard to treat.
The need to tackle pain is huge. A fifth of Europeans suffer from daily pain requiring treatment, with the proportion increasing in people over 70 years old. But pain control is still often insufficient or unsatisfactory because the available drugs fail to provide adequate relief or produce major side effects. Pain has therefore remained one of the major healthcare problems generating estimated socio-economic costs of $560-635 billion/year in the USA alone.
Finding new drugs is complicated because you can't measure pain directly. In animal models you have to watch animals as they respond to stimuli, and in human trials you have to get individuals to report how they feel. On top of this, the body has a number of different ways of detecting pain- generating stimuli, and each mechanism is likely to respond to a different set of pain-killing drugs.
Based in Frankfurt am Main, Germany, Bruno Georg Oertel and Jörn Lötsch started out with a theory. "We thought that if a pain-relieving drug was effective in a particular experimental pain model and also in a specific type of clinical pain, then the experimental model should be predictive for the particular clinical setting," says Lötsch, who works in the Institute of Clinical Pharmacology at the Goethe-University.
They found that overall, human experimental pain models were able to predict how well a drug worked in patients better than previously realised. "Not using these pain models in drug development seems to be unjustified – in fact they should be used routinely in drug development programmes," says Oertel, who works in the Fraunhofer Project Group for Translational Medicine and Pharmacology (TMP), an initiative supported by the Hessian Excellence Initiative ("LOEWE") that runs at the junction between pharmacological research in academia and in the pharmaceutical industry.
The process isn't simple though as not every model can predict every clinical setting. "However, by analysing the way that drugs work in experimental and clinical settings, we identified that different sets of experimental pain models, rather than single models, may be best suited to provide cost-effective yet predictive studies in analgesic drug development," says Lötsch.
"It is difficult and unusual to undertake truly translational research in pharmacology. Here, Jörn Lötsch and Bruno G. Oertel have focused on experiments on humans to bridge the gap between animal research and clinical pharmacology. The review examines how well clinical analgesia is predicted by human experimental pain models, with a view to guiding model selection in phase I studies. The authors identify important disparities between drug effects on experimental and clinical pain. This will help inform thinking on the refinement of human and animal models of pain, ultimately helping the pharmaceutical industry bridge the translational gap in the pain field," says Editor-in-Chief of the British Journal of Pharmacology, Professor Ian McGrath.
More work is needed before this approach is fully ready to use, but the researchers believe this could lead to a more cost effective approach that can help scientists gain valuable information about the ways new drugs are working.
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
From Dr Strangelove and water fluoridisation to climate change, scientific method and facts are not always enough to win over the sceptics
On a blog post at PLOS, the tropical disease expert Peter Hotez and postdoctoral fellow Jennifer Herricks take a run through the data on the biggest killers of children around the world in 2013, part of a new dataset from Global Burden of Disease study published in the January Lancet.
Tory MP David Tredinnick seems to believe that astrology could inform and improve UK healthcare. This view is misguided and potentially dangerous
Resistance to vital antimalarial drugs called artemisinins has spread across Burma to the Indian border. If not contained, it could ultimately hit Africa hard
Clostridium difficile sickens nearly half a million Americans annually, killing about 29,000, say federal health officials. They warn hospitals and nursing homes to tighten hygiene protocols.
Study looking at transmission among men who have sex with men recruited 545 participants at high risk of contracting HIV A daily pill can effectively protect gay men against infection with HIV
An experimental therapeutic vaccine from Danish drugmaker Bavarian Nordic helped significantly extend survival in patients with advanced prostate cancer, according to results of a small early-stage trial conducted by the U.S. National Cancer Institute.
Scientists interviewed more than 1,000 men, women and children who were forced into sex work and hard labor. The result is the largest study to detail the health of human trafficking survivors.
Gerbils from Asia rather than black rats were responsible for repeated outbreaks of the bubonic plague in Europe, a study suggests.
The so-called "cuddle-chemical" seems to block the action of alcohol in the brain, preventing the tell-tale signs of drunkenness in rats