A short peptide isolated from human saliva has potentially powerful painkilling properties

Researchers in France have discovered a natural painkiller in humans which in tests on rats is several times more potent than morphine. The compound, a short peptide of five amino acids, has been named opiorphin. The researchers suggest it has potential therapeutic uses in reducing pain. 

Catherine Rougeot and colleagues at the Institut Pasteur in Paris isolated opiorphin from human saliva, having previously identified a similar potent pain inhibitor in rats. 

Laboratory studies demonstrated that opiorphin exerts its effect by inhibiting the activity of two enzymes, termed ectopeptidases, found on the outer membrane of nerve cells. In response to a painful stimulus, compounds called enkaphilins are released by the body as a counter-measure. However, these have a short half-life, of the order of seconds, and are rapidly catabolised by ectopeptidases. The researchers showed that opiorphin inhibits two of these enzymes, possibly by chelating zinc, which is necessary for the enzymes’ activity. This in turn increases the persistence of the pain-reducing enkaphalins. The team showed that opiorphin reduced pain in rats, with a greater potency than morphine. 

’We are now carrying out modelling studies on the molecule and looking at possible mimetics,’ Rougeot told Chemistry World. Her team is also looking at the pharmacological profile of the molecule relating to other potential effects on areas such as depression, memory and panic. 

Jack Morley, a consultant neuropharmacologist with the Pain Relief Foundation in the UK, said that the discovery of opiorphin represented ’a major advance that could lead to new understanding of the physiological significance of the enkephalins.’ He added, ’It is now over 30 years since the enkephalins were discovered. Since then, enkephalinergic pathways affecting pain and mood-related states have been postulated in natural neurotransmission, and in neurotransmission in response to external stimuli, but experiments to prove these postulates have led to confusion rather than enlightenment. Now the availability of opiorphin promises that many of these issues will be resolved.’ But the therapeutic implications of the discovery are much less certain, said Morley. ’It is likely that metabolically-stable, pharmacologically active forms of opiorphin can be synthesised, and these would be of potential use in the treatment of some types of pain, and emotional disturbances,’ he told Chemistry World. ’However, previous clinical trials with less specific enkephalinase inhibitors have been disappointing.’ 

Simon Hadlington