Drug researchers appear to have got it wrong in the search for pain-relief compounds to address the sustained pain that follows an injury.
A Harvard Medical School study suggests that researchers and pharmaceutical drug testing programs – when assessing the efficacy of experimental compounds – have been targeting the wrong kind of pain response in test subjects.
This means that potentially helpful pain drugs have probably been abandoned during the testing phase.
Why it matters
This is especially troubling in light of the research scramble to find alternatives to grindingly addictive opioids, which don’t work that well to combat chronic pain in any case.
It all comes down to a poor understanding of a simple, everyday set of events.
When you pull your hand away from a thorn-laden bush or a too-hot cooking pot, you tend to immediately assuage the pain by squeezing or sucking the injured finger. The two actions seem to be part of a single evolutionary reflex.
Different kinds of ‘ouch’
But the Harvard researchers found they are not.
It was already understood these response mechanisms occur in different regions of the brain. But experiments with mice show they are triggered by different neural pathways – all the way from the spinal cord to the fingertips – and have a different molecular foundation.
The reflexive response of pulling your hand is the evolutionary strategy for escaping from physical harm – and seems to contain its own variety of pain. Think of the initial sting or burn.
Soothing the pain by licking, sucking or squeezing your finger is a distinctly separate evolutionary response designed to cope with the ongoing pain of the injury. Think of the throb that takes over.
The researchers say most current methods of testing pain-drug efficacy rely on measuring the initial sting, when they should be assessing the ongoing throb.
As a result, they said in an article in the Harvard Gazette, some drug compounds that might have been successful in assuaging the sustained pain – the lasting sensation of pain that immediately follows injury – could have been dismissed as ineffective because they were assessed against the wrong outcome.
“All these years, researchers may have been measuring the wrong response,” said study senior author Qiufu Ma, professor of neurobiology in the Blavatnik Institute at Harvard Medical School and a researcher at Dana-Farber Cancer Institute.
“Indeed,” Professor Ma added, “our results could explain, at least in part, the poor translation of candidate treatments from pre-clinical studies into effective pain therapies”.
More tailored approach needed
He said the ongoing opioid crisis has created an acute and pressing need to develop new pain treatments, and that his study findings suggest “a more tailored approach to assessing pain response would be to focus on sustained pain response rather than reflexive protective withdrawal”.
Clinical observations of patients with neurological damage, together with past research, have outlined the distinct brain regions that differentiate between the reflexive withdrawal from a skin prick, for example, and the long-lasting pain arising from tissue injury caused by the pinprick.
The new study, published in Nature, is the first one to map out how these responses arise outside the brain.