Body's natural painkillers may damp down phobias
The way humans are conditioned by fearful stimuli is to some extent damped down by the body's own pain-relief system, a study suggests. The finding may shine light on the neural mechanisms behind anxieties, phobias and even post-traumatic stress disorder.
Scientists have known for a long time that if you pair an innocuous stimulus (such as a tone) with something aversive (such as a shock to the feet), animals, including humans, will learn to show a "conditioned fear" response.
With repetition, the innocuous stimulus alone brings on the fear response. Both the learning and the initiation of this response take place in a part of the brain known as the amygdala.
One of the more perplexing features of the conditioned fear response is that, when the dreaded stimulus is something painful, people actually tend to experience less pain the more they are exposed to it.
Work in rodents has revealed that this is because opioids – chemicals that have a morphine-like effect on the body – are called into operation during the conditioning and they end up blunting the pain. Blocking the opioids not only stops the pain from being lessened, but also intensifies the learning process.
Falk Eippert at the University Medical Centre of Hamburg-Eppendorf, Germany, and his colleagues wanted to know if something similar operated in humans.
Thirty male volunteers were asked to watch green triangles and blue pentagons on a screen inside an MRI scanner. One of the symbols was followed half the time by a moderately painful application of heat to the forearm; the other was never followed by pain.
Half the volunteers were infused with naloxone, a drug that blocks the effects of opioids, while the others got saline solution as a control. The researchers were blind as to which group was getting what treatment.
The brain scans showed that in people whose opioid systems had been blocked, the amygdala showed a fear response that did not diminish with exposure. Every time they saw the symbol associated with pain, their amygdalas reacted strongly. In the control group, however, the activation decreased over the course of the experiment.
Because the group receiving naloxone was reacting more fearfully, the researchers speculate, they were learning the association more intensively.
The team also found behavioural evidence that this might be the case. At the beginning of each trial, volunteers had to perform a reaction time task – pressing a button to indicate on which half of the screen the symbol had appeared.
Overall, subjects reacted more quickly to the cue signalling pain than the cue signalling nothing – but the opioid-free subjects reacted significantly faster.
"This natural response advantage to something dangerous was much stronger in the people who received naloxone," says Eippert.
The researchers speculate that opioid deficiency could be a contributing factor to anxiety disorders and exaggerated fear responses. Knock-out mice whose opioid systems have been genetically "switched off" do seem to be prone to anxieties and exaggerated conditioned fear responses, points out Eippert.
"It potentially has far reaching implications," says Jon-Kar Zubieta at the University of Michigan in Ann Arbor, US. There is tremendous variability in how individuals respond to threats and stress, he says, which is thought to relate to the risk developing anxiety disorders.
"This study examines the circuits and neurochemical systems that are likely to underlie that response heterogeneity." The research could help open new avenues for understanding, preventing and treating these types of illnesses, he says.
Journal reference: Journal of Neuroscience (DOI: 10.1523/jneurosci.5336-07.2008)