Anatomy of pain can bring relief
Researchers are tracking down how emotional inputs modify our experience of pain, writes Stephen Pincock
TOM had been in pain for close to a decade by the time he walked into Professor Michael Nicholas’s office last year. What began as a high school cricket injury — a stress fracture in his lower back — had led to niggling back pain that gradually worsened until he was often in agony, only able to sit for a few minutes at a time and unable to walk further than 100 metres.
Tom was forced to quit full-time work, started relying on a back brace and was ‘‘ popping as many painkillers as I could’’ — all to no avail.
Surgeons, osteopaths, GPs and acupuncturists all told him much the same thing: the original injury had healed, so what was the problem?
‘‘ They would all look at me and say ‘ There’s nothing wrong with you’,’’ recalls Tom, who asked to withhold his full name.
That changed when a surgeon referred Tom, now in his early 30s, to the Pain Management and Research Centre at Sydney’s Royal North Shore Hospital. There, Professor Nicholas prescribed a combination of physical rehabilitation and psychological therapy. Tom began to see immediate benefits. ‘‘ Over the past 12 months or so, I’ve really been able to learn to control my pain,’’ he says. ‘‘ The most important part of that is controlling the psychological side of things.’’
An estimated one in five Australians suffers persistent pain, defined as pain that continues for more than three months. Precisely why it persists, sometimes without any obvious physical cause, has remained something of a mystery.
Now, Queensland researchers have made a discovery that sheds important new light on how the brain processes pain, and how central emotions are in the pain experience. Their work might lead to new treatments for chronic pain conditions.
Andrew Delaney and his colleagues at the Queensland Brain Institute have published a study in the journal Neuron about the intricate pathways that are traced in the brain during the sensation of pain (2007;56:880-892).
Using a dye to label neurons in rat brains, they were able to follow connections between the brain’s ‘‘ pain relay station’’, known as the parabrachial nucleus, and another brain region known as the amygdala.
They found that nerve fibres from the pain relay station ran to specific cells in the central part of the amygdala, forming what scientists call a ‘‘ high fidelity connection’’.
‘‘ That means that every time a neuron in the parabrachial nucleus experiences a pain input, the signal is sent to the central amygdala. The high fidelity connection practically ensures the central amygdala neuron fires as well,’’ Delaney explains.
This very reliable connection means that any signal that reaches the brain’s pain centre is almost guaranteed to set off a signal in the central amygdala. And the cells there trigger emotional responses — emotions, hormones, blood pressure increases and so on.
From a clinical perspective, these findings make a great deal of sense, says Professor Nicholas.
‘‘ Since the mid-1960s, we in the pain fraternity have seen pain as not simply a sensation, which is probably how most of the community thinks of pain, but as being defined by both a sensory and a emotional experience,’’ he says.
‘‘ What travels through the nerves when you get an injury is not pain, it is activity in nerves,’’ he explains.
‘‘ We call that ‘ nociception’. It’s only when it gets to the brain, and the brain synthesises it and incorporates a number of other inputs, that it becomes an experience of pain.’’
This is why people with chronic pain do so much better when they use psychological strategies to help manage their pain responses, Nicholas says. And understanding the neurological links between pain and emotion is likely to help clarify just how the chronic pain develops in the first place.
Professor MacDonald Christie, director of basic research at the Pain Management Research Institute at the University of Sydney, says in the past five or six years it’s ‘‘ become increasingly clear that the transmission of pain signals from the spinal cord up through the parabrachial nucleus and into emotional control systems is a very important component of pain’’.
‘‘ The changes that occur in that system in persistent pain states are terribly important for the establishment of those states,’’ Christie says.
Delaney agrees. ‘‘ It could be that people who experience chronic pain develop problems because they have dysregulation of the processing in the amygdala, and of the pain input into the amygdala,’’ he says.
This is particularly likely because the part of the amygdala the Queensland group studied also sends messages directly into the brain systems that feed back to the spinal cord and control pain sensations.
Christie says this means that aberrations in the way the amygdala functions over time in chronic pain patients ‘‘ will not only affect their anxiety states, but also affect their actual sensation of pain and contribute to the establishment of the chronic pain state’’.
Further, the Queensland researchers also uncovered a means by which the strong connection between the pain and emotion centres in the brain can be interrupted.
They showed that a brain chemical called noradrenaline, which is released in situations of stress or when we need to be on high alert, regulates the link.
‘‘ This seems to indicate that during times of stress, our emotional response to pain may also be modulated, perhaps reducing the emotional impact of a painful experience,’’ Delaney says.
Nicholas says this is apparent at times of high excitement or stress, when people can sometimes remain unaware they are injured at all, for a time.
‘‘ You can see that in footballers when they come off the ground and discover they’ve got a broken nose they didn’t notice during the game,’’ says Nicholas.
‘‘ If you saw that footballer in the street and punched him in the nose, he’d certainly recognise it as pain.’’
For pain researchers, understanding the role of noradrenaline helps explain why some of the drugs currently used to treat pain actually work.
One example is the class of antidepressant drugs known as noradrenaline-reuptake inhibitors, such as reboxetine.
‘‘ They allow noradrenaline to stay longer outside cells to do its job,’’ Delaney says. ‘‘ By allowing noradrenaline to hang out a little longer, maybe you down-regulate that response through your parabrachial to the central amygdala.’’
The findings could treatments.
‘‘ The new evidence we’ve got in this paper is that this is potentially one of those synapses where we may be able to use pharmacological therapy to target this part of pain,’’ says Delaney.
Although such new drugs could be years away, recent history suggests the basic science conducted in Brisbane has a good chance of translating into therapy.
‘‘ There’s already good recent history of this sort of research translating very quickly into very useful therapies,’’ Delaney says.
‘‘ So we’d hope that not too far down the track we might have something that would allow us to target the cells that receive these pain inputs, or maybe target the terminals that release the noradrenaline to allow them to be upregulated.’’
For people like Tom and the many thousands of others with chronic pain, that would be welcome news indeed.
Channels of discovery: Andrew Delaney’s research shows intricate pathways are traced in the brain during an experience of pain