After an injury or pain-inducing experience, the body often heals itself, but a chronic pain may continue even after healing. National Institute of Medicine surveys suggest that some 116 million American adults are in chronic pain. Chronic pain is often accompanied by such emotions as anxiety, depression, and a significant reduction in quality of life. Drugs like opiates, steroids, and non-steroidal anti-inflammatories can be very effective in reducing acute pain, but may have little or no effect when post-healing chronic pain sets in.
How can pain persist when the original cause is gone? Clues have emerged from brain scans of chronic pain patients that show no sign of augmented activity in pain-mediated areas but do show increased activity in emotional and motivational areas of brain. The thought has now emerged in several research labs that chronic pain may actually be a memory. As if the chronic pain itself is not bad enough, the pain learning process may induce degenerative changes in emotional circuitry.
The idea dates back to the work of Pavlov over 100 years ago revealing that animals experiencing painful stimuli learn to associate that pain with other ongoing events, called conditioning stimuli, which include the associated emotional distress. The animals remember both the pain and the negative emotion, even when neither is any longer present. But until the last few years, nobody seems to have applied these findings to the issue of chronic pain in humans.
The idea is that a prolonged period of acute pain strengthens the emotional pathways that are activated during pain, and continuously reinforces the signals so that they do not go away even after the physical pain is gone. This process might even be thought of as a kind of addiction. Many theorists believe that the usual addictions, as to opiates, nicotine, etc. have a large learning and memory component.
We have known for a long time that pain can induce huge emotional distress. Numerous anecdotes establish that unpleasant emotional states are magnified by pain. But we also know that thoughts and emotions can regulate pain. For example, a mother's kiss may reduce a child's pain from a sudden injury better than any analgesic. In the heat of combat, a wounded soldier may feel no pain until after the attack is over. These pain-suppressing effects are not just psychological but even include inhibition of pain signals as they arise in the spinal cord.
Notably, one of the key brain areas involved in pain is the hippocampus, which is crucially involved in forming memories. But the hippocampus is a key linchpin in the neural circuitry that processes emotions and mediates stress.
You might think that this is a perverse feature of nature. But actually the process has its uses. Pain provides a teaching signal that makes one want to avoid such situations in the future. But in chronic pain the lesson becomes so well entrenched that the pain memory cannot be extinguished.
If this theory is correct, it means that the usual treatments for chronic pain need to focus on memory mechanisms. Minimizing the pain while healing is in progress should reduce the likelihood of developing chronic pain memories.
But of course, prevention is not always easy to accomplish. Today, physicians are more aware of the addictiveness of the most reliable pain killers: opiates. They tend to cut short use of opiates in order to prevent drug addiction.
One possible treatment may be akin to emerging treatments for post-traumatic stress syndrome (PTSD). Development of PTSD is reduced if morphine is given immediately after an acute trauma. A beta-blocking drug, propranolol, can have a similar preventing effect, presumably because it blocks memory reconsolidation. Whenever you recall a memory, it will be re-stored. While it is consciously "on-line," the memory is vulnerable to modification, and a new and perhaps less traumatic version of the memory can be saved in memory. In PTSD therapy, you might recall the memory and have its reconsolidation blocked by certain drugs that prevent memory consolidation.
Another possibility is to target the synaptic biochemistry involved in pain. Neuronal NMDA receptor molecules are involved in the emotional component of acute pain, and one drug that acts on these receptors, D-cycloserine, has been shown in animal studies to inhibit pain-related behavior for weeks afterward. There is also a protein kinase enzyme that mediates the emotional distress of pain. Animal studies show that there is a peptide that inhibits this enzyme and in the process reduces pain-related behavior. Work is underway in several laboratories trying to identify appropriate molecular targets in chronic-pain pathways so that appropriate drug therapies can be developed.
Sources:
Apkarian, A. V., Baliki, M. N., and Geha, P. Y. (2009). Towards a theory of chronic pain. Prog. Neurobiology. 87, 81-97.
Mansour, A. R. et al. (2014). Chronic pain: the role of learning and brain plasticity. Restorative Neurology and Neuroscience. 32, 129-139.
Melazck, R., and Wall, P.D. (1965). Pain mechanisms: a new theory. Science. 150, 971-979.
Sandkühler, J., and Lee, J. (2013). How to erase memory traces of pain and fear. Trends in Neurosciences. 36(6), 343-352.
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