People who have had a limb amputated often have the vivid and strange experience of feeling as if the amputated limb is still with them or even moving. Many people are also simultaneously afflicted with unbearable pain from these sensory apparitions. This is called phantom limb. Alleviating pain of known cause, such as that caused by inflammation and tumors, is difficult enough. It is even more difficult to treat the pain in these non-existent limbs. However, there is a technique that is very effective. It is the use of mirrors to create the illusion that the amputated limb is still on the body. Until recently, no one knew how this works. But Hertaforo of the University of Heidelberg in Germany thinks she may have cracked the mystery. As she recently explained to an audience at the European Neuroscience Forum in Vienna, if she’s right, she may have opened the door to treating other forms of persistent pain. It’s all in the mind Dr. Faurot and her colleagues studied a phantom limb called the “stretching illusion. After a hand was amputated from the wrist, some patients felt that the amputated hand was extending from the site of the amputation (extensor hallucination), while others felt it was extending from the elbow (incomplete retraction hallucination) or shoulder (complete retraction hallucination). The researchers wanted to know what caused these hallucinations, so they asked patients to imagine opening and clenching their lost fists, while using magnetic resonance imaging (MRI) to observe the patients’ brain activity during this time. Patients with extended hallucinations showed activity in the motor cortex, the area of the brain that controls hand movements. This is consistent with the activity of the cerebral cortex in able-bodied individuals performing this movement. In contrast, those patients who suffered from incomplete and complete retraction had different responses. They showed activity in the motor cortex of the brain that controls the elbow and shoulder, respectively. In other words, the greater the retraction, the more pronounced the reorganization of the internal neural networks of the brain involved, and the more severe the pain. This correlation led Dr. Faureau to wonder if the principle of pain reduction by mirror therapy was to reverse the neurological changes caused by the “retraction”. In mirror therapy, a patient who has had one hand amputated has the normal hand and the phantom hand placed on opposite sides of a mirror. The mirror image of the normal hand is repositioned and projected in the position where the patient perceives the hallucinated hand to be. The patient was then asked to move both hands (normal and hallucinated) simultaneously and to watch their movements. The illusion created by the mirror made the patient feel that his two hands were indeed moving. After a few weeks of this 15-minute daily treatment, about half of the patients reported that their affected limbs and their accompanying pain had disappeared. Dr. Faurot and her colleagues again turned to magnetic resonance technology to record the brain activity of amputee patients during the mirror image treatment in order to clarify the principle. As expected, patients without phantom limb pain showed activity in the motor cortex, which controls the hand. They also showed activity in the sensory cortex that controls the hand, the part of the brain that receives signals from the hand. The visual feedback signal provided by the mirror was interpreted by the sensory cortex as the real hand. People who felt pain had no such visual feedback system and were not active in either sensory or motor cortex. Dr. Faurot speculates that mirror therapy may be able to restore feedback function in patients with retracted affected limbs by providing enough neural information to the brain to reverse the changes that come with amputation. The team is now conducting follow-up experiments to confirm this hypothesis. These results suggest that Dr. Faureau would do well to understand the affected limb as unconscious learning, just as motor reflexes and perceptual skills are. Based on this interpretation, the principle of the mirror experiment should be to replace the harmful memory with the harmless one. Based on this hypothesis, she conceived that another treatment route should be to prevent the formation of memories about pain in the first place. To test this idea, she had patients who underwent amputation take a drug called memantine. The drug blocks the activity of a protein molecule called the NMDA receptor, which plays an important role in many forms of memory and learning processes. Thirteen patients took memantine for four weeks after their amputation (and in some cases, before their amputation as well). The researchers then continuously observed these patients’ brain activity and limb sensation over the course of a year, and compared their findings to those of a group of patients taking placebo. To their relief, they found that memantine not only reduced the changes in the brain, but also reduced the number and intensity of pain in the affected limb. Taking it a step further, Dr. Foro wanted to see if her theory of pain memory could be applied to treat other chronic pain. She turned to a condition called myofibromyalgia, which is characterized by pain that spreads throughout the body. With the help of MRI technology, she found a network of abnormal memory traces in the brains of patients suffering from this condition. Many parts of their brains were transitionally active, not only in areas involved in limb sensation and movement, but also in areas involved in the perception and processing of pain signals. The researchers also found that memantine was able to reduce pain by inhibiting activity in the infested parts of the brain. Encouraged by this result, they are now trying to eliminate pain memory with drugs that activate the cannabinoid receptor system in the brain. Previous studies have pointed to the involvement of these receptors in the elimination of unpleasant memories, such as memories of fear. Dr. Floro hopes that pain memories, which are a type of unpleasant memory, will be similarly eliminated. She has also tried non-pharmacological treatments. For example, the team uses cognitive behavioral therapy with patients with myofibromyalgia to get them to stop reacting to pain and focus on something pleasant. Dr. Faurot believes that if reinforcement loops are eliminated and so-called memory incompatible with pain is introduced, the memory traces of pain in the brain will be reduced or even disappear. If Dr. Foro’s memory hypothesis is correct, then a revolutionary way of treating chronic pain will be on the horizon. This would undoubtedly be a boon to the millions of patients who suffer from such pain. After all, pain comes from the mind. In fact, pain itself is a hallucination, a ghost in the brain. So the brain may be a good place to start eliminating this ghostly, torturous sensation.