New Theory of Phantom Pain Could Mean End for Illusory Treatments

Research has contradicted longstanding theory around the origins of phantom limb pain (PLP), where amputees feel agony in limbs that have been amputated, persisting even decades after the removal. The research suggests that new interpretations of PLP are required to develop effective treatments. 

Up to 79% of amputees suffer from phantom limb pain and it represents a major obstacle in improving their quality of life. Technology Networks recently heard a talk from the UCL Institute of Cognitive Neuroscience’s Dr Tamar Makin, whose research examines how brain reorganizes itself after the loss of a hand. Her findings have offered fascinating new insights into how our plastic brain functions and could point to new treatments regimes for phantom limb pain.

Makin explained that the current accepted theory of PLP involves error signals coming from the region of the brain responsible for processing touch and feeling, the somatosensory cortex. This area of the brain contains a “map” of the rest of the body, where different sections of cortex are linked to the corresponding body area.When a limb is lost, said Makin, theory suggests that a process of reorganization occurs.

With the limb no longer present, the area in the somatosensory cortex corresponding to that limb is deprived of input. Nearby cortex areas then “invade” the limb’s brain map, meaning that an error signal is created between what the brain expects from that limb’s area and what is felt – resulting in phantom pain.

Mirror box treatment – not just a TV magic trick

Makin showed a clip from the popular US TV series House, where a dashing but damaged doctor takes maverick approaches to cure mystery conditions.

In the clip, a particularly resistant phantom pain patient has been abducted by the titular Dr House, and is subjected to a “mirror box” treatment, where they are forced to observe a reflection of their missing hand, designed to trick their brain into thinking it has reappeared. Hugh Laurie’s House then asks the patient to release the tension in their hand, and, miraculously, their pain disappears.

After playing this outlandish clip, Makin pointed out that such mirror box treatment (minus the forced abduction) is actually the standard clinical approach for phantom pain, based on the “reorganization” theory outlined above. Even modern therapy updates use techniques like virtual reality to obtain the same illusory effect.

In, this clip, Dr House (Hugh Laurie) tries an innovative kidnapping-based method to treat a patient's phantom pain. Credit:House M.D. via YouTube

Thirty years on, a missing hand mapped out in the brain

But the evidence to back up mirror box treatment is itself a trick of the mind, said Makin. She pointed out that the theoretical base for the treatment comes from animal studies, and that more recent human studies have failed to show clinical efficacy. Her lab decided to take a closer look at what was happening in the brains of amputees when they experience PLP.

Makin presented data from her lab, which showed a cortical hand map taken from a patient who had been an amputee for over thirty years. The patient’s intact hand showed clear cortical maps of clusters of neurons responsible for each individual finger. Surprisingly, Makin’s team found that the maps remained intact in the patient’s missing hand, without any sign of the reorganization that might have been expected.

A further study looked at a group of 17 amputees, who had been living without a hand for on average 18 years. The cortical maps in this group were similarly preserved in the missing hand, down to a level of detail that showed that brain activation representing the pinky fingers was more closely related to the adjacent ring finger than to the thumb. A comparison group of people born without a hand showed that these maps were only present in the amputees.

In complete opposition to what would be expected if hand maps were disrupted and reorganized, Makin said that in both studies, “people that experienced more chronic phantom pain actually show higher levels of activity in the missing hand cortex when they're moving their phantom hand.”

New approaches needed to help patients

How do these findings translate into meaningful benefit for patients? Makin’s lab treated a group of patients with PLP, who were asked to move their missing limb whilst receiving either non-invasive brain stimulation or a sham procedure. Patients who received the brain stimulation felt immediate relief from pain that persisted for up to a week after the stimulation. Crucially, the patients who felt the most significant benefits saw the greatest reduction in brain activity in the hand cortex.

Makin’s team noted that these reductions were paired with increases in brain activity in regions of the pain network, which includes brain regions like the insula and secondary somatosensory cortex. Makin posited that it was changes in these areas that were actually driving the clinical benefit patients experienced, rather than signals from the hand cortex.

Makin’s work suggests that for patients suffering from PLP, new approaches may be required to achieve long-term relief for a condition that has baffled neuroscience for decades.

Speaking to Technology Networks, Makin gave her thoughts on the direction of future research in this area. “We need to think outside the box (mirror box in this specific case) and try to consider alternative mechanisms and treatments for PLP. Currently the vast majority of research is devoted to the mirror box and its (fancier) derivatives, e.g. virtual reality. If, as this new evidence suggests, the sensorimotor cortex is not actively contributing to PLP, then we should consider alternative treatments,” she commented [Updated February 11, 2020].

This article was updated February 11, 2020 to include additional quotes from Tamar Makin.