Often pain is from a tangible source, sometimes taking the form of a broken arm, angina, and even psychological distress following the loss of a family member. However, in some amputees, experiencing pain can often be confusing if it seemingly stems from a limb that ceases to exist.
This experience is called phantom limb syndrome, a condition in which patients experience sensations -both painful and non-painful- stemming from the absent limb and has been reported to occur in “80-100% of amputees”. In order to understand the mechanism behind phantom limb syndrome, the brain and its ability to change and adapt must be explored.
Brain plasticity, also known as neuroplasticity, describes the brain’s tendency to change due to new experiences. This plasticity refers to the ability for new neural connections throughout the brain to form as well as the changing of existing connections. It was originally thought that such changes in the brain were restricted to childhood, with the number of synaptic connections -gaps between neurons that allow for the transmission of chemical signals- in the brain, halving by adulthood. (Gopnik et al, 1999) This is due to a process called synaptic pruning, wherein rarely used neural connections are deleted and frequently used connections are strengthened; this allows for our brain to efficiently function as we age and learn new information.  Research support in the 60s of stroke patients recovering through physical therapy, however, suggested that brain plasticity can extend past infancy, as unaffected regions of the brain in stroke patients were found to have adapted to perform the functions of the affected regions. 
There are two types of plasticity: functional plasticity – the brain’s ability to transfer functions usually performed by damaged area(s) to undamaged areas and structural plasticity – the brain’s ability to physically change due to new experiences. 
During structural plasticity, new neural connections are formed and integrated into the central nervous system and through brain imaging techniques such as MRI and CT scans, the effect of stimuli on the neural pathways can be measured.
Ramachandran, a neuroscientist, hypothesised that structural plasticity occurs following amputation of the limb, leading to a mismatch between the sensation of the limb and the non-presence of it, a phantom limb. Sensory information is carried by the central nervous system from the limb to the primary somatosensory cortex, a part of the brain which receives and processes sensory information. When the limb is lost, so is the stimuli to the region of the somatosensory cortex involved in the sensations of the limb. However, in phantom limb syndrome, the cortex continues to receive sensory information from the absent limb- how does this occur?
Although the phenomenon is not fully understood, what Ramachandran suggested is that the amputation of the limb led to the reorganisation of the somatosensory cortex to compensate for the loss of stimuli, this meant that synaptic connections were re-wired, meaning that sensations felt by remaining limbs, in turn, invoked phantom sensations in the amputated limb.
This is illustrated in one of Ramachandran’s experiments, wherein stimuli, a cotton swab, was applied over random points on the amputee’s body and they were asked to report where they felt the sensation. Some reported having experienced the touch on their amputated limb, in addition to where the touch was applied, suggesting that structural plasticity had occurred. This was then confirmed in a subsequent MEG study – a neuroimaging technique for mapping brain activity – of a below the elbow amputee. When comparing the recording of both hemispheres, it was found that pathways had been reorganised in the left hemisphere to the point where the area that had received sensory information from the pre-amputated limb was no longer visible, and instead, sensations could be activated through “touch on the areas of the face and the arm above the line of amputation.”
Contributions from Ramachandran and modern research into neural mechanisms have facilitated the introduction of treatment approaches, such as spinal cord stimulation, acupuncture, and hypnosis. Despite this, there is a lack of reliable evidence on the effectiveness of these treatments for phantom limb syndrome.
One prominent treatment is mirror therapy: developed by Ramachandran, this form of therapy uses a mirror box to provide a reflection of the intact limb that allows the patient to create the sensation of moving the identical phantom limb. This is done through mirror neurons, which allow for the recognition of touch and feel in the phantom limb; when the patient wants to flex the intact limb, a signal is sent to the limb through the motor neuron. As this occurs, a copy of the signal is sent to the somatosensory cortex through those mirror neurons, allowing for the patient to feel their ‘phantom limb’ flex too. The benefit of this is that phantom limb syndrome causes uncontrollable sensations in their phantom limbs, such as clenching, which can be painful; through persistent use of the mirror box, however, the phantom limb can be trained, restoring control back to the patient. Supported by its “simple and inexpensive” nature, mirror therapy is seen as a viable option for PLS sufferers. 
In spite of the promise brought by mirror therapy, more research is needed to further support its effectiveness compared to other forms of treatment, however, neuroscientists hope that future studies will uncoil mysteries of the brain and with it, the phenomenon of phantom limb syndrome.
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