Phantom limb pain has intrigued scientists since before neuroscience was considered a field of study. First clinically described by Ambroise Paré in 1551, the term “phantom limb” wasn’t coined until the Civil War by surgeon Silas Weir Mitchell. Around 80 percent of those who experience limb loss feel phantom limb pain (PLP) at some point, and 85 percent report the pain lasting longer than two years (Darnall, 2010).
PLP comes about from the missing peripheral nerves in the amputated limb. According to Mayo Clinic, when the brain no longer receives input signals from the missing limb it tries to send outputs to the residual nerve endings. Since these residual nerves have no receptors the signals get mixed, and the spinal cord, which is missing the peripheral input, sends a message to tell the brain that something is wrong. This message is often one of pain.
Many different treatments have been developed to treat PLP, although most are not effective in the long term. Along with painkillers, anesthesia has been used. However, the continuous blocking of nociceptive fibers and electrical activity in the general region around the amputated limb resulted in too many complications for patients (Makin, 2021)
Recently, PLP in amputees has been treated through mirror box therapy when painkillers prove to be ineffective. In 1996, neuroscientist V.S. Ramachandran set up a simple experiment to see if illusions could trick the visual system, and in turn, the brain. It works by attempting to normalize the representation of the missing hand in the somatosensory and motor cortex. Mirror Box Therapy (MBT) attempts to trick the brain into thinking the amputated limb is still existent and can be moved. Over time the brain will recognize that moving the limb in the mirror does not cause pain, which will prevent a painful reaction when the brain sends signals to the missing limb. However, according to Amputee Coalition, in a study of 40 amputees, pain was reduced by an average of around 40 percent. MBT is a brief relief from phantom limb pain which can help reduce painkiller usage. However, it does not target the underlying physiological cause and only induces minor changes to the brain.
One of the newest treatments of PLP is Targeted Muscle Reinnervation (TMR). Residual nerves from the patient’s amputated limb are primed to regenerate and innervate nearby muscle cells. The process deals with correcting anomalous nerve endings and their disruptive electrical signals. Those who undergo this process were found to have experienced a decrease in PLP whereas those who did not saw a slight increase over one and a half years. (Dumanian et. al., 2019) TMR effectively reassigns unused nerves. Unlike anesthesia, no function is lost because the peripheral nerves are reinnervated instead of eliminated. TMR not only corrects the denervated muscle fibers that cause PLP, but it also changes the brain's physiology. A study of amputees who have undergone TMR tested the functional connectivity and different levels of organization in the primary motor cortex (M1) and the somatosensory cortex (S1). In comparison to control amputee patients, S1 maps of those with TMR were similar to the brain organization of non-amputees. M1 regions were also similar to non-amputee brain structure when those in the control group showed a reduction in their upper limb maps. Although connectivity was reduced in the TMR patients, the brain was still able to reorganize itself to fight dysfunctional cortical plasticity and reorganization after an amputation. (Serino et. al., 2017)
While TMR and MBT both have the goal to “amputate” phantom limbs, they target different systems. MBT focuses on the visual system in an attempt to tell the brain to stop sending pain signals. TMR could potentially become the preferred method of treatment because of its targeting of the physiological causes of PLP without harming the surrounding nerves as well as its ability to utilize the brain’s plasticity to benefit the patient.
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Sources
Andrea Serino, Michel Akselrod, Roy Salomon, Roberto Martuzzi, Maria Laura Blefari, Elisa Canzoneri, Giulio Rognini, Wietske van der Zwaag, Maria Iakova, François Luthi, Amedeo Amoresano, Todd Kuiken, Olaf Blanke, Upper limb cortical maps in amputees with targeted muscle and sensory reinnervation, Brain, Volume 140, Issue 11, November 2017, Pages 2993–3011, https://doi.org/10.1093/brain/awx242
Darnall, B. D. (2019, February 28). Mirror Therapy. Amputee Coalition. https://www.amputee-coalition.org/resources/mirror-therapy/
Dumanian, G. A., Potter, B. K., Mioton, L. M., Ko, J. H., Cheesborough, J. E., Souza, J. M., Ertl, W. J., Tintle, S. M., Nanos, G. P., Valerio, I. L., Kuiken, T. A., Apkarian, A. V., Porter, K., & Jordan, S. W. (2019). Targeted Muscle Reinnervation Treats Neuroma and Phantom Pain in Major Limb Amputees. Annals of Surgery, 270(2), 238–246. https://doi.org/10.1097/sla.0000000000003088
Tamar R Makin, Phantom limb pain: thinking outside the (mirror) box, Brain, Volume 144, Issue 7, July 2021, Pages 1929–1932, https://doi.org/10.1093/brain/awab139
Perry, E. (2021, September 24). Targeted Muscle Reinnervation | Johns Hopkins Department of Plastic & Reconstructive Surgery. https://www.hopkinsmedicine.org/plastic_reconstructive_surgery/services-appts/tmr.html
Phantom pain - Symptoms and causes. (2021, June 11). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/phantom-pain/symptoms-causes/syc-20376272
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