The Dark Side of Neuroplasticity

By Sreenidhi Venkatesh

It was believed for a long time that once the brain was fully developed and had laid its paths in a fully-grown adult, it was hard-wired and there was little possibility for change. This belief has been proven to be wrong numerous times over the past decade as neuroscientists grapple with the idea that the mammalian brain is malleable. In response to internal and external stimuli (positive or negative), the human brain possesses the ability to recognise changes and adapt and re-wire its circuits. Neuroplasticity has often been broadcast as an incredible concept where one can build brain power by picking up new skills like learning a new language or playing an instrument, or re-training the brain to conduct normal speech and movement while recovering from an injury or stroke (Shaffer, 2016). However, during the process of re-organisation and developing new patterns, the brain has the ability to maladapt which leads to unintended pathophysiological effects (Lozano, 2011).

One of the main facets of the dark side of neuroplasticity is in relation to the way the brain processes pain. Pain is an essential stimulus we experience as humans as it lays a foundation for our ability to learn from and not repeat an act that produces a noxious stimulus. It is a defence mechanism that we have developed with evolution in order to alert our brain that it is in danger’s way and must remove itself from the situation to prevent any further harm (Apkarian, Baliki & Geha, 2009). The pain pathway elicits a response from extensive regions of the brain which include the limbic system also known as the paleomammalian cortex and somatosensory projections. The pain pathway is composed of: transduction of the noxious stimulus into an electrical message, to being transmitted along neuronal pathways, to being modulated in the brain after which the sensation can be felt (Yam et al., 2018). While this is a traditional pain pathway, the brain can modify these pathways to unintentionally trigger pain, an example of which is phantom limb pain (PLP).

PLP occurs when amputees experience pain in a region that no longer exists (Rugnetta, 2020). Aside from pain, sensations that are also felt include touch, pressure, temperature, itching, and vibration. These are classed as exteroceptive perceptions and tend to be milder in comparison to the pain that is felt (Weeks, Anderson-Barnes & Tsao, 2010). There are numerous studies that attempt to decipher the cause of PLP, which tends to set in almost immediately after the amputation. The most cited cause, since the 1990s, is the neuroplastic change that occurs in the cortical areas of the brain. Following the amputation, the areas of the brain that are representative of the amputated appendage are overtaken by adjacent regions in the primary somatosensory cortex and the motor cortex (Rugnetta, 2020; Subedi & Grossberg, 2011).

Ramachandran & Rogers-Ramachandran (2000) wanted to depict cortical reorganisation in humans and was achieved using a Penfield map. This map is a representation of the brain based on the areas which correspond to the motor activities of the various body parts. After studying a group of amputees, it was found that there was up to 2-3 cm of reorganisation that occurred in the adult brain which is an indication of large-scale reorganisation. In a brain imaging undertaking by Flor et al. (1995) a strong positive relationship between the reorganisation of the somatosensory cortex and the intensity of PLP was discovered.

In a study conducted by Merzenich et al. (1984), amputations of the finger in adult owl monkeys indicated that following the amputation, the sensory input was taken over by the other digits. By conducting amputations to different extents, they were able to prove that the extent to which cortical reorganisation was recorded was dependent on the size of the deafferented area.

In an alternate study conducted to study the amygdala central nucleus neurons, it was uncovered that induction of arthritis led to synaptic plasticity. This plasticity was accompanied by a protein kinase A enhanced N-methyl-D-aspartate receptor, or NMDA, function. NMDA are cation channels found in nerve cells which are essential to the development of the central nervous system. To assess whether pain was inducing plasticity, an antagonist to the NMDA receptor was used which led to an inhibition of the synaptic plasticity seen through the changes to the NMDA receptors (Neugebauer et al., 2003). These changes played a significant role in contributing to the persistent pain after injury by modifying neuronal activity.

Aside from the above studies which discuss the reorganisation of the brain after amputation, a form of treatment – mirror therapy – used to alleviate PLP, also supports the ability of the brain to re-wire itself. In a study conducted by Ramachandran & Rogers-Ramachandran (1996), a patient experienced severe pain in his amputated arm. After using a mirror to help the patient visualise his hand, he realised that it was in a permanently clenched position. After repetitive therapy to imagine the fist unclenching, the patient was free of pain (Mansour et al., 2016). This depicts how the brain learning circuitry is an essential part of triggering chronic pain, and in teaching it to perform a certain action the pain could be overcome.

The research conducted on neuroplasticity and PLP indicate that there does seem to be some causality associated with amputations and re-wiring of the brain which triggers pain. This is representative of how the brain can cope with dire scenarios that the rest of body experiences, and develop mechanisms to optimise brain and appendage function, even though the outcome may not always be advantageous. Neuroscientists are yet to explain which aspects of cortical reorganisation is the true cause of the pain. 

References:

Apkarian, A.V., Baliki, M.N. & Geha, P.Y. (2009) Towards a theory of chronic pain. Progress in Neurobiology. 87 (2), 81–97. Available from: doi:10.1016/j.pneurobio.2008.09.018. 

Flor, H., Elbert, T., Knecht, S., Wienbruch, C., et al. (1995) Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature. 375 (6531), 482–484. Available from: doi:10.1038/375482a0. 

Lozano, A.M. (2011) Harnessing Plasticity to Reset Dysfunctional Neurons. New England Journal of Medicine. (364). Available from: https://www.nejm.org/doi/full/10.1056/NEJMcibr1100496. [Accessed on 11th November 2020]

Mansour, A.R., Farmer, M.A., Baliki, M.N. & Vania, A. (2016) Chronic pain: The role of learning and brain plasticity. Restor Neurol Neurosci. 32 (1), 129–139. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922795/pdf/nihms796061.pdf. [Accessed on 14th November 2020]

Michael M. Merzenich, Randall J. Nelson, Michael P. Stryker, Max S. Cynader, Axel Schoppmann, J.M.Z. (1984) Somatosensory cortical map changes following digit amputation in adult monkeys. The Journal of Comparative Neurology. 224 (4), 591–605. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/cne.902240408. [Accessed on 12th November 2020]

Neugebauer, V., Li, W., Bird, G.C., Bhave, G., et al. (2003) Synaptic plasticity in the amygdala in a model of arthritic pain: Differential roles of metabotropic glutamate receptors 1 and 5. Journal of Neuroscience.  23 (1), 52–63. Available from: doi:10.1523/jneurosci.23-01-00052.2003. 

Ramachandran, V.S. & Rogers-Ramachandran, D. (1996) Synaesthesia in phantom limbs induced with mirrors. Proceedings of the Royal Societ: Biological Sciences. 263(1369), 377-86. Available from: doi:10.1098/rspb.1996.0058

Ramachandran, V.S. & Rogers-Ramachandran, D. (2000) Phantom limbs and neural plasticity. Archives of Neurology. 57 (3), 317–320. Available from: doi:10.1001/archneur.57.3.317. 

Rugnetta, M. (2020) Phantom Limb Syndrome. 2020. Encyclopædia Britannica. Available from: doi:10.1097/00005053-195403000-00006 

Shaffer, J. (2016) Neuroplasticity and clinical practice: Building brain power for health. Frontiers in Psychology. 7 (JUL), 1–12. Available from: doi:10.3389/fpsyg.2016.01118. 

Subedi, B. & Grossberg, G.T. (2011) Phantom limb pain: Mechanisms and treatment approaches. Pain Research and Treatment. 2011. Available from: doi:10.1155/2011/864605.

Weeks, S.R., Anderson-Barnes, V.C. & Tsao, J.W. (2010) Phantom limb pain: Theories and therapies. Neurologist. 16 (5), 277–286. Available from: doi:10.1097/NRL.0b013e3181edf128. 

Yam, M.F., Loh, Y.C., Tan, C.S., Adam, S.K., et al. (2018) General pathways of pain sensation and the major neurotransmitters involved in pain regulation. International Journal of Molecular Sciences. 19 (8). Available from: doi:10.3390/ijms19082164. 

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