A think piece by E. Violakis, MD., MSc as published in Academia Letters, Article 3229. https://doi.org/10.20935/AL3229
A SYNTHETIC APPROACH
The phantom limb pain (PLP) is known since the 16th century, although the exact mechanism of action driving the phenomenon is yet to be deciphered. PLP occurs after the amputation of a limb and is frequently expressed either as a simple pain, a feeling of inconvenience, burning, itching or as a combination of all four. The amount of limb amputation in the USA accounts for 1.7 million people every year and about 86% of said procedure concerns lower limb amputations.[1] A great percentage of patients after undergoing a limb amputation do experience PLP through suffering some pain sensation, burning, itching and sometimes the feeling that the phantom limb is stacked in an inconvenient position. Research presents rates up to 78,8% for patients experiencing PLP with up to 51,2% reporting stuck pain. Furthermore it is worth mentioning that 58% of limb amputees claimed that they could move their phantom limp at their will.[2]
In uncovering the underlying mechanism of this rather impressive phenomenon four main theories have been proposed; the peripheral cutting nerve action potentials, the spinal cord default, the brain model or the central cortical remapping theory and the neuromatrix theory. The latter attempts to bring together and embody all the former.[4][6]
Through the lens of the first approach neuroma formation has been targeted as the reason for the abnormal electrical activation of the nerve. Novel theories connect the quantum tunnelling theory with this dysfunction. They claim that neuromas due to their large surface compared to the normal nerve extend the probability of spontaneous potassium atoms passing through the closed Na/K channels, entering the nerve cell membrane thus triggering the activation of the pain message to the brain. Although, it is an elegant theory that could potentially explain far more fundamental problems in biology and medicine and while the fact that local analgesic and anaesthetic medicine alleviating the pain supports such a theoretical lens, however it does not seem quite fit as a framework to offer a fully satisfactory explanation as to why for instance, patients with congenital aplasia of the limbs do face PLP.[3] Furthermore, the use of anaesthesia does not eliminate the pain in all patients even if it is injected in the plexus or epidural. This fact indicates that in some cases there is probably some central pathway, and not a peripheral one as the quantum tunnelling theory proposes.[6]
With regards to the spinal cord theory, after the amputation takes place and due to the continuous firing from the peripheral nerve, we observe certain structural changes in the dorsal horns neurons decreasing their ability to constrain and process any incoming pain messages. This unstoppable and rapid activation of neurons neutralizes the inhibition mechanism of GABA and glycenergic interneurons of the spinal cord. Another phenomenon that takes place is when the brain derived neurotrophic factor (BDNF) released by the microglia sends signals to the spinal lamina I neurons in the dorsal horns, it somewhat generates a hyperexcitable spinal cord; one that does not filter or downsize any pain messages.[6][7]
After limb amputation and axotomy another interesting event occurs; neuropeptides such as substance P, calcitonin gene-related peptides (CGRP), and somatostatin that are the main pain regulators in the spinal cord, present in sensory neurons and μ-opioid receptors are down regulated. This can explain the fact that opioids have little or no effect upon the neuropathic pain. In addition, while substance P is decreased in C and Aδ-afferents, the amputation destruction of peripheral nerves triggers Aβ fibres to express substance P, which broadcasts nociceptive signals “through primary afferent fibers to spinal and brainstem second-order neurons”. [9] Other neuropeptides such as vasoactive intestinal peptide (VIP), galanin, neuropeptide Y (NPY), cholecystokinin (CCK), and pituitary adenyl cyclase activating polypeptide (PACAP), which are normally expressed in low levels within the sensory neurons, are now greatly unregulated. The aforementioned events all describe a reorganization among the neuropeptides levels.[8] Except from such a reorganization within the neuorpeptides, fundamental changes occur at the structural distribution of the neurons as well, with new corticolspinal maps and connections being created. Knowing these new pathways alongside their physiology that is claimed to mimic the mechanism of learning, we could achieve a better rehabilitation for amputated patients.[10]
Concerning the brain model of PLP, there two possible sub-theories. The first claims that when the limb is cut the projection of the limb in the analogue place within the somatosensory cortex disappears and thus a gap of connections is created .The closest somatosensory cortex comes “to the rescue” to fill in this gap. This phenomenon is called topographical remapping.[11] It seems that there is an interaction between such a remapping and signals from the periphery, as the creation of neuroma in the amputated limb and the degeneration of C-fibers have a positive effect on it. Especially, C-fibers play an import role in maintaining the cortical maps of the brain.[6]
The second sub-theory proposes that there are multiple neuro-links that connect neighbour sides of the brain and in our case between various areas in the somatosensory cortex. Those neuro-links pre-exist but are and remain mostly silent. However, when the main connection with the limb is cut off the previously silent links are now turned on.[11] Further support for this theory can be found in such incidences when several amputees who underwent hand amputation -and experience PLP- whenever touched at specific areas of their face they experience a variety of sensations in their phantom hand. It hence seems that a specific area of their hand is somewhat linked to certain areas of their face. Mainly, their thumb is related to their cheek and the index finger to an area exactly above their upper lip. This map is not only accurate but standard and constant.[11] It is thought that the brain’s capacity for plasticity (neural plasticity) which drives changes in the pathways of our neurons is the key towards understanding PLP and especially this rather curious correlation found between phantom hands and areas of the face. Changes to the cortical areas of the brain observed -through controlledstudies- in amputated patients as well as new pathways of neurons being formed after patients undergo a stroke, show us the ability of our neuron system to adapt to changes. Those rather extraordinary facts can lead us towards viewing the brain through the lens of “the Penfield man” concept, which depicts the connection between the somatosensory cortex and our body’s surface. In the same light, such a conceptual framework can explain why lower extremity amputation is connected with disorders in micturition and defecation.[11][1]
On a final note, PLP can be approached through the neuromatrix theory.This is a more holistic approach supporting the premise that a whole special system of neural network exists in the brain reacting to any type of pain trigger but it can also -under certain circumstances – act autonomously. This neural network is highly complicated and there is an enhancement of its activation when the pain becomes chronic. Hence even minimal signals from the periphery can generate great activation of pain response in the neuromatrix; a simple and minimal pain stimulus can activate a grave brain pain response. [5][13]
The propreoceptive memory can be viewed as another phenomenon neatly explained by the neuromatrix model. In this event after a limb amputation takes place and despite the fact that the input signal transfers the information that there is a defect with the amputated limb, the brain’s propreoceptive memory remains in the previous reality; that of the phantom limb still being there. On one final note, this theory can also explain why for many amputees central and peripheral analgesia has no or little effect on.[5] Indeed prophylactic analgesia seems to have no effect in the presentation of PLP, although NMDA receptor antagonist in the peri-operative and postoperative time leads to a positive effect in the pain management.[12] Another interesting postulation driven by this theory is that if the pain is pre-established for a long period of time with the spinal and cortex synapses having changed because of it, when the remapping takes place the first response will be pain. This is because the pain alters the construction of the cortex being also imprinted in the proprioceptive memory of the patient. [14]
Taking all these explanatory models into account, a PLP relief intervention approach could be discovered within the field of medical acupuncture. Acupuncture is a healing method that first appeared about 3000 years ago in ancient China. Recent studies demonstrated the effectiveness of the method especially for the management of pain, but far more extensive research remains to be done to fully evaluate this ancient technic and its efficacy.[15]
Regardless, a special method of acupuncture may be of some merit to further explore when it comes to PLP; electroacupuncture…
[read the rest on Academia letters, Article 3229. https://doi.org/10.20935/AL3229 ]
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