Phantom Limb Syndrome

In normal conditions, our bodies receive and process millions of different tactile sensations every day. We have the incredible ability to detect and locate each and every one of these sensations via the delicate tactile receptors and specific pathways that carry this information to our brain for processing. This ability allows us to detect and react to outside stimuli making us a dynamic part of our environment. However, sometimes our body does not always relay the correct information to our conscious perception. One such case can be seen in regards to the Phantom Limb syndrome. Phantom Limb syndrome occurs when individuals experience somatic sensations in areas that no longer exist in their bodies i.e. legs, arms, breast, penis, hand, foot etc. due to amputation, deafferentation or a congenital defect.[1,4] These phantom sensations range from harmless feelings of pressure to extreme and debilitating pain. The cause and source of phantom limb sensation are not completely understood, however, current studies indicate that the sensations originate within the cerebral cortex. The treatment of this phenomenon is still being studied and current options range from over the counter pain killers, therapy, and surgery.[1,2,8]


Overview of the somatosensory process:

  • Sensory receptors- cutaneous, proprioception, pain (free nerve endings)
There are five cutaneous receptors cells associated with sensation, merkel, missner, raffini, pacinian and free nerve endings. The first four receptor information travels along A-beta nerve fibers to the spinal cord. The fifth receptor’s information travels along A-delta and C fibers to the spinal cord. The receptor cells are located in specific regions within the skin and each one is sensitive to a particular mechanical action. These specific mechanical functions produce the adequate stimulus that is needed to propagate an action potential to the Spinal Cord.[9,10]
  • Merkel cells:
Have small receptor fields near the surface of the skin and as such are very sensitive to detail. They are mostly used for discerning the corners, edges and points, of objects.
  • Missner Cells:
Have small receptive fields near the surface of the skin and are densely packed in areas such as fingertips. These cells are responsible for defining small motion, rubbing and slippage of objects against your skin.
  • Raffini Cells:
Have large receptive fields and are sensitive to stretch. It is these cells that are active when you stretch your fingers and you feel your skin becoming taut.
  • Pacinian Cells:
Consist of cells with large receptive fields and are associated with high-frequency vibrations. It is these cells that are active when you feel your computer buzzing during charging.
  • Free Nerve endings:
Theses cells are the cells that propagate thermal and pain information. They are open nerve endings and are near the surface of the skin.

Phantom limb 1.png
Figure 1 Diagram of the five different cutaneous receptors.

Figure 1

There are also two separate receptors that provide the body with Proprioception information the Golgi Tendon Organ and the Muscle Spindle.
  • Golgi Tendon Organ (GTO)
The GTO is embedded within the tendon of a muscle and its nerve endings are interwoven in series with the collagen fibers of that tendon. When the muscle contracts it is shortened putting stress/tension on the fibers of the tendon. This tension pinches the Ib fiber of the GTO and opening mechanically gated receptors and ultimately causing an action potential to be propagated to the spinal cord.[9,10]
  • Muscle Spindle
The muscle spindle is a receptor that lies in the belly of the muscle. When a muscle is flexed, the muscle spindle experiences a change in length of its intrafusal fibers and relays that information via the Ia and II afferent fibers to the spinal cord. The muscle spindle also has efferent gamma motor neuron innervation that keeps the intrafusal fibers taut at all times so that even if the muscle is relaxed the intrafusal fibers will not be slack and can still relay length information to the central nervous system.[9,10]

Phantom limb 2.png
Figure 2 Diagram of the Muscle spindle within the muscle and the GTO within the tendon


Figure 2

All of the sensory information coming in from the periphery enters the spinal cord and travels along one of two tracts, either the Dorsal Column Medial Lemniscal pathway or the Anterolateral pathways. [9,10]

Dorsal column medial lemniscal (DCML)
Fibers from the proprioceptive (Ia, II, Ib) and discriminative touch receptors (Ab) travel along this tract. The DCML consists of two posterior column tracts the gracilis and the cuneatus. These columns house fibers from different body regions. The gracilis fasciculus contains fibers from the lower body, T7 and below and the cuneatus fasciculus contains fibers from the upper body, T6 and above. Figure 3[10,11]
Once information enters the spinal cord via these fibers it immediately hooks into the dorsal columns traveling ipsilaterally in the cuneatus and gracilis fasciculi until it reaches the cuneatus and gracilis nuclei in the medulla. Here the neuron synapses onto the second order neuron and decussates. The second order neurons then enter the Medial Lemniscus terminating on the ventral posterior lateral nuclei (VPL) of the thalamus. Once the proprioception and discriminative touch information have reached the thalamus it will then be projected to Broadmann’s area 3a, 3b, 1 and 2 via the third order neuron.

Anterolateral pathways
This pathway transmits information from the free nerve ending pain receptors and thermoreceptors (III IV and C). The information coming into the spinal cord from these sensory receptors enters the spinal cord, ascends and descends in the Tract of Lissauer and then immediately decussates at the spinal cord level. The sensory information travels contralaterally in the anterolateral tract up the spinal cord and terminates in the specific areas of each of the three separate tracts of the anterolateral tract. [10,11]

  • Spinothalamic: This tract terminates in the somatosensory cortex and is associated with awareness of pain location. Figure 4a
  • Spinoreticular: This tract has projections that terminate in the reticular formation and is associated with the emotional aspect of pain. The awareness of “Ouch that hurts”. Figure 4b
  • Spinomesencephalic: This tract has projections that terminate in the midbrain and is associated with pain modulation and the knowledge that it feels better. Figure 4c


Phantom limb 3.png
Figure 3 image of the DCML tract as they ascend up the spinal cord to the cortex.
Phantom limb 4.png
Figure 4 image of the Anterolateral tract as they ascend up the spinal cord to the cortex.

Figure 3 Figure 4


Somatosensory Cortex

The final termination for all raw sensory information is the primary somatosensory cortex. This area is located on the post-central gyrus of both the right and left hemispheres of the brain. Within these gyri, there are four separate Broadmann areas 3a, 3b, 1 and 2. Each one of these areas receives specific information from particular receptors. For instance, Broadmann’s 3a is associated with proprioception information from the GTO and muscle spindle and area 3b receives input from the cutaneous receptors merkel and raffini. Within each Broadmann area, there is a full body representation homunculus such as is seen in Figure 5. Although each part of the body is represented along the post-central gyrus not all of the body parts have equal representation and as such have the distorted appearance of the homunculus man below. Larger body parts are associated with a larger cortical representation.[9,10,11]


Phantom limb 5 .png
Figure 5 Representation of the homunculus somatotopic representation of the body on the cortex. The un-proportional size of appendages represents increases cortical representation.

Figure 5




Phantom Limb Syndrome


The phenomenon of phantom limb syndrome occurs when an individual experiences tactile sensations that seemingly originate from a phantom limb or body part that is non-existent. This phenomenon has been reported to occur in amputees, individuals that have experienced deafferentation, paraplegics, and individuals who have been born with a missing limb. [1,7] A majority of individuals who experience Phantom Limb report that over the years the limb seems to “telescope” [1,7,8] retract into the remaining stump. For example, if an individual underwent a lower leg amputation, from the knee down, this patient might very likely feel as though his phantom foot was abutted to his thigh. Figure 6

Another interesting habit of the phantom limb is for it to fill in the prosthetic that is administered for treatment.[7] This is often considered a positive outcome, allowing the patient to feel as though the prosthetic is his real arm. (1) A similar case occurs in deafferented or paraplegic individuals, their phantom fills the sensationless limb often causing them to feel as though they do not have a phantom. However, once the patient attempts to move their limb they find that they have no control over it.[1,7,8]

There are a number of sensations that are felt by phantom limb patients, “specific position, shape, or movement of the phantom, feelings of warmth or cold, itching, tingling, or electric sensations…”(Lancet (29) 182-189) [4] The feelings that that come from these phantom limbs are extremely real and are reported to feel exactly the same as sensations from intact limbs.[7,8]

Although many individuals who experience phantom limb syndrome report having normal harmless sensations, there is a majority of individuals who also report feeling extreme pain in the limb that does not exist. Naturally this is a cause for concern especially since treatment is complicated due to the fact that there is no limb to treat.

The disappearance of Phantom limb sensation and pain often occurs over time however, this is not always the case and research is still being performed to learn how to best treat the pain.[4,7]
Phantom limb pic (neuroscience).jpg
Figure 6 Common areas that are associated with phantom limb syndrome. Telescoping is also represented as the end of the appendage retracts into the remaining stump.

Figure 6


The causes of the debilitating Phantom Limb Pain are not completely known, however, there are two leading theories proposed by R. Melzack and Head and Holmes that hold to be the most probable.
The oldest and most accepted view for the cause of phantom pain comes from Head and Holmes, during their research of Sensory disturbances from cerebral lesions. HTey developed the idea of a the human body being mapped out on the postcentral gyrus creating the body schema theory or Homunculus theory.[5,6,7] As was discussed above each area of the body has somatotopic representation on the post-central gyrus of the primary somatosensory cortex. This allows the brain to receive sensations from specific areas in the body and be able to pinpoint exactly where the sensory information is coming from. However, these areas are not completely fixed, but rather it has been shown that the cortex is quite plastic, adapting and changing its' somatotopic representation as the body's needs change.[3,9,10,11] For example, if one were a right handed violin player, months, and years of continued and increased use of that hand will cause the brain to reorganize the neuronal connections in the cortex, allowing the right-hand area to broaden and take over more of the cortex. Ultimately providing the violin player better control and fine tuning abilities in her right hand. It is this very process, of somatotopic expansion, that is believed to occur when one loses a limb and still registers somatosensory feeling. The missing limb’s area in the cortex is taken over by the neighboring body part's cortex representation [3] and stimulation of those areas leads one to believe that the sensations are actually coming from the missing body part. Research done at Lancet have shown similar occurrence in regards to hand amputation and mouth somatosensory expansion. It was found that after the hand amputation the somatotopic representation of the mouth began to spread to the hand region, this was followed by correlated “phantom pain” in the hand whenever the face was stimulated. See Figure 7. Through this experiment and many others like it, researchers have come to the conclusion that the source of Phantom limb syndrome is due to the stimulation of neighboring somatotopic areas. When these areas on the body are stimulated the cortex receives activity where the amputated limb formally projected causing the individual to feel as though her missing limb is actually experiencing sensations.[5,7]


phantom limb 7 .png
Figure 7 This figure shows how the mouth representation on the amputated hand side has taken over the hand homunculus area. Activity is modeled from an Neuroimaging magnetic source


Figure 7


The second viewpoint of how Phantom limb syndrome occurs is postulated by R. Melzack. Melzack does not agree with Head and Holmes’ body schema theory. Melzack claims that their theory is not sufficient in explaining the sensations and reality of the phantom limb, but rather it is too vague and does not postulate actual neural mechanisms to explain the postural body schema. [7] Melzack’s own theory consists of a Neuromatrix which is comprised of the “thalamus and somatosensory cortex, the reticular formation, the limbic system, and the posterior parietal cortex”(Lancet (29) 182-189) [4,7] that incorporates the “self”. This Neuromatrix then outputs a personally specific Nurosiginature that is influenced but not run by environmental stimuli. Melzack explains the actual phantom feelings by stating that “An amputation would create an abnormal input into the Neuromatrix owing to a lack of normal sensory activity or over-activity related to the abnormal firing pattern of damaged nerves. This input would lead to an altered Neurosignature and the experience of a phantom.” (Lancet (29)182-189) [4] Here Melzack attributes the phantom feelings, I.e. pain, pressure, itch, thermal changes, to a mismatch in the Neuromatrix which in turn outputs an abnormal Neurosignature leading to a phantom. Although Melzack's Neuromatrix theory includes the neurological structures that are believed to contribute to phantom limb phenomena, it is difficult to test due to the numerous inputs it claims to have and it does not explain fully why some individuals experience pain and others do not.[1,4,7]

Treatment:

There have been many different approaches to treating phantom limb pain. The wide range of options are due to the fact that the one, the real cause has not been identified and defined thus leading to difficulty in treatment. And two, each individual experiences a very subjective and personally specific pain, making a universal treatment option almost impossible. The following list is provided by the KMUJ: Khyber Medical University Journal. This list contains many, although not all, of the current treatment options available to Phantom limb patients. [1,2,4,6]
Pharmaceutical options:
  • Preemptive use of analgesics and anesthetics: Taking pre-surgery pain medications so as to have no pain before the surgery in hopes that the pain will not continue after the surgery.
  • Non-steroidal Anti-Inflamma- tory Drugs (NSAIDs): These are used to decrease the nociception both peripherally and centrally. [1]
  • Tricyclic antidepressants (TCA): Antidepressants are a common medication used for neuropathic pains, however, they are not always effective in every individuals case of Phantom Limb Pain.[1]
  • Anticonvulsants and Serotonin Norepinephrine reuptake inhibitors: Show mixed results in abetting phantom limb pain but still an option. [1]
  • Opioids: Provide analgesia by binding to central and peripheral opioid receptors. Although effective, their use is debated due to the high addiction probability.[1]
Non-Pharmaceutical options
  • Transcutaneous Electrical Nerve Stimulation (TENS) – stimulation of the damaged nerves at the sight of amputation. [1]
  • Mirror Therapy: Using a mirror to reflect the intact limb and attempting to manage the pain by addressing the reflected limb. [6]
Phantom 8.png
Figure 8 Mirror Therapy

Figure 8
  • Surgical interventions: Usually used after all other methods have failed. Reorganization of nerve as the stump of amputated limb and Neurectomy are among the most common procedures.[1]

Conclusion

Throughout this article, we see how the body is designed to function in a very specific way. Under normal conditions, it has an amazingly intricate system for conveying information from the environment to the cortex so that the individual may respond in an advantageous manner. Phantom Limb Syndrome is an example of the body attempting to perform its' proper functions while lacking essential parts to the system. It is known that the origin of the phantom limb sensation arises from the cortex, however, there are differing views on how exactly the cortex conveys that information. There is the idea that the somatotopic representation in the cortex adapts to the lack of sensation from the missing limb and takes over that area leading to sensations coming from the "Phantom limb". There is also Melzacks viewpoint that Phantom sensations arise from the abnormal Nerurosignature that is produced by the lack of input from the lost limb. Although there is no specific answer to the cause of Phantom limb syndrome there is still a combined effort to understand this syndrome more completely. Since the condition is not understood perfectly and do to the very individual specific aspects of this condition, a universal treatment does not exist however there has and continues to be a great effort to find a better way of treating this condition.


Terms

  • Merkel- small receptor, slowly adapting cutaneous receptor
  • Missner- small receptor field, rapidly adapting cutaneous receptor
  • Raffini- large receptor field, slowly adapting cutaneous receptor
  • Pacinian- large receptor field, rapidly adapting, cutaneous receptor
  • Free nerve endings- open ended neuron that transfer pain and thermal information
  • Muscle Spindle- proprioceptive receptor embedded within the muscle belly. associated with muscle length.
  • Golgi Tendon Organ(GTO)- proprioceptive receptor within the muscle-tendon complex. associated with muscle tension.
  • Dorsal column Medial lemniscal (DCML)- ascending tract that carries cutaneous and proprioceptive information to the cortex
  • Anterolateral pathway- ascending pathway that carries thermal and pain information to the cortex.
  • Homunculus- somatotopic representation of the body on the cortex gyri
  • Neuromatrix- the combination of neurological structures that Melzack uses to describe the all inclusive idea of self
  • Nurosignature- the output of each individual's Neuromatrix
  • Neurectomy- surgical removal of all or part of a nerve.


Further Reference Sources


  • Detail information regarding the cutaneous receptors and the ascending pathways that are described can be found in the textbook Neuroscience Online: Link
  • For more detail of the treatment options and their success rates see: This Link 1 Provides an article that gives an overview of Phantom lLmb Syndrome and a detailed description of the treatments and their success.
  • The Link 2 leads you to a case series on Phantom Limb Treatment, that can be purchased. This Article explores whether or not a combination of observation and imagination of movements can reduce phantom limb pain. However, the same article can be found in EBSCOhost titled, Decreasing Phantom Limb Pain Through Observation of Action and Imagery: A Case Series, free of charge.
  • The complete research article by R. Melzack, giving full description of his Neuromatrix theory can be found here



Quiz

True/False:

  1. All individuals who experience phantom limb syndrome experience debilitating pain.
  2. Everyone agrees on the cause of Phantom limb Syndrome
  3. One of the theories for explaining Phantom limb syndrome involves somatotopic areas in the cortex taking over areas of the amputated limb.
  4. There is a tried and true treatment for most individuals with Phantom limb pain.
  5. Sensory information ascends to the cortex in several different tracts including the DCML and anterolateral tracts.
  6. The Neuromatrix involves the peripheral nervous system.
Short Answer:
  1. What is the funny looking man called?
  2. What is the term that Melzack uses to describe the areas of the brain that create a Neurosignature?
  3. What are the 5 tactile sensory receptors?
  4. What is the term that describes the retraction of the phantom limb into the remaining stump?
  5. Name two different types of treatment that have been used to treat Phantom Limb pain.
Short Essay:
  1. Give a brief summary of Head and Holmes’ explanation of Phantom Limb Syndrome.
  2. Why is it difficult to treat phantom limb pain?
  3. What is an argument against Melzack’s theory of the Neuromatrix?



References

  1. Anwar, F. (2013). PHANTOM LIMB PAIN: REVIEW OF LITERATURE. Khyber Medical University Journal, 5(4), 207-212 http://www.kmuj.kmu.edu.pk/article/view/10914/pdf_2
  2. Beaumont, G., Mercier, C., Michon, P., Malouin, F., & Jackson, P. L. (2011). Decreasing Phantom Limb Pain Through Observation of Action and Imagery: A Case Series. Pain Medicine, 12(2), 289-299. doi:10.1111/j.1526-4637.2010.01048.x
  3. Chen, R., Cohen, L., & Hallett, M. (2002). Nervous system reorganization following injury. Neuroscience, 111(4), 761-773. Retrieved November 10, 2015, from http://www.smpp.northwestern.edu/savedLiterature/ChenEtAl2002NervousSystemRecoveryFollowingInjuryNeuoroscience111(4)761-73.pdf
  4. Flor, Herta. Phantom-limb pain: characteristics, causes, and treatment The Lancet Neurology, Volume 1, Issue 3, 182 – 189 http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(02)00074-1/fulltext
  5. Head H, Holmes G. Sensory disturbances from cerebral lesions. TheLancet1912 179(4612): 144-52
  6. McCormick, Z., Chang‐Chien, G., Marshall, B., Huang, M., & Harden, R. N. (2014). Phantom limb pain: A systematic neuroanatomical‐based review of pharmacologic treatment. Pain Medicine, 15(2), 292-305.
  7. Melzack R. Phantom limbs, the self and the brain. The D.O. Hebb Memorial Lecture. Canad. Psychol. (1989);30:1–14. http://www.psych.mcgill.ca/perpg/fac/melzack/phantom_limbs.pdf
  8. Purves, D. (2008). Phantom limbs and phantom limb pain Box b. In Neuroscience (4th ed.). Sunderland, Mass., MA: Sinauer. http://www.ncbi.nlm.nih.gov/books/NBK10967/box/A691/?report=objectonly
  9. Tsuchitani, Chieyeko Ph.D. (2015). Somatosensory Pathways. (Section 1-10, Chapter 4) Neuroscience Online: An Electronic Textbook for the Neurosciences | Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston. Retrieved December 1, 2015. http://neuroscience.uth.tmc.edu/s2/chapter04.html
  10. Byrne, J. (Ed.). (2015). Neuroscience Online: An Electronic Textbook for the Neurosciences | Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston. Retrieved December 2, 2015, from http://neuroscience.uth.tmc.edu/index.htm
  11. Tsuchitani, Chieyeko Ph.D. (2015). SomatosensoryProccess. (Section 1-12, Chapter 5) Neuroscience Online: An Electronic Textbook for the Neurosciences | Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston. Retrieved December 1, 2015, http://neuroscience.uth.tmc.edu/s2/chapter05.html


Quiz answers
True/false:
  1. F
  2. F
  3. T
  4. F
  5. T
  6. F
Short Answer:
  1. Homunculus
  2. Neuromatrix
  3. Merkel, missner, raffini, pacinian, free nerve ending
  4. Telescoping
  5. Two off the list