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Introduction:

A phantom limb is the continued sensation of a missing or amputated limb. This sensation can take the form of phantom limb pain, phantom limb sensation, and stump pain. Phantom limb pain is defined as any painful sensation that originates in the absent limb, and phantom sensation is defined as any sensation in the absent limb that is not painful. Stump pain is localized to the stump, meaning it does not originate in the absent limb (Woodhouse). About 95% of amputees are thought to experience phantom limb sensations and two thirds of those patients experience phantom limb pain. The most extraordinary thing about phantom limbs are the vivid reality with which sensations are felt. The sensations stemming from the absent limb are often so convincing that the patient continues to behave as if the limb is still present, so they might attempt to take a step on a missing foot or even reach for an object with a nonexistent arm (Melzack).

Phantom limbs are modality specific, meaning that they feel specific sensations such as touch, temperature, vibration, pressure, tingling, and itch (Giummarra). This is thought to be caused by the organization of different sensations that is kept throughout the entire sensory pathway all the way up to the cortex. It is not uncommon for the phantom limb to feel shortened or telescoped in nature. The limb often resembles its normal form but some patients report that portions of the limb are shrunken, deformed, or absent. The phantom limb most frequently adopts a habitual position and posture but sometimes the limb feels like it is stuck in a fixed position. The limb can also feel as if it is in an abnormal posture where the patient reports that their entire limb or portions of it are twisted out of shape, grossly intertwined, or floating in space (Figure 2). This can be very distressing for the patient and lead to feelings of uncomfortable pain (Giummarra). It is not uncommon for a patient to feel phantom limb sensations all the time while phantom limb pain often occurs intermittently for short but severe episodes several times a day. Pain felt prior to the amputation is often mimicked in the phantom limb and the patient feels as if they are still experiencing the past pain (Woodhouse). The pain is often described as a burning, cramping, or shooting sensation that can be anywhere from mild to severe (Melzack). Phantom limbs are not fully understood and neither is their root cause but by looking at the somatosensory system and other pathways involved in processing sensory information, great strides can be made to help patients deal with phantom pains and sensations.
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Somatosensory System:

The somatosensory system deals with sensation and perception and consists of the the peripheral sensory receptors, the ascending pathways, and the somatosensory cortex which is located in the postcentral gyrus. In this system, an adequate stimulus acts on a receptor which transforms that stimulus into an impulse which is then sent to the cortex so that the stimulus can be perceived or experienced. The somatosensory cortex is responsible for the sensation of touch, temperature, pain, and proprioception. Each of these sensations have different receptors that respond to different types of stimuli. The receptors responsible for touch are the Meissner's corpuscle, Merkel disk, Pacinian corpuscle, and Ruffini ending; these receptors are known as the cutaneous receptors. The receptors that respond to temperature are known as thermal receptors and they consist of cool receptors, warm receptors, heat nociceptors, and cold nociceptors. Pain receptors respond to noxious stimuli and are therefore nociceptors. Proprioceptors consist of muscle spindles, golgi tendon organs, and joint capsule mechanoreceptors (Kandel).

Spinal_Tract.jpg
Figure 1: Ascending Pathways to the Somatosensory Cortex http://virtual.yosemite.cc.ca.us/rdroual/Course%20Materials/Physiology%20101/Chapter%20Notes/Fall%202007/chapter_10%20Fall%202007.htm



Ascending Pathways:
The afferent fibers from the receptors for each of these sensations are projected to the dorsal horn of the spinal cord where they synapse with the dorsal root ganglion. From there the fibers split into two pathways, the medial lemniscal tract and the spinothalamic tract. The medial lemniscal tract travels in the dorsal column and carries tactile sensation and proprioceptive information to the thalamus and then to the somatosensory cortex (Figure 1a). The spinothalamic tract travels contralaterally up the spinal cord in the anterolateral column and carries painful and thermal sensations to the thalamus and finally to the somatosensory cortex (Figure 1b). The sensory information is kept somatotopicly organized throughout the entire pathway for each of the tracts (Kandel).

Somatotopic Organization:
The somatosensory cortex is located in Brodmann's area 1 and is somatotopicly organized, meaning that a specific body part's receptors are all grouped together and project to a specific region of the cortex. For instance, the hand receptors all project to one area of the cortex and all the foot receptors project to separate region in the cortex. Therefore the entire body is mapped out in the somatosensory cortex; each region of the cortex is devoted to a certain part of the body. The lower limbs are represented medially and the upper limbs are represented in the lateral portion of the cortex and the face is represented even more laterally. This orderly representation of each body part is known as the homunculus (Figure 3). As you can see, the hands and the lips have a much larger area of representation than other parts of the body.

Figure 3: Representation of the body in the somatosensory cortex. http://peripersonalspace.files.wordpress.com/2006/11/homunculi.jpg
Figure 3: Representation of the body in the somatosensory cortex. http://peripersonalspace.files.wordpress.com/2006/11/homunculi.jpg

Each type of sensation (touch, proprioception, ect...) is projected to a different portion of the somatosensory cortex and somatotopic organization is upheld in each of these areas. There are four different areas of the somatosensory cortex and they are areas 1, 2, 3a, and 3b. Area 1 receives input from rapidly adapting skin receptors, area 2 receives input from deep tissue receptors (pressure, joint position), area 3a receives input from slowly and rapidly adapting skin receptors, and area 3b receives input from deep tissue receptors (muscle stretch receptors). This enables the cortex to easily determine the sensation's modality and location (Kandel).

The somatosensory cortex also has output functions. It sends signals to other cortical regions both within the primary sensory cortex and to the posterior parietal cortex which functions as the association area of the cortex. The somatosensory cortex also has descending projections to the thalamus, basal ganglia, brainstem, and spinal cord (Kandel). The somatosensory cortex is involved in a complex web of connections and is in communication with many structures in the brain. It has a heavy influence on how and why humans perceive sensory stimuli the way that they do.











Phantom Limb Mechanisms:

The underlying cause and explanation of the phantom limb are unfortunately still under question. There is a large amount of speculation and hypothesizing going on which is leading to new research and is providing new understandings of phantom limb pathology. No theory seems to fit perfectly and when something seems to show promise, the mechanism can not be explained in full. Studying the somatosensory system's functions and characteristics have led to several theories that attempt to explain the phantom limb phenomenon. They can be categorized into three main groups: peripheral theories, central theories, and supraspinal theories (Woodhouse).

Peripheral Theories:
This theory postures that the peripheral nervous system is responsible for phantom limb pain. When a limb gets amputated neuromas form in the stump and are believed to be responsible for generating impulses that can be perceived as pain. Studies have shown that neuromas acquire the capability to spontaneously fire and they also have increased sensitivity to mechanical and other stimuli. Ion channel permeability in neuromas have also led to an increase in phantom limb pain (Woodhouse). If these neuromas truly are spontaneously firing and sending noxious sensory information up the anteriolateral column to the region of the somatosensory cortex where that limb was once represented then it makes consequential sense that painful sensations would occur. This theory has been even further supported by the fact that many patients find relief from pain by rubbing the stump of the amputated limb. Invasive treatments have been formulated based on the peripheral theory where the afferent axons are severed or the limb is amputated further down on the limb. These treatments were thought to eliminate the spontaneous signals from neuromas and therefore abolish phantom pain and they sometimes do provide complete relief. More often than not, these peripheral treatments only provide brief relief and then the pain returns in full force. Pain has also been reported in patients who have had a complete transection of their spinal cord to cut off the connection between the brain and the peripheral axons; this leads to the conclusion that neuromas may indeed contribute to the painful sensations, but they are by no means the sole cause (Woodhouse).

Central Theories:
This theory suggests that phantom limb pain is a result of central sensitization which is excessive activity in the spinal cord. This occurs as a result of the spinal cord loosing the afferent input from the missing limb. The neurons in the dorsal horn then get irritated and increase their excitability. Inhibition on those neurons is also reduced as a result of central sensitization (Woodhouse). The excitability of the neurons coupled with the reduced inhibitory effects results in a self-perpetuating loop that sends noxious signals up the spinothalamic tract to the cortex and once started this cycle is difficult to break. This theory has also been called into question by the fact that patients with upper body spinal cord injures still report pain and sensation in the lower legs. The dorsal root neurons for the lower limbs are below the break in the spinal cord and therefore their activity cannot be responsible for the pain the patient is feeling (Melzack).

Supraspinal Theories:
There are several supraspinal theories and each one of them suggests that the root cause of phantom limb pain is found above the spinal cord in the brain itself. Some studies suggest that the thalamus is responsible for phantom pain. The thalamus is considered the gateway to the cerebral cortex; ascending afferent information projects to the ventral posterior lateral nuclei of the thalamus before reaching the somatosensory cortex (Kandel). Stimulation of the thalamus has resulted in phantom limb pain for the amputee patients (Woodhouse). Bursts of activity in the thalamus have also been recorded in patients suffering from phantom sensations and pain. These findings seem to suggest that thalamic output to the somatosensory cortex is responsible for the painful sensations but surgical procedures done on this assumption have proved to be unfruitful. The reported areas of bursting activity in the thalamus have been removed to no avail (Melzack). The phantom pain persists even without thalamic output.

Another theory suggests that the cause of phantom pain can be found in the changes of the somatosensory cortex after a
Figure 4: Cortical Remapping after hand amputation. http://www.scholarpedia.org/wiki/images/thumb/6/6e/Homunculus_scholarpedia.jpg/300px-Homunculus_scholarpedia.jpg
Figure 4: Cortical Remapping after hand amputation. http://www.scholarpedia.org/wiki/images/thumb/6/6e/Homunculus_scholarpedia.jpg/300px-Homunculus_scholarpedia.jpg
n amputation. Cortical plasticity seems to be directly related to amputees feeling phantom limb pain. Brain imaging techniques have revealed that the topographic organization of the somatosensory cortex is not as fixed as was once thought. Studies have shown that cortical representation of the body can be remapped and reorganized; if part of the cortex is unused then the surrounding areas take over that space. For instance if the hand is amputated, the represented area for the hand in the somatosensory cortex is no longer in use. Since the face area is located directly next to the hand in the cortex, the face gets remapped onto the area of the missing hand (Figure 4). Figure 3a shows the original somatotopic representation with the hand still in tact while Figure 3b shows the face area taking over the hand's area after the amputation. Phantom limb pain seems to be correlated to the amount of cortical reorganization meaning that the more remapping of the cortex that occurs, the more pain the patient will feel in the phantom limb. One study showed that the mean shift in focus of cortical responsitivity to facial stimulation was 0.43 cm for patients who were pain free while the mean shift for patients experiencing pain was 2.05 cm (Flor). The patients experiencing pain had five times more reorganization occur than those who did not experience pain. Dr. Flor said, "The present findings suggest the intriguing possibility that the shift of the cortical map following amputation might be a potential neurophysiological basis of phantom-limb pain" (Flor Pg. 483). This correlation could possibly be related to an enduring nociceptive pathway from some pain in the past or it could be due to an imbalance between painful and non-painful inputs after deafferentation occurs (Flor). There is not really a concrete explanation as to why cortical remapping is correlated to phantom pain, but if this process could be prevented or reversed then it might provide some much needed relief for these patients.

Yet another theory suggests that phantom limb sensation and pain emerge from involvement from much more of the cerebrum than just the somatosensory system. This theory was developed by Ronald Melzack and he called it the neuromatrix theory where he stated, "that the brain contains a neuromatrix, or network of neurons, that, in addition to responding to sensory stimulation, continuously generates a characteristic pattern of impulses indicating that the body is intact and unequivocally one’s own. I have called this pattern a neurosignature. If such a matrix operated in the absence of sensory inputs from the periphery of the body, it would create the impression of having a limb even after that limb has been removed". This theory suggests that the neuromatrix consists of three main neural circuits in the brain that process sensory information simultaneously and share information with each other. The three systems are thought to be the somatosensory system, the limbic system which is responsible for emotion and motivation, and the cortical regions responsible for the recognition of self and the evaluation of sensory information which includes the parietal lobe. The neuromatrix theory suggests at these three circuits work together to process sensory information and provide the body with a sense of self and recognition of body parts as belonging to self. If a limb or body part is amputated or missing the neuromatrix no longer receives afferent information from that limb. This loss of sensory stimulation is thought to cause the neurons in the matrix to increase their firing activity to random bursting patterns that would elicit a burning sensation in the phantom limb (Melzack).









Conclusion:

Phantom limbs are a great mystery to the medical field and continue to be a very popular area for research. Phantom sensations and pain are both interesting to learn about and terrifying to imagine but as fantastical as they seem, they are unfortunately very much a reality to those suffering from them. It is interesting to contemplate what gives the ordinary sense of having an arm. This normal sense of an attached arm seems to come from the monitoring of feed-forward commands from the motor areas to the arm, the proprioceptive feedback from the muscles and joints, visual feedback, and a genetic scaffolding of ones own body image (Ramachandran). The brain is a powerful organ and it plays a large role in perception, perhaps an even larger role than originally thought. The brain might need to be looked at in a new light in order for phantom limbs to be understood. Perhaps the brain is more responsible for feeling and perceiving sensations than originally thought. Perhaps the brain is much more active than simply receiving sensory information and making sense of it. Ronald Melzack and others are challenging the old view of the brain and posturing that the brain does in fact "generate the experience of the body" (Melzack). This would mean that sensory information has a modulating role of the experience the brain is forming rather than a directly causal role (Melzack). This would also mean that if sensory input was lost from one part of the body then the brain would continue to form experiences and sensations for that body part. This is a radical and new way to look at how humans use their body to perceive and interact with the world and it could be the fresh perspective needed to crack the mystery of the phantom limb.

Glossary of Terms:


Somatosensory cortex- located in the post-central gyrus; it is the area of the cerebral cortex in which sensory signals are sent to be processed and integrated.
Thalamus- located between the cortex and the midbrain; it relays sensation, spatial information, and motor signals to the cerebral cortex.
Ruffini endings- cutaneous receptor located deep within the skin and in joints and are most sensitive to skin stretch. They are slowly adapting and have a large receptive field.
Meissner's corpuscles- cutaneous receptor located superficially in the skin; most sensitive to vibrations and movements across the skin (fluttering sensation). They are rapidly adapting and have a small receptive field.
Pacinian corpuscles- cutaneous receptor located deep with in the skin; sensitive to vibrating stimuli and unresponsive to steady pressure. They are rapidly adapting and have a large receptive field.
Merkel disks- cutaneous receptor located superficially in the skin; most sensitive to pressure and skin indentation. They are slowly adapting and have a small receptive field.
Nociceptors- sensory receptor that is sensitive to painful stimuli that causes tissue damage.
Thermal receptors- sensory receptors that are sensitive to temperature differences between the the skin and the objects that are touched.
Proprioception receptors- sensory receptors that are sensitive to the position and movement of one's own limb. Include muscle spindles, golgi tendon organs, and joint capsule receptors.
Medial lemniscal tract- located in the dorsal column of the spinal cord; it carries sensory afferent information from cutaneous and proprioceptive receptors to the the cerebral cortex.
Spinothalamic tract- located in the anteriolateral coumn of the spinal cord; it carries sensory afferent information from thermal and noxious receptors to the cerebral cortex.
Homunculus- pictorial representation of the anatomic divisions of the motor/somatosensory cortex; shows how much area of each cortex is designated to a specific body part.
Neuromas- nodules that grow at the cut end of a nerve; spontaneously fire and have an increased sensitivity to mechanical and other stimuli.
Central Sensitization- an increased response to stimuli that is mediated by an amplification of signaling in the central nervous system. The neurons in the spinal cord become hypersensitive.
Supraspinal- anatomical reference to any structure located above the spinal cord.
Limbic system- includes the hippocampus, amygdala, and limbic cortex; plays an important role in emotion, motivation, and long term memory.
Plasticity- refers to the ability of the brain and specifically the somatosensory/motor cortex to be molded or altered with experience.
Neuromatrix- a network of neurons that responds to sensory information and generates a pattern of impulses that gives the body a sense of self.
Parietal lobe- located posterior to the frontal lobe; integrates sensory information from both the somatosensory cortex and the visual cortex. Further processes sensory information.
Genetic Scaffolding- refers to the genetic makeup of one's brain that lays down a person's basic body image. It suggests that people are born with a genetic template for their body image.


Quiz:


1. The peripheral theories suggest that phantom limb pain is caused by what?
a) spontaneous firing of neuromas
b) decreased inhibition on neurons in the spinal cord
c) reorganization of the somatosensory cortex
d) all of the above

2. Cutaneous receptors send afferent signals to the cortex via the:
a) spinothalamic tract
b) anteriolateral column
c) medial lemniscal tract
d) medial lateral tract

3. What are the main modalities that the somatosensory system deals with?
a) pain, temperature, vision, and touch
b) touch, temperature, pain
c) vision, hearing, smell, and temperature
d) proprioception
e) b and d

4. All amputees that experience phantom limb sensation also experience phantom limb pain.
True
False

5. There seems to be a correlation between cortical reorganization and phantom limb pain.
True
False

6. Amputees cannot feel specific sensations such as temperature or pressure.
True
False

7. The hands and lips have the largest area of representation in the somatosensory cortex.
True
False

1. Explain why peripheral and central theories are not satisfactory in explaining the cause of phantom limb pain.

2. Explain the cortical reorganization that would occur after a hand amputation?

3. What three systems or circuits work together to form the neuromatrix?

Answers:


1. a)
2. c)
3. e)
4. False
5. True
6. False
7. True

1. Both central and peripheral theories fall short of a proper explanation because they cannot account for patients who still feel pain below a complete break of the spinal cord. In order for neuromas to cause pain they have to be able to travel up the spinal cord and send signals to the cortex but if the spinal cord is severed then the peripheral nerves would not be able to communicate with the somatosensory cortex. The same is true of the central theories. They cannot explain why spinal cord injuries still experience pain and sensation below the injury site. Central theories only work if the neurons in the dorsal horn can send signals up the spinothalamic tract.

2. After a hand gets amputated, the area in the somatosensory cortex designated for the hand no longer receives sensory information. That region of the cortex is no longer in use and because of the plastic nature of the brain, that area is now up for grabs. The somatosensory cortex represents the lower limbs medially and the the upper limbs laterally and the face has an even more lateral representation. This means that the face region is located directly next to the hand region of the cortex. Because of this anatomical set up, the face region is able to creep up and take over the old hand area of the somatosensory cortex.

3. The three systems that are thought to form the neuromatrix are the somatosensory sytem, the limbic system, and the cortical regions. The somatosensory system deals primarily with sensory information and the processing of that information. The limbic system deals with the emotional tags we place on specific sensory stimuli and it also deals with long term memory of past feelings. The cortical regions are responsible for further processing and evaluation of sensory information. All of these systems work together to form a sense of the self and respond to sensory stimuli.


Suggested Readings:


http://www.syn.sussex.ac.uk/phantomlimb/index.html
This link answers frequently asked questions and enables people to get involved in research. It also has interesting links for further information.

http://www.bbc.co.uk/radio4/reith2003/lecture1.shtml
This link is a lecture by V.S. Ramachandran where he goes over phantom limbs and multiple other interesting syndromes having to do with sensory perceptions.

http://www.radiolab.org/2006/may/05/
This link is an interesting and creative podcast that has a segment on phantom limbs featuring V.S. Ramachandran; it also deals with emotional perceptions, proprioception, and many other interesting issues.

http://www.transitiontoparenthood.com/janelle/energy/PhantomPain.htm
This link provides good information on what phantom limb pain is, what causes it, and gives helpful ideas on how to deal with it.

http://virtual.yosemite.cc.ca.us/rdroual/Course%20Materials/Physiology%20101/Chapter%20Notes/Fall%202007/chapter_10%20Fall%202007.htm
This link is a good and basic overview of the sensory system.



References:


Melzack R. (2006). Phantom LIMBS. Scientific American Special Edition, 16(3), 52-59. Retrieved from EBSCOhost.

Giummarra MJ, Georgiou-Karistianis N, Nicholls MR, Gibson SJ, Chou M, Bradshaw JL. (2010). Corporeal awareness and proprioceptive sense of the phantom. British Journal of Psychology, 101(4), 791-808. doi:10.1348/000712610X492558

Woodhouse A. (2005). Phantom limb sensation. Clinical & Experimental Pharmacology & Physiology, 32(1/2), 132-134. doi:10.1111/j.1440-1681.2005.04142.x

Kandell ER, Schwartz JH, Jessell TM. Principles of Neural Science. 4th ed. New York City: McGraw-Hill Companies, Inc., 2000.

Dougherty P. 1997. Somatosensory systems. Neuroscience Online. Houston: University of Texas Health Science Center. http://neuroscience.uth.tmc.edu/s2/ii2-1.html

Flor H, Elbert T, Knecht S, Wienbruch C, Pantev C, Birbaumer N, Larbig W, Taub E. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature 375: 482-484, 1995.

Ramachandran VS, Brang D. 2009. Phantom touch. Scholarpedia. http://www.scholarpedia.org/article/Phantom_touch (10 Dec 2010).