Sensory+Perception

=PHANTOM PAIN = by Liz Snyder


 * What is phantom pain? **

Amputee patients commonly continue to experience sensation in limbs that have been surgically removed. These sensations may be painless feelings of tingling, temperature, or itching, in which case the term “ **phantom sensation** ” is used. Sometimes, however, patients experience squeezing, throbbing, or burning pain coming from their amputated limb, and this is called “ **phantom pain** ”. It must be noted that this pain is not coming from the remaining stump of the amputated limb, but rather from the actual body part that is no longer present.



Approximately 84% of amputee patients claim to experience some type of phantom sensation, and around 72% report feelings of phantom pain (2). The sensations typically appear quickly following the surgery, usually within a few days after amputation. Most commonly, phantom pain is felt in the distal areas of the amputated limb, such as the feet, hands, fingers, and toes. In fact, it is possible for the proximal portion of the phantom limb to fade out of perception over time and for only the distal portion to remain, a phenomenon known as "telescoping" (2). It is possible for phantom pains and sensations to decrease over time, however many amputees report a vivid sensory awareness of their phantom limb for the rest of their lives. It is also possible for children born without limbs to experience phantom pains and sensations (5,7,8). Originally, reports of phantom pain were thought to be cases of psychological disturbance or "wishful thinking." However, a plethora of scientific evidence has confirmed that there is concrete physiological backing for these sensory events.

**Why is phantom pain important for this class?**

**
 * Phantom pain is a fascinating and controversial topic in Neurophysiology today that incorporates ideas about peripheral nerves, the spinal cord, ascending pathways, the cortex, and plasticity. Although we never specifically addressed this topic in class, attempting to understand phantom pain and the mechanisms behind it will be an excellent way to test your knowledge of the underlying physiological processes.

**What causes phantom pain?**

A variety of mechanisms exist for phantom pain. These various causes can be found in the nerves at the site of amputation, in the spinal cord, and within the brain.

__At the nerve:__

When an amputation is performed, peripheral nerves feeding the limb become severed and damaged. Painful tumors called **neuromas** may begin to grow on the frayed nerve endings. Neuromas are extremely irritable and sensitive to mechanical, electrical, and chemical stimulation. They readily send nociceptive input up through the spinal cord, and it is theorized that this input travels to the area in the **somatosensory cortex** originally designated for the amputated limb. Therefore, the brain concludes that the amputated limb is still present and phantom pains emerge (2,5,7).

__At the spinal cord:__

Amputation can cause painful reorganization and adjustment at the level of the spinal cord. Since the spinal cord is no longer receiving information about touch, pressure and proprioception from the amputated limb, the central terminals of the afferents that would have carried this information can become disoriented. Typically, fibers carrying this information would ascend up the posterior columns of the spinal cord, however in the case of amputation it is possible for the remaining afferents to sprout into the lamina of the anterolateral tracts, and synapse there with second order nociceptors that relay information about pain. Therefore there may be an excess of pain information traveling up the anterolateral pathway from fibers previously making up the dorsal column tracts (2).



__In the brain:__

//Cortical Plasticity.// Recall that the sensory and motor cortices are topographically organized. This organization is referred to as the **homunculus** and is depicted below.

This image shows that afferents from every body part send their information to a designated area of the somatosensory cortex. Following an amputation, portions of the cortex become unused and cortical **plasticity** or "remapping" occurs. Neighboring areas of the cortex begin to innervate the newly vacant areas. There are two proposed theories for how this remapping occurs: 1) neighboring areas of the cortex sprout and grow new nerve fibers that travel to and subsequently innervate the unused areas or 2) a number of redundant connections already exist in the cortex, but are masked by the most prominent synapses in each cortical area. When the prominent synapses become absent, underlying connections become noticeable (7).

Numerous studies have confirmed that cortical plasticity highly contributes to phantom pain (3,5-7). Dr. Ramachandran, author of //Phantoms in the Brain: Probing the Mysteries of the Human Mind//, discovered striking evidence for this in one his amputee patients, Tom. Tom experienced sensation in his phantom arm when Dr. Ramachandran touched him on the face, specific areas of the face correlating with specific areas of the phantom arm. Glancing back at the image of the homunculus, notice that the cortical portions designated for the hand are adjacent to the portions designated for the face. It is thus easy to see that the sensory fibers from Tom's face had spread to their neighboring areas. They were now responsible not only for facial regions of the cortex but also for the hand and arm regions (p 29).

Normally, cortical plasticity is a positive function aimed at restoring and maintaining sensory and motor awareness. However, in amputee patients, this mechanism becomes dysfunctional and harmful (3). In fact, the greater the amount of cortical remapping, the greater the amount of pain a patient will experience (4).

//The Neuromatrix.// Though not completely understood, a number of studies concerning the neuromatrix have suggested phantom pain is also influenced by higher brain centers. The neuromatrix consists of the cortex, the thalamus, and the limbic system, and the **neuromatrix theory** states that these structures make up an integrated processing system (2). The thalamus and limbic system play a role in conscious body awareness (1), and a study by Moseley et al found that it is possible to modify this awareness in phantom limbs despite the lack of proprioceptive input (6). Amputee patients were successful in learning to perform an anatomically impossible task with their phantom limb, which suggests that the **body schema**, the mental representation of the body, can be altered solely by internal brain mechanisms without supplementary information cutaneous and proprioceptive receptors from the limb (6). It is fascinating to note that even in the absence of afferent information from the limb, the efferent signals from the neuromatrix continue to the limb continue, providing the phantom limb with a perception of sensation and pain (2).

**How is phantom pain treated?**

//Pharmaceutical.// There is no specific pharmaceutical treatment for phantom pain, but frequently prescribed medications include antidepressants, anticonvulsants, medications to increase blood flow for burning pain and muscle relaxants for cramping pain (2).

//Surgical//. Surgical techniques exist to alleviate phantom pain, however they are often found to be ineffective and are typically reserved for only the most critical patients who have experienced no other success. Surgical procedures include removal of neuromas, dorsal rhizotomies (cutting of the afferent sensory fiber entering into the spinal cord), cordotomies (cutting of the dorsal column to prevent transmission of information to the brain), and even thalamic and cortical lesions (2,7). Dr.Ramachandran theorizes that these procedures are rarely successful because the phantom pain results from a conglomeration of information from all these various locations rather than one localized area.

//Physical rehabilitation//. A popular physical rehabilitation technique for phantom pain is **mirror box** therapy. This technique was invented by Dr. Ramachandran and works on the principle of altering mental body schema. Below is a diagram of a mirror box.

The patient is instructed to insert one arm through the circular opening, and the phantom arm through the other. The box is divided in the center with a mirror so that, when looked at from an angle, the patient has a view that projects a reflection of the real arm into the visual space occupied by the phantom arm. In this way, the patient is able to view their phantom limb as normally functioning and pain-free. The brain thus recreates the body schema and generally positive results are seen (2).

//Preventative treatment//. It has been found that treating a painful limb before amputation is extremely helpful in deterring excessive phantom pain sensations. Patients' phantom pain generally resembles the pain experienced before amputation, and patients who do not experience much pain prior to surgery are less likely to develop phantom pain. This once again reinstates the fact that mental body image representation is very strongly learned and maintained by the brain (2,5,7).

**Conclusion**

Phantom pain is a neurophysiological phenomenon that involves the peripheral nerves, the spinal cord, and the brain. It is a complex and controversial topic, yet current research and study is shedding more and more light on neural ideas such as cortical plasticity and body schema. Further exploration of this topic is a great way for the Neurophysiology students to strengthen their fundamental knowledge of the neurosystems, as well as engage in creative thought and imagination, as is demonstrated through Dr. Ramachandran's innovative mirror box! Phantom pain is an excellent reminder that, though the human knowledge of the brain is vast, there is plenty left to explore.

**Key Terms**

Phantom pain: squeezing, throbbing, or burning pain experienced in a limb that has been amputated Neuroma: a tumor growing on nerve tissue. Somatosensory cortex: area of the human brain located on the postcentral gyrus of the parietal lobe that receives sensory information from the bodies peripheral receptors. Homunculus: a visual representation portraying the designation of specific body parts to particular areas of the somatosensory cortex. Also termed "the body within the brain." ** Neuromatrix theory : the idea that the thalamus, the limbic system, and the cortex make up an integrated processing system that contribute to conscious awareness of body image. Body schema/image: the mental representation of the body Mirror box:** device used as physical rehabilitation for patients with phantom pain that allows the patient to view a reflection of their real arm in the visual space occupied by the phantom arm.
 * Phantom sensation**: painless feelings of tingling, temperature, or itching experienced in a limb that ** has been amputated.
 * Plasticity:** ** characteristic of the cortex that allows for "remapping," either through the growth of new synapses or the unmasking of non-prominent synapses.

**Suggested Readings and Links**

1. //Phantoms in the Brain// by V.S. Ramachandran and Sandra Blakeslee This book is an entertaining and educational read that incorporates a large variety of phantom patients and scenarios. 2. //The Man Who Mistook His Wife for a Hat// by Oliver Sacks Similar to Ramachandran's book, this is a compilation of case studies of patients who experienced a variety of phantom sensations. 3. [|End the Pain Project] http://endthepainproject.org/toolkit.html This website contains information on how to make and use a mirror box. 4. [|Treating "Phantom Limb Pain" with Mirror Box Therapy] http://www.youtube.com/watch?v=YL_6OMPywnQ This Youtube video shows Bryan Wagner, an amputee patient from the war in Iraq, being treated with mirror box therapy.

**Quiz**

__Multiple Choice__: 1. Neuromas that contribute to phantom pain are located a) in the thalamus b) on frayed nerve endings c) in the neuromatrix d) primarily in the spinal cord

2. It is sometimes the case for phantom pain that fibers from the dorsal column in the spinal cord have sprouted into a) the dorsal gray matter b) the dorsal root ganglion c) the spinocerebellar pathway d) the anterolateral pathway

3. Which one of these structures is not included in the neuromatrix? a) thalamus b) amygdala c) sensorimotor cortex d) none of the above

4. Which one of the following is not a surgical procedure associated with phantom pain? a) phlebotomy b) cordotomy c) dorsal rhizotomy d) removal of neuroma

__True/False__ 5. Phantom sensation and phantom pain are virtually interchangeable terms with the same definition. 6. Phantom pain experienced by the amputee patient tends to resemble pain experienced in the limb prior to amputation. 7. Mirror box therapy is more successful in treating phantom pain than surgery. 8. It is uncommon for amputee patients to have experiences with phantom pain.

__Short Answer__: 1. What is cortical plasticity and how does it contribute to phantom pain? 2. Sketch a diagram of the mirror box and describe the mechanisms behind its use. 3. List out the various anatomical structures that are affected by phantom pain.

ANSWERS:

1. B 2. D 3. D 4. A 5. False 6. True 7. True 8. False

**References**


 * 1**. Bittar RG, Otero S, Carter H, Aziz TZ. Deep brain stimulation for phantom limb pain. //Journal of Clinical Neuroscience// 12(4): 399–404.
 * 2**. Casale R, Alaa L, Mallick M, Ring H. Phantom limb related phenomena and their rehabilitation after lower limb aputation. //Eur J Phys Rehab MED// 45: 559-66, 2009.
 * 3**. 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// 6531: 482-484.
 * 4**. Lotze M, Flor H, Grodd W, Larbig W, Birbaumer N. Phantom movements and pain an fmri study in upper limb amputees. //Brain// 124(11): 2268-2277.
 * 5**. Mayo Clinic staff. (Nov 10, 2009). Phantom Pain [Online]. Mayo Clinic. http://www.mayoclinic.com/health/phantom-pain/ds00444 [5/04/10]
 * 6**. Moseley, GL, Brugger P. Interdependence of movement and anatomy persists when amputees learn a physiologically impossible movement of their phantom limb. //PNAS// doi: 10.1073/pnas.0907151106.
 * 7**. Ramachandran VS, Blakeslee S. //Phantoms in the brain: probing the mysteries of the human mind//. New York, NY: William Morrow and Company, Inc, 1998.
 * 8.** Sherman RA. (1997). Phantom limb pain: the use of electromyographic and temperature biofeedback for treatment of cramping and burning phantom limb pain. [Online].Biofeedback Foundation of Europe. http://www.bfe.org/protocol/pro05eng1.htm