Phantom+Sensations+and+Perceptions

toc Phantom sensation involves conscious perception and sensation of body parts that are no longer present. The most common phantom sensations are localized to upper and lower extremities 2. Phantom limb patients often experience perceptions of tactile sensation in the absence of external stimulation on the phantom limb 1. This subset of tactile hallucinations commonly involves sensory experiences of touch, pressure, temperature, vibration, and most prominently, pain 1,2,3 .Phantom limb pain is consciously experienced by 98% of individuals with amputations, spinal cord injury, deafferentation, and congenital limb deficiency 1. Phantom limb sensations that lack subsequent pain perception are thought to be an adaptive compensatory mechanism, whereas those invoking pain are considered maladaptive 1. Phantom limb pain is often described as a burning, tingling, throbbing or cramping sensation in the nonexistent limb 1,2. The source of phantom limb pain has been linked to maladaptive peripheral and central nervous system alterations in brain areas pertaining to perception and body awareness 1,2. Additional theories regarding the origin of pain in these hallucinatory limb sensations include [|body schema] and the neuromatrix theory 1. Phantom limb pain is speculated to be associated with the reorganization of regions in the primary [|somatosensory cortex], the [|thalamus], the [|insular cortex], the[| anterior cingulate cortex], as well as in the [|cerebellum] 1,2. Moreover, phantom limb sensations can induce a hallucinatory perception of movement in the nonexistent limb 3. Treatments for phantom limb sensations, as well as coinciding phantom limb pain,include pharmacological, non-pharmacological and surgical treatment options 2. The most promising results have been witnessed in mental imagery and mirror therapy treatment methods 2,3,4.

=** Phantom Limb Syndrome Epidemiology **=

Phantom limb describes the perception of tactile sensation or pain that is experienced in the limb that is no longer present. Phantom limb patients experience both sensory and motor activation in their phantom limb 3. This clinical phenomenon was first described about 450 years ago by Ambroise Pare, a military surgeon 5. However, it was not until two centuries later that the name “phantom limb” was created by Silas Weir Mitchell 5. Mitchell’s original conception was that phantom limb syndrome represented a sensory hallucination 5. The classification of hallucinations as a mental disorder lead to early beliefs that the experience of a phantom limb may be a psychological problem in which the patient either experiences denial regarding the presence of their limb or experiences activation of memories about the phantom limb 5. But it was later determined that phantom limb patients do not suffer from a mental illness and they are fully aware that their limb is no longer present, even though they experience vivid phantom sensations 5.

It is estimated that 1.6 million individuals in the United States suffer from limb loss 2,6. The most common cause of limb loss is from amputation of the extremities 2. Amputation can occur as a result of trauma, spinal cord injury, tumor malignancy and inadequate blood flow 1,6. Phantom limb experiences can also occur in the absence of amputation and this is often associated with congenital limb deficiency 2.

Phantom sensations often appear instantaneously after amputation in 75% of patients; however the onset of these sensations can vary among patients and some may experience phantom limb sensations days, weeks or years after amputation 1,7. In some, the phantom sensation is only experienced for a short period but in others it may persist and have a longer duration 7. Phantom perceptions are experienced by 80% of patients with limb loss. These sensations include tingling, itching, twitching, gesturing, vibration, pressure, burning, cramping, piercing, hot and cold sensations and phantom limb pain 1,2,3,8. Many studies have found that phantom limb patients often perceive their phantom limb as resembling a functional intact limb, whereas some experience the perception of a telescoped or shrunken limb 9,10. Telescoping involves the perception that the proximal end of the limb is absent or shortened and that the digits or distal portion of the limb is situated close to or on the stump itself 8,9. Infrequently, patients can also experience the existence of a swollen or enlarged limb 3,8.

=** Phantom Limb Pain **=

Phantom sensations, following amputation, often result in the experience of residual stump pain and phantom limb pain 6. The incidence of phantom limb pain is estimated to be 50-80% in limb amputees 1,4. The most common types of phantom limb pain involve the sensation of cramping, tingling, piercing as well as sharp shooting pain 1,10.

The two common types of pain conditions that occur after amputation are residual stump pain and phantom limb pain. Residual stump pain is pain associated with the remaining parts of the upper or lower limbs after amputation, whereas phantom limb pain is associated with painful phantom limb perceptions 1.

Interestingly, it has been observed that phantom limb pain has an increased prevalence in patients with upper limb amputations compared to amputations of the lower extremities 1. The experience of phantom limb pain has also been reported to show gender differences and is more commonly observed in females than males 1. Phantom pain, following amputation, is often associated with abnormal posture including twists and bends into fixed unnatural positions 9,10.

=** Neurological Basis **=

The neurological basis of phantom limb pain involves a combination of many theories that have examined the pathophysiology of phantom limb sensations. Many mechanisms have been proposed in order to explain the phenomenon of phantom limb pain. The neurological basis of phantom limb pain is often related to changes in the central and peripheral nervous systems 1,5. Peripheral, spinal and central mechanisms are believed to play an important role in the perception of phantom limb pain; however no theory single-handedly is able to explain the complex neurological basis of phantom limb sensations and perceptions 1. It is now believed that the pathophysiology of phantom limb pain is best explained by a multifactorial mechanism 5.

** Peripheral Mechanisms  ** Amputation results in many [|peripheral nervous system] changes and these changes are a result of severed peripheral nerves after amputation 1. The severing of peripheral nerves results in neuronal injury, tissue damage and impairment in afferent input to the [|spinal cord] 1,11. These disruptions in afferent connections are known as deafferentation 11. After deafferentation, the severed nerves begin to grow towards each other, in an attempt to reform connections, but instead form knots known as neruomas 11. [|Neuromas]are often associated with hyperexcitability and unpredictable discharges 1,11. This abnormal excitability in phantom limb pain is thought to be caused by the accumulation of sodium channels in the neuromas 11,12. This theory is supported by many studies examining the pain alleviating effects of substances that block sodium channels and remove neuromas. Spontaneous discharges from neuromas are often associated with pain, suggesting that peripheral mechanisms may play an important role in the etiology of phantom limb pain 1,11,12. A study by Borghi et al indicated that [|ropivacaine], a sodium channel blocker, abates pain that is associated with the phantom limb. Neuroma removal has also been found to reduce phantom pain in some patients 11. The theory of peripheral nervous system changes associated with phantom pain is one of the prominent theories in explaining the pathogenesis of phantom limb pain. However, peripheral nerve sprouting and neuroma formation is not instantaneous; therefore immediate onset of phantom limb pain cannot be explained solely by [|peripheral nervous system] changes 1,11,13. In addition to peripheral mechanisms, other mechanisms may play an important role in patients who experience immediate onset of phantom limb pain.

** Spinal Cord Mechanisms **
After nerve damage, axonal sprouts from damaged peripheral nerves form connections with the spinal cord 2. Spinal cord neurons can also extend into the [|dorsal horn] and [|dorsal root ganglion] of the spinal cord, which contain sensory neurons that produce ectopic impulses 1 1. Neuronal activity in regions important for [|nociceptive] input transmission results in the summation of signals and an increase in nociceptive input, which is called central [|sensitization] 2. Inhibitory [|neurotransmitters], such as [|GABA] or [|glycine], could result in spinal disinhibition 11. It has also been determined that [|interneurons] can be damaged by nerve [|axotomy] and hyperexcitability 11,9. Nerve tissue damage can also result in an increase in NMDA receptor reactivity, at the level of the dorsal horn, in response to [|glutamate] 2,11. This mechanism disrupts the firing pattern of neurons that project from the spinal cord to various cortical areas 1,2,11. Studies examining the effect of spinal cord alterations on phantom limb pain have observed that tissue damage and injury result in the expression of [| substance P] on fibers that transmit proprioceptive information 11. Substance P is often associated with nociceptive stimuli; therefore fibers that, originally, did not transmit nociceptive info now may have the ability to transmit noxious information in phantom limb patients 11.

** Central Cerebral Mechanisms **
[|Central nervous system]changes in cortical regions are often considered to be the main underlying mechanism of phantom limb pain 1,2. Phantom limb pain has been connected to changes in many regions of the brain, including the anterior cingulate cortex, [|brainstem], thalamus and, most importantly, the primary somatosensory cortex and the [|primary motor cortex] 2,11,15. Often these cortical changes are associated with cortical reorganization in the brain 15. The cortical reorganization may be a result of axonal sprouting 11. Axonal sprouting is thought to be caused by increased excitability, which is a result of increased presence of excitatory neurotransmitter 2,11. Increased excitability in various cortical regions can lead to the experience of phantom limb pain 11. It has also been suggested that inhibitory fibers are lost due to amputation and this loss may cause cortical reorganization in areas where [|c-fibers] usually have an inhibitory effect 11. Cortical reorganization is often observed in areas that are associated with the sensory and motor homunculus 1,2,11,15. These cortical changes are often due to maladaptive plasticity, which results in phantom limb pain in many amputees 15. The somatosensory cortex displays the most amount of reorganization, and regions adjacent to the lost limb begin to occupy the somatosensory area that was once linked to the phantom limb 11,15. These maladaptive neural changes are thought to alter the body schema, which results in the experience of phantom sensations 11. Studies have also indicated that the [|cuneate nucleus] of the brainstem and the ventral posterior nuclei of the thalamus show a great deal of restructuring in areas associated with the face and lost limb 16. Therefore, the brainstem and thalamus may contribute to changes in body representation in the [|cortical homunculus].



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=** Theories of Phantom Limb Pain **=

** Neuromatrix Theory **
The neuromatrix or neurosigniture theory of phantom limb pain was first established by Ronald Melzack and this theory is closely related to the body schema concept 2. The neuromatrix is a neural network that produces different impulse patterns depending upon the input received from various cortical areas and the connections that are formed between different neural circuits 5. These cortical inputs are received from thalamocortical circuits, [|reticular formation]/limbic system circuits, visual areas and the somatosensory cortex 2,5. Inputs from these areas are processed and synthesized to form a characteristic, integrated output 5,17. The neuromatrix theory proposes that outputs, or nerve impulses, generated from cortical inputs from the self body schema form the basis of self awareness 5. The integrated output is classified as the neurosigniture and is thought to be hardwired 5,17. A hardwired neurosigniture may create problems after amputation because of conflict between perceptions regarding the post operational state of the body 2,5. The static neurosigniture cannot be altered after amputation even thought there is input indicating that the phantom limb is no longer present 5. The differences in input from the neurosigniture and the body gives rise to an overriding response that results in the perception that the body is still unchanged 5. The perception of an intact limb, regardless of contrary sensory input from the body, may be the underlying cause of phantom sensation and phantom limb pain 1,2,5.

** Cortical Reorganization Theory **
Cortical Reorganization theory is one of the most cited theories explaining the etiology of phantom limb pain 1,2. Merzerich et al examined the validity of the cortical reorganization theory and found that following amputation and deafferentation, adult monkeys displayed cortical changes in the somatosensory homunculus 14. Theses finding lead to the belief that cortical reorganization may be a key component in producing phantom limb sensations 7,15. Cortical reorganization theory suggests that maladaptive cortical reorganization occurs in the [|somatosensory cortex (S1)], as well as the [|motor cortex (M1)] 8. Maladaptive reorganization occurs when surrounding areas take over control of the somatosensory and motor representations of the missing limb 2,15. During cortical reorganization it is observed that regions of the face, often, take over homunculi regions associated with the arm in upper limb amputees 2,11,15. It is proposed that maladaptive plasticity and cortical reorganization in phantom limb patients explains the cause of phantom limb pain 15. [|Functional magnetic resonance imaging] data illustrates that patients who experience phantom limb pain have greater activation in somatosensory and motor cortices, where as amputees without pain and healthy controls show no increase in activation (Figure 4) 15. The strong support for the cortical reorganization theory has lead to the development of possible treatment methods that attempt to decrease the maladaptive cortical reorganization in amputees 2.





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=** Treatments **=

Treatments for phantom limb pain involve different techniques that focus on the various mechanisms associated with phantom limb pain 2. Primary intervention strategies include pharmacological treatments and non-pharmacological, behavioural treatments 2,9. Surgical treatment interventions have also been utilized; however they are rarely effective in alleviating phantom limb pain and are mainly administered when other treatment methods have failed to yield effective results 2,9.

** Pharmacological Treatments **
Various pharmacological treatment methods have been employed to treat phantom limb pain but effective techniques that completely alleviate symptoms are yet to be determined 18. Phantom limb pain is often difficult to treat due to its pathophysiology, which involves central and peripheral nervous system changes 2. Therefore, conventional treatment methods have little effect on pain reduction 19. Possible pharmacological treatment approaches include the use of pre-emptive analgesia and anaesthesia, opiods, NMDA receptor antagonists and Botulinum toxin type A 2,19,20,21.

** Pre-Emptive Analgesia and Anaesthesia **
Pre-emptive analgesia and [|anaesthesia]refers to the use of analgesics and anaesthetics before the amputation of the limb takes place 2. Experimental studies have observed that the administration of pre-emptive analgesia prevents [|hyperplasia]and neural sensitization that may result from stimuli associated with the amputated limb 2. These preventative measures in turn regulate and decrease future activation of painful stimuli associated with the phantom limb. Double blind studies, examining the effects of [|ketamine]and [|bupivacaine]administration, found that preoperative, analgesic injection into the [|epidural space] resulted in a decrease in phantom limb pain 2,22. Although pre-emptive analgesia administration helps control phantom limb pain directly after the amputation, the results are not conclusive and pre-emptive pharmacological treatment does not result in long term reduction of phantom limb pain and residual stump pain 2,5,23.

** Opiods **
[|Opioid]medication is often used to treat phantom limb pain. Opioids are chemicals that bind to central and peripheral nervous system opioid receptors. Huse et al observed the analgesic properties of morphine administration in patients experiencing severe phantom limb pain. It was observed that morphine sulphate treatment resulted in a 50% decrease in phantom limb pain experience in about half of the patients. [|Morphine]was also shown to play a role in the reduction of maladaptive cortical reorganization that is observed in phantom limb patients who experience severe pain 20. The etiology of phantom limb pain is often linked to cortical reorganization; therefore opioids could effectively treat phantom limb pain through mechanisms of action that disrupt cortical reorganization in the somatosensory and motor cortex 2,20. Although opioids may successfully treat phantom limb pain and decrease maladaptive cortical plasticity, several studies have shown that opioid administration is often associated with greater side effects 2,11. Common side effects include drowsiness, dizziness, nausea sweating and [|vertigo] 5 ,20. Opioid medication remains a common treatment method for neuropathic pain conditions, like phantom limb pain, however studies are not completely conclusive and fail to show an effect in some patients with severe phantom limb pain 20.

** NMDA Receptor Antagonist **
[|N-Methyl-D-aspartic acid] (NMDA) receptor antagonists, like [|Memantine], have been shown to decrease phantom limb pain in many patients and reverse cortical reorganization 21. NMDA receptors are thought to be associated with central and peripheral sensitization, which is predicted to be a result of increased [|glutamate]release during and after the injury 2,18. Administration of Memantine has been shown to decrease pain in some phantom limb patients, however the results are not definitive and various studies have obtained contradictory results 2,21. Hacksworth et al determined that Memantine is more effective than first generation NMDA receptor antagonists (Ketamine) 21. First generation NMDA receptor antagonists give rise to many side effects, including headaches, nausea, dizziness and more severe side effects such as loss of consciousness, decreased hearing, and perception of visual hallucinations 21. Lastly, studies have demonstrated that NMDA receptor antagonists may be effective as an initial treatment method, as opposed to a long term treatment strategy for alleviating phantom limb pain 2,11.

** Botulinum Toxin Type A **
[|Botulinum toxin] is a powerful neurotoxin produced by the bacterium [|Clostridium Botulinum] 24. Once internalized, Botulinum toxin type A inhibits [|acetylcholine]release from nerve endings by disrupting mechanisms involved in vesicle docking 24. These characteristics allow Botulinum toxin type A to be used in treatment of disorders associated with muscle contraction and various pain syndromes 24. Jin et al showed that phantom limb pain and stump pain were successfully treated and pain was reduced after administration of Botulinum toxin type A. This demonstrates that botulinum toxin may provide an addition technique that can be utilized to effectively treat phantom limb pain.

** Mirror Therapy **
====== Mirror therapy techniques that are used to treat phantom limb pain make use of visual feedback mechanisms and [|mirror neuron systems], which play an important role in goal directed behaviour 2. Phantom sensations, in amputees, often involve mirror neuron systems. It is thought that phantom limb patients experience mirror neuron activity when phantom limb perceptions are experienced as the patient observes the movement of others around them 2. It is thought that mirror neuron activity may reinforce the body schema concept and reinforce representation of the phantom limb within the cortex 2,11,25. Therefore, phantom limb perception may be due to the maintenance of limb representation within the cortex. Mirror neuron systems have also been implicated to play a role in touch and pain 2. Mirrored sensations are also observed in about 13% of phantom patients 2. These sensations involve mirrored perceptions from the intact limb to the phantom limb 2. These sensations include [|thermoception], [|tactition], [|proprioception]and nociception 2,25. Therefore it is proposed that mirror neuron systems involvement in tactile sensation and pain may reinforce and maintain the representation of the phantom in the cortex 2. This mirror neuron system and the cortical representation of the phantom limb are manipulated in treatment methods involving mirror therapy 25.

Ramachandran was the first to report the effectiveness of mirror therapy and visual feedback in the treatment of phantom limb pain 2. Patients observe movements of the intact limb in mirrors placed between the phantom limb and the intact limb. The visual feedback and reflection of the intact limb replaces the phantom limb 2,25. Mirror neurons systems in the brain show activation as sensations in the phantom limb are perceived from tactile stimuli associated with the mirrored reflection 2. Activation of mirror neurons in patients with amputated limbs results in tactile sensation without the presence of a real tactile stimulus on the phantom limb. Mirror therapy is thought  to modulate somatosensory input and as a result this modulation may decrease the perception of phantom limb pain and alleviate painful   phantom symptoms 2,25. Rehabilitation methods using the mirror box are mind-body therapies that are effective in treating phantom pain for many patients but these therapies do not alleviate pain in all phantom limb patients 2,26. A study by Diers et al looked at the effectiveness of mirror therapy treatment in patients suffering from severe phantom limb pain. They determined that mirror therapy does not show a significant effect in reducing phantom limb pain and it may not be the best form of treatment for patients with severe phantom limb pain 2,26. Instead, mirror imagery was found to be effective in alleviating some symptoms in patients with severe pain 26. During imagined movements there was no increase in cortical activity in areas that often showed cortical reorganization 26. Although the mechanisms are unclear, these experimental findings suggest that mirror imagery may also be an effective treatment for alleviating the painful symptoms experienced by phantom limb patients.

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**See Also**

[|Phantoms In the Brain Part 1 Episode 1] [|Phantoms In the Brain Part 2 Episode 1] [|Phantoms In the Brain Part 3 Episode 1] [|Phantoms In the Brain Part 4 Episode 1] [|Phantoms In the Brain Part 5 Episode 1]


 * References **


 * 1) Giummarra, M. J., Gibson, S. J., Georgiou-Karistianis, N, & Bradshaw, J. L. Central mechanisms in phantom limb perception: The past,present and future. //Brain Research Reviews// **54**, 219-232 (2007)
 * 2) Subedi, B. & Grossberg, G. T. Phantom limb pain: mechanisms and treatment approaches. // Pain Research and Treatment //** 1 **, 1-8 (2011)
 * 3) Raffin, E., Mattout, J., Reilly, K. T, & Giraux, P. Disentangling motor execution from motor imagery with the phantom limb. // Brain // **135**, 582–595 (2012)
 * 4) Diers, M., Christman, C., Koeppe, C., Ruf, M., & Flor, H. Mirrored, imagined and executed movements differentially activate sensorimotor cortex in amputees with and without phantom limb pain. // Pain //** 149 **, 296–304 (2010)
 * 5) Reilly, K. T, & Sirigu, A. The motor cortex and its role in phantom limb phenomena. // Neuroscientist //** 14 **, 195-202 (2008)
 * 6) Moura, V. L., Faurot, K. R., Gaylord, S. A., Mann, J. D., Sill, M., Lynch, C., & Lee, M.Y. Mind-body interventions for treatment of phantom limb pain in persons with amputation. //American J. Phys. Med. Rehabil//. **91**, 2-14 (2012)
 * 7) Ramachandran, V. S., & Hirstein, W. The perception of phantom limbs. //Brain// **121**, 1603-1630 (1998)
 * 8) Sumitani, M., Miyauchi, S., Yozu, A.,Otake, Y., Saitoh, Y., & Yamada, Y. Phantom limb pain in the primary motor cortex. // J Anesth // **24**, 337–341 (2010)
 * 9) Giummarra, M. J., & Moseley, G. L. Phantom limb pain and bodily awareness: current concepts and future directions. //Current Opinion in// Anesthesiology ** 24 **, 524–531 (2011)
 * 10) Giummarra, M. J., Georgiou-Karistianis, N., Nicholls, M. E. R., Gibson, S. J., Chou, M., & Bradshaw, J. L. Corporeal awareness and proprioceptive sense of the phantom. // British Journal of Psychology // **101**, 791–808 (2010)
 * 11) Foell, J., Bekrater-Bodmann, R., Flor, H.,, & Cole, J. Phantom limb pain after lower limb trauma: origins and treatments. //The International Journal of Lower Extremity Wounds// **10**, 224–235 (2011)
 * 12) Borghi, B., D’Addabbo, M., White, P. F., Gallerani, P., Toccaceli, L., Raffaeli, W., Tognu, A., Fabbri, N., & Mercuri, M. The use of prolonged peripheral neural blockade after lower extremity amputation: the effect on symptoms associated with phantom limb syndrome. // Anesthesia //** 111 **, 1308-1315 (2010)
 * 13) Vase, L., ] Egsgaard, L. L., Nikolajsen, L., Svensson, P., Jensen, T. S., & Arendt-Nielsen, L. Pain catastrophizing and cortical responses in amputees with varying levels of phantom limb pain: a high-density EEG brain-mapping study. Exp Brain Res **1,** 1-11 (2012)
 * 14) Merzenich, M. M. // et al. // Somatosensory cortical map changes following digit amputation in adult monkeys. //The Journal of Comparative Neurology// **224**, 591-605 (1984)
 * 15) // Flor,H., Nikolajsen, L., & Jensen //, S. T. Phantom limb pain: a case of maladaptive CNS plasticity?. //Nature// **7**, 873-881 (2006)
 * 16) Jones, E. G. & Pons, T. P. Thalamic and brainstem contributions to large-scale plasticity of primate somatosensory cortex. // Science //** 282 **, 1121–1125 (1998)
 * 17) Melzack, R.Pain and the neuromatrix in the brain**.** // Journal of Dental Education // **35**, 1378-1382 (2001)
 * 18) Alviar, M., Hale, T., & Dungca, M.Pharmacologic interventions for treating phantom limb pain. Intervention **1**, 2-52 (2011)
 * 19) Hackworth, R. J., Tokarz, K. A., Fowler, I. M., Wallace, S. C., & Stedje-Larsen, E. T. Profound pain reduction after induction of Memantine treatment in two patients with severe phantom limb pain**.** Pain Medicine **107,** 1377-1379 (2008)
 * Wu, C. L. et al. Morphine versus Mexiletine for treatment of postamputation pain**.** // Anesthesiology // **109**(2), 289–296 (2008)
 * 1) Hackworth, R. J., Tokarz, K. A., Fowler, I. M., Wallace, S. C., & Stedje-Larsen, E. T. Profound pain reduction after induction of Memantine treatment in two patients with severe phantom limb pain**.** Pain Medicine **107,** 1377-1379 (2008)
 * 2) Wilson, J. A. Nimmo, A. F. Fleetwood-Walker, S. M., & Colvin, L. A. A randomised double blind trial of the effect of preemptive epidural ketamine on persistent pain after lower limb amputation. // Pain //, **131**, 108–118 (2008)
 * 3) Ypsilantis E, Tang TY. Preemptive analgesia for chronic limb pain after amputation for peripheral vascular disease: a systematic review. //Ann Vasc Surg//; **24**, 1139–1146 (2010)
 * 4) Jin, L. et al. Treatment of phantom limb pain with botulinum toxin type A. //Pain Medicine// **10**, 300-304 (2009)
 * 5) Lamont, K., Chin, M., & Kogan, M. Mirror box therapy: seeing is believing. //Explore// ** 7, ** 369-372 (2011)
 * 6) Diers, M., Christmann, C., Koeppe, C., Ruf, M., Flor, H.Mirrored, imagined, and executed movements differentially activate sensorimotor cortex in amputees with and without phantom limb pain. //Pain// **149**(2), 296–304 (2010)