Up to 90% of amputees experience phantom limb pain, sensations in the missing limb that patients may describe as burning, cramping, tingling, itching, stabbing, throbbing, or a feeling of “pins and needles.”1 Although in most individuals who experience phantom limb pain sensations are mild and intermittent, in some amputees, pain can be severe, chronic, and disabling.2
In the mid-20th century, psychological explanations for phantom limb pain were prevalent, with 1 highly cited 1973 article suggesting that emotional repression caused the persistence of painful phantom limbs, and that phantom limb pain might be prevented if patients were encouraged to fully express their feelings of grief, anger, and helplessness.3 Today, phantom limb pain is widely believed to have a neurological etiology. Phantom limb pain researcher Jack Tsao, MD, DPhil, from the University of Tennessee Health Science Center in Memphis, told Clinical Pain Advisor, “Neuroplasticity, or formation of novel neuronal connections between parts of the brain which were not previously connected; a dissociation between vision and proprioception (the sense of limb in space); and proprioceptive memories (memories of positions of the limb) are the most prominent theories [for mechanisms underlying limb pain]. Recent evidence suggests that there is an interaction between the peripheral nervous system and the brain, which can lead to the formation of phantom limb pain.”
In a recent review of findings on the psychological factors modulating phantom limb pain, Xaver Fuchs, PhD, from Bielefeld University, Germany, and colleagues concluded that emotional factors may act as contributors to phantom limb pain, but appear to play a smaller part compared with other types of chronic pain. “Compared to other types of pain, there has been little research on the role of psychological variables in [phantom limb pain]. [W]hether psychological variables are less important for [phantom limb pain] or whether they have merely been neglected needs to be determined in future studies that take emotional, motivational, perceptual, and cognitive variables into account,” concluded the authors of the review.4 Psychological dysfunctions, particularly depression and anxiety, are highly prevalent in patients with other types of chronic pain. Depression and anxiety in patients with chronic pain contribute to high levels of pain-related reactivity and altered connectivity, leading to reduced pain thresholds. Neuroinflammation is thought to be a common mediator of this comorbidity.5
In 2005, an estimated 1.6 million people in the United States underwent limb amputations, a number that is projected to increase to 3.6 million by 2050.6 Despite the significant population of patients potentially affected by phantom limb pain, clinical trials evaluating treatments for this condition have been scarce and have involved small cohorts. A Cochrane review published in 2011 and updated in 2016 on the evidence base for pharmacologic interventions in patients with established phantom limb pain identified 14 relevant randomized or quasi-randomized trials in clinical databases, with an aggregate total of only 269 participants. The review authors concluded that the effectiveness on pain, function, mood, sleep, quality of life, and satisfaction related with phantom limb pain of agents ranging from botulinum toxin A, opioids, N-methyl D-aspartate (NMDA) receptor antagonists (eg, ketamine, memantine, dextromethorphan), anticonvulsants, and antidepressants to calcitonin and local anesthetics was unclear.7,8 Information from the included trials was insufficient to support any particular pharmacologic treatment for phantom limb pain. Results of a nationwide survey of 537 amputees revealed that the vast majority of patients with phantom limb pain remain untreated.9
In a review examining a number of nonpharmacologic treatments for phantom limb pain (ie, electrotherapy, cognitive behavioral therapy, mirror therapy, sensory discrimination training, hypnotherapy, limb covers, biofeedback, reflexology, guided imagery, acupuncture, virtual reality, and prosthesis use and training), the authors concluded: “[T]here is a paucity of high-quality evidence upon which to make any firm clinical conclusions.”10 The investigators identified only 1 high-quality randomized controlled trial on the topic.
Mirror therapy, 1 of the more widely studied nonpharmacologic modalities for phantom limb pain, involves the strategic placement of mirrors to reflect the patient’s intact limb so that it appears superimposed over the phantom limb, thereby producing the illusion that the missing limb is present and can be moved normally.11 A systematic review of the medical literature on the effects of mirror therapy on pain and motor control of phantom limb in amputees found insufficient evidence to support its use as a first-intention treatment.12 Dr Tsao, who coauthored a recent retrospective study using data from 2 independent cohorts with unilateral lower limb amputation to determine the nature of pain symptoms that respond to mirror therapy (if any), told Clinical Pain Advisor, “We looked at our data and realized that, with more severe pain, more treatment sessions are necessary, whereas amputees with less severe pain should see an effect sooner if they are to respond to mirror therapy. Not everyone gets benefit from mirror therapy, but a great many do obtain pain relief. One area of research interest is why mirror therapy isn’t universally beneficial and what separates those who benefit from mirror therapy from those who don’t.”
- Katz J, Fashler S. Phantom limbs. In: Wright JD, ed. International Encyclopedia of the Social & Behavioral Sciences (Second Edition). Oxford: Elsevier; 2015:1-5.
- Nikolajsen L, Christensen KF. Chapter 2 – phantom limb pain. In: Tubbs RS, Rizk E, Shoja MM, Loukas M, Barbaro N, Spinner RJ, eds. Nerves and Nerve Injuries. San Diego: Academic Press; 2015:23-34.
- Parkes CM. Factors determining the persistence of phantom pain in the amputee. J Psychosom Res. 1973;17(2):97-108.
- Fuchs X, Flor H, Bekrater-Bodmann R. Psychological factors associated with phantom limb pain: a review of recent findings. Pain Res Manag. 2018;2018:5080123.
- Katz J, Rosenbloom BN, Fashler S. Chronic pain, psychopathology, and DSM-5 somatic symptom disorder. Can J Psychiatry. 2015;60:160-167.
- Ziegler-Graham K, MacKenzie EJ, Ephraim PL, Travison TG, Brookmeyer R. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil. 2008;89:422-429.
- Alviar MJM, Hale T, Dungca M. Pharmacologic interventions for treating phantom limb pain. Cochrane Database Syst Rev. 2011;12:CD006380.
- Alviar MJM, Hale T, Dungca M. Pharmacologic interventions for treating phantom limb pain. Cochrane Database Syst Rev. 2016;10:CD006380.
- Kern U, Busch V, Müller R, Kohl M, Birklein F. Phantom limb pain in daily practice–still a lot of work to do! Pain Med. 2012;13:1611-1626.
- Batsford S, Ryan CG, Martin DJ. Non-pharmacological conservative therapy for phantom limb pain: A systematic review of randomized controlled trials. Physiotherapy Theory and Practice. 2017;33:173-183.
- Ramachandran VS, Rogers-Ramachandran D. Synaesthesia in phantom limbs induced with mirrors. Proc Biol Sci. 1996;263(1369):377-386.
- Barbin J, Seetha V, Casillas JM, Paysant J, Pérennou D. The effects of mirror therapy on pain and motor control of phantom limb in amputees: A systematic review. Ann Phys Rehabil Med. 2016;59(4):270-275.
- Griffin SC, Curran S, Chan AWY, et al. Trajectory of phantom limb pain relief using mirror therapy: Retrospective analysis of two studies. Scand J Pain. 2017;15:98-103. doi:10.1016/j.sjpain.2017.01.007
- Andoh J, Milde C, Tsao JW, Flor H. Cortical plasticity as a basis of phantom limb pain: Fact or fiction? [published online November 16, 2018]. Neuroscience. doi:10.1016/j.neuroscience.2017.11.015