Introduction

Phantom limb pain (PLP) is a common post-amputation condition characterized by painful sensations in the missing limb. Approximately 80% of people report PLP within the first year following their amputation procedure, and up to 87% will experience PLP at some point in their lifetime.1 PLP is difficult to treat and contributes to the burden of physical disability, emotional well-being, and psychological disorders in people with amputations.2

Most pharmacological treatments for PLP are based on limited evidence and do not offer benefits over placebo.3–5 On the other hand, a few non-pharmacological treatments are showing some benefit, with mirror therapy being one of the most widely employed treatments. For example, recent meta-analyses revealed that mirror therapy was more effective than control interventions,6,7 however, contradictory findings have also been reported, highlighting the need for further analysis.8,9 Additionally, in a study that generated treatment recommendations for PLP, mirror therapy had the highest level of expert consensus for its efficacy in reducing PLP.10 Despite mirror therapy appearing to be the gold standard for PLP management amongst healthcare professionals, a standardized treatment protocol is yet to be established to facilitate rigorous testing of the effectiveness of mirror therapy between groups.

There are several discrepancies in how mirror therapy is conducted in clinical practice. Most notably, inconsistencies exist in its application (for instance, moving vs resting the phantom limb), the method of delivery (ie, self-guided vs clinician-led), and the number, duration, and frequency of treatment sessions.11 We hypothesized that variations in mirror therapy protocols are the source of conflicting results, and perhaps developing a standardized treatment protocol could address this aspect of clinical heterogeneity.

A standardized treatment protocol may enhance the reliability and reproducibility of treatment outcomes in future studies and ensure a meaningful comparison between mirror therapy and other treatments in clinical trials and meta-analyses. In consideration of this, we conducted this study to evaluate how mirror therapy is performed and reported in the literature on PLP. In addition, we aimed to identify treatment features unique to studies with clinically significant pain outcomes. These features will inform the development of a standardized mirror therapy protocol in an ongoing expert consensus Delphi study.

Materials and Methods

This scoping review was conducted in accordance with the Joanna Briggs Institute (JBI) manual for evidence synthesis12 and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines (PRISMA-ScR).13 The protocol for this review has been registered on Open Science Framework.14

Identification of Studies

We used a customized search strategy (Supplementary file 1) to search for relevant studies across the following databases: Medline (via EBSCOhost), PubMed, Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database, PsycINFO (via EBSCOhost), Cumulative Index to Nursing and Allied Health Literature (via EBSCOhost), Africa-Wide Information (via EBSCOhost), and Scopus. In addition, we searched clinicaltrials.gov, Pactr.gov, and the European Union clinical trials register for ongoing research. Electronic databases and clinical registries were searched from their inception until July 2024.

Eligibility Criteria

We considered clinical studies which investigated the efficacy of mirror therapy for reducing PLP in adults (≥18 years) with an amputation of the upper or lower limb. We only considered studies published in English due to a lack of translation resources. Systematic reviews and retrospective analyses of previously published data were excluded to avoid duplication.

Screening and Study Selection

Two reviewers (K.L. and E.M) independently screened titles and abstracts of studies identified from the literature search in duplicate. Eligible full-text articles were retrieved and screened independently by the reviewers to confirm inclusion. Where additional information was required to confirm eligibility, K.L. contacted authors up to two times within two weeks for clarification. Disagreements between reviewers were resolved by discussion. We calculated Cohen’s kappa to determine inter-rater agreement as minimal (0–0.39), weak (0.40–0.59), substantial (0.60–0.79), or strong (0.80–0.90).15

Data Extraction

Two reviewers (K.L. and E.M) independently extracted data from included studies using a piloted, customized form. Extracted data included study characteristics (ie, design and setting), treatment characteristics (details of pre-mirror therapy participant education, treatment technique, types of limb exercises, duration and frequency of treatment sessions, and overall treatment period), and treatment efficacy. Treatment efficacy was judged as either “effective” or “not effective”, depending on whether the study achieved a clinically meaningful reduction in pain, defined as at least a 50% reduction or a 2-point decrease on a 0–10 numerical rating scale.16,17 We reviewed extracted data and identified common treatment features across studies with clinically significant pain outcomes. Disagreements between reviewers were resolved by discussion.

Results

The screening process is illustrated in Figure 1. The literature search yielded 702 studies, from which, 233 were retained after de-duplication. Following the screening of titles and abstracts, 39 studies were deemed eligible for full-text review. Of these studies, 32 met our eligibility criteria and were included in this review. Fourteen studies are Randomized Controlled Trials (RCTs),18–31 11 are case studies,32–42 four are single-arm trials,43–46 two are prospective studies,47,48 and one is a non-randomized controlled trial.49 Additional characteristics of the included studies are summarized in Table 1. The screening of titles and abstracts and full-text articles reflected a substantial (0.64) and strong (0.84) inter-rater agreement, respectively. Mirror therapy was deemed “effective” in 21 studies for achieving a clinically meaningful reduction in pain. However, it was considered “ineffective” in 11 studies due to a lack of observed effect.

Figure 1 The PRISMA flow chart.

Table 1 Components of Mirror Therapy for PLP Management

Study Setting

Among the studies showing clinically meaningful pain reduction, 15 were conducted in a clinical setting,24–26,29,31,33–35,38–42,46,50 four were conducted both in a clinical environment and at home,18,47,49,51 and two were purely home-based.20,37 In contrast, among the studies showing no effect, seven were conducted both in a clinical setting and at home,21–23,27,32,36,43 three were conducted in a clinical setting,19,30,44 and one was home-based.48

Pre-Treatment Education

Among the studies showing clinically meaningful pain reduction, two provided both pain science education and instructions on the practical aspects of mirror therapy.20,37 In fifteen studies, only the instructions on the practical aspects of mirror therapy were provided,18,24,26,28,31,33–35,38–40,46,47,49,51 and four studies did not report any pre-treatment education.25,29,41,42 The clinicians did not demonstrate the exercises in 12 out of 21 studies.

Similarly, among studies showing no effect, one provided both pain science education and instructions on the practical aspects of mirror therapy.32 In nine studies, only the instructions on the practical aspects of mirror therapy were provided,19,21–23,27,30,43,44,48 and one study did not report pre-treatment education.36 The clinician did not demonstrate the exercises in seven out of 10 studies.

Treatment Technique

Among the studies showing clinically meaningful pain reduction, twelve involved synchronous movements of the phantom and intact limbs while viewing the reflection of the intact limb in the mirror.18,24,26,28,29,33–35,39,45,47,49 In two studies, the participants imagined moving the phantom limb,38,46 and in six studies, the participants did not move the phantom limb.20,25,37,40–42 One study did not report the technique used.29

Among studies showing no effect, seven involved synchronous movements of the phantom and intact limbs while viewing the reflection of the intact limb in the mirror.19,21–23,30,32,43 In one study, the participants imagined moving the phantom limb,44 and in three studies, the participants did not move the phantom limb.27,36,48

Exercises

Among the studies showing clinically meaningful pain reduction, fourteen involved clinician-guided mirror therapy exercises,20,26,28,29,31,33,35–37,40,41,45,47,49 and two involved self-guided exercises.42,46 Five studies did not report the method of exercise delivery.24,25,34,38,39 The majority of these studies focused on exercises involving both the simple movements of the affected joints and complex movements of distal joints.

Among studies showing no effect, eight involved clinician-guided mirror therapy exercises,19,21,22,30,32,36,43,44 and two studies involved self-guided exercises.23,48 One other study did not report the method of exercise delivery.27 Most of these studies focused on exercises involving simple movements of the affected joints.

Treatment Duration

Among the studies showing clinically significant pain reduction, nine had 15-minute treatment sessions.18,24,26,31,33–35,40,45 In seven studies, treatment sessions ranged between 20 and 30 minutes,25,28,29,37,38,47,49 and lasted for 1046 and 5 minutes20 in two individual studies. Three studies did not report the duration of treatment sessions.39,41,42

Among studies showing no effect, five had treatment sessions ranging between 20 and 30 minutes.21,27,32,36,48 In four studies, treatment sessions lasted 15 minutes,22,23,30,43 and for 10 minutes in one study.44 One study did not report the duration of treatment sessions.19

Treatment Frequency

Among the studies showing clinically significant pain reduction, eleven involved daily treatment sessions,18,20,24–26,33,34,39,45,46,49 and four involved one treatment session every weekday.29,31,35,38 One40 and two28,47 studies involved two and four treatment sessions per week, respectively. One study involved three treatment sessions per week.37 One study had a once-off session,42 and another did not report the frequency of treatment sessions.41

Among the studies showing no effect, seven studies involved daily treatment sessions,23,27,32,36,43,44,48 one study involved one treatment session every weekday,30 and another study involved a once-off treatment session.19 The frequency of treatment sessions was unclear in two studies.21,22

Treatment Period

Among the studies showing clinically significant pain reduction, ten had a treatment period of four weeks,18,20,24,26,31,35,37,38,49,51 and two had a treatment period of four days,25,34 two weeks,29,33 and three weeks,28,47 respectively. The five individual studies had a treatment period ranging from one day42 to two years.41

Among the studies showing no effect, seven had a treatment period of four weeks,21–23,30,32,43,48 two had a treatment period of one day,19,44 and one had a treatment period of 24 weeks.36 One other study did not report the treatment period.27

Discussion

This scoping review aimed to evaluate the application of mirror therapy across the literature and to identify treatment features unique to studies with clinically significant pain outcomes. Our findings revealed a wide variation in the application of mirror therapy across PLP studies. In addition, most of the treatment features were common in studies both with and without a clinically significant pain reduction. However, some differences were seen in features including the treatment setting, types of exercise, and treatment session duration.

Of the 32 studies included in this review, only 14 were RCTs, and were consistently judged in previous systematic reviews as having high risk of bias, stemming from inadequate participant blinding, and using a small sample size.6,7,11 These missing key features of high-quality trials could have had an impact on the imprecision of the effect estimates commonly seen in mirror therapy trials. Consequently, in a recent meta-analysis,11 the certainty of the evidence indicating the effectiveness of mirror therapy for reducing PLP was downgraded to “very low”. Nevertheless, the evidence on mirror therapy is promising, and it remains one of the most preferred options for clinicians to manage PLP.10 Therefore, it is imperative to refine its application and conduct high-quality, blinded RCTs with larger sample sizes to increase our confidence in mirror therapy as an effective treatment for PLP.

Most studies conducted in a clinical setting showed significant improvements in pain compared to home-based studies. Early studies were conducted in person, whereas more recent ones were conducted virtually, with substantial responsibility placed on the participant to manage and adhere to the treatment protocol.52 The sub-optimal treatment outcomes in home-based studies could be attributed to poor treatment adherence.53 A study by Nicholas et al54 revealed a negative association between adherence to self-management strategies and pain severity, in that the participants who adhered to the treatment protocol showed significantly greater improvement in pain compared to those who deviated from it. Monitoring adherence to treatment remains a significant challenge, particularly in home-based studies investigating non-pharmacological treatments such as mirror therapy. Virtual mirror therapy, utilizing digital technologies to deliver visual feedback, addresses some of the limitations of traditional mirror therapy, including the ability to monitor treatment adherence. The software employed in virtual mirror therapy has built-in capabilities for monitoring treatment duration and frequency, as well as the types of exercises performed during a treatment session.55 Therefore, utilizing digital technologies in clinical practice can improve treatment adherence, and thus treatment efficacy.

We noted important variations in the technique implemented across mirror therapy studies. While in some studies the participants moved the phantom limb, in other studies, they imagined moving or did not move the phantom limb while viewing the reflection of the intact limb in the mirror. Actively attempting to move the phantom limb has been hypothesized as a key feature for treatment success.56 A lack of a statistically significant difference in PLP severity in a meta-analysis comparing mirror therapy and sham (covered mirror) suggests that phantom motor execution, instead of visual feedback, is a key therapeutic component.11,57 Considering these findings, we found it surprising that clinically significant pain reductions were not unique to studies that prioritized phantom motor executions. This could be an artefact of methodological challenges unique to the application of mirror therapy in individuals with amputations. Unlike in individuals with limbs, it is difficult to confirm if movement of the phantom limb has been executed.58 Therefore, it is likely that some participants might have not executed phantom movements, hence the varying pain outcomes. Surface electromyography (sEMG) on the distal part of the residual limb has previously been used as a proxy measure for phantom movements, in that the contraction of the residual limb muscles suggests phantom movements.59 Along with other technological aids, such as machine learning on sEMG,60 virtual reality, and augmented reality have also been used to promote phantom motor execution.61

Complex phantom limb exercises during mirror therapy appear to play a significant role in pain alleviation. In this review, studies focusing on complex phantom exercises demonstrated greater efficacy compared to those focusing solely on simple joint movements. This is potentially because complex phantom limb movements, involving multiple joints and a range of motions, engage a wider network of neurons related to the control of the affected limb.56 For example, a mechanistic study comparing the effects of simple versus complex movements on corticospinal excitability found that complex movements led to higher corticospinal excitability.62 In addition, a recent study demonstrated that complex exercises resulted in better motor learning compared to simple exercises.63 However, given that complex mirror therapy exercises can trigger or aggravate pain in some patients, we recommend initiating treatment with simple exercises within a comfortable range of motion and gradually progressing to performing complex limb movements efficiently and fluidly.

We noted a high variability in treatment dosage across the included studies. However, a protocol comprising 15-minute daily sessions conducted over 4 weeks, was commonly seen across studies with positive pain outcomes. Although a consensus on the optimal dosage for MT is yet to be reached,64 it is known that individuals with chronic PLP tend to benefit from a longer treatment period, with those experiencing acute PLP of an early onset post-amputation, requiring only a few sessions to achieve significant pain reductions.18 It could be argued that a 15-minute treatment session is not sufficient to achieve a therapeutic effect. However, considering that excessive mirror training can aggravate pain or result in fatigue, stiffness, or spasms of the phantom limb, longer treatment sessions should be practiced with caution.65 Moreover, the evidence suggests that treatment frequency is more important than the duration of a treatment session.7 Nevertheless, the etiology of PLP varies significantly across individuals with limb amputations. Therefore, it is imperative to tailor treatment according to the clinical presentation of each individual.

It can be argued that there is an overrepresentation of studies with favorable outcomes, despite indications that mirror therapy outcomes in clinical practice sometimes fall short of the exceptional results often reported in the literature. This is likely due to several reasons, one of which is poor adherence in clinical practice versus prospective clinical studies. The lack of representation of studies with less favorable outcomes may be an artefact of publication bias, where studies with negative or neutral results are less likely to be published. This bias could distort our understanding of the factors that affect the efficacy of mirror therapy in reducing PLP. On the contrary, addressing this bias would help identify the factors that contribute to its success or limitations in reducing PLP, ultimately guiding more effective treatment strategies for individuals with limb amputations.

Conclusion

This review highlights common trends and inconsistencies in the practice of mirror therapy in people with limb amputations. Despite identifying common treatment features across studies with clinically significant pain outcomes, there remains a lack of a standardized mirror therapy protocol. Mirror therapy remains one of the most promising and preferred non-pharmacological treatments for PLP due to its ease of accessibility, adaptability to patient-specific complaints, and low cost. Establishing a standardized treatment protocol could enhance the reliability and reproducibility of treatment outcomes in future studies and ensure a meaningful comparison between mirror therapy and other treatments in future clinical trials and meta-analyses.

Disclosure

The authors report no conflicts of interest in this work.

References

1. Stankevicius A. Prevalence and incidence of phantom limb pain, phantom limb sensations and telescoping in amputees: a systematic rapid review. Eur J Pain. 2021;25(1):23–38. doi:10.1002/ejp.1657

2. 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. doi:10.1155/2018/5080123

3. Aternali A, Katz J. Recent advances in understanding and managing phantom limb pain. F1000Research. 2019;8:8. doi:10.12688/f1000research.17047.1

4. Erlenwein J. Clinical updates on phantom limb pain. Pain Rep. 2021;6(1):888. doi:10.1097/PR9.0000000000000888

5. Alviar MJ, Hale T, Dungca M. Pharmacologic interventions for treating phantom limb pain. Cochrane Database Syst Rev. 2016;10(10):006380.

6. Xie HM. Effectiveness of mirror therapy for Phantom limb pain: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2022;103(5):988–997. doi:10.1016/j.apmr.2021.07.810

7. Wang F. Effects of mirror therapy on phantom limb sensation and phantom limb pain in amputees: a systematic review and meta-analysis of randomized controlled trials. Clin Rehabil. 2021;35(12):1710–1721. doi:10.1177/02692155211027332

8. 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. doi:10.1016/j.rehab.2016.04.001

9. Rajendram C, Ken-Dror G, Han T, Sharma P. Efficacy of mirror therapy and virtual reality therapy in alleviating phantom limb pain: a meta-analysis and systematic review. BMJ Mil Health. 2022;168(2):173–177. doi:10.1136/bmjmilitary-2021-002018

10. Limakatso K, Parker R. Treatment recommendations for phantom limb pain in people with amputations: an expert consensus Delphi Study. Pm R. 2021;13(11):1216. doi:10.1002/pmrj.12556

11. Limakatso K. The efficacy of graded motor imagery and its components on phantom limb pain and disability: a systematic review and meta-analysis. Can J Pain. 2023;7:2188899. doi:10.1080/24740527.2023.2188899

12. Peters MD. Chapter 11: scoping reviews. JBI Man Evid Synth. 2020;169(7):467–473.

13. McGowan J. Reporting scoping reviews—PRISMA ScR extension. J Clin Epidemiol. 2020;123:177–179. doi:10.1016/j.jclinepi.2020.03.016

14. Limakatso K. Evaluating mirror therapy protocols in studies with clinically significant pain reductions.

15. Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Meas. 1960;20(1):37–46. doi:10.1177/001316446002000104

16. Martin WJ, Ashton-James C, Skorpil N, Heymans M, Forouzanfar T. What constitutes a clinically important pain reduction in patients after third molar surgery? Pain Res Manag J Can Pain Soc. 2013;18(6):319–322. doi:10.1155/2013/742468

17. Smith SM, Dworkin RH, Turk DC, et al. Interpretation of chronic pain clinical trial outcomes: IMMPACT recommended considerations. Pain. 2020;161(11):2446–2461. doi:10.1097/j.pain.0000000000001952

18. Anaforoğlu Külünkoğlu B, Erbahçeci F, Alkan A. A comparison of the effects of mirror therapy and phantom exercises on phantom limb pain. Turk J Med Sci. 2019;49(1):101–109. doi:10.3906/sag-1712-166

19. Brodie EE, Whyte A, Niven CA. Analgesia through the looking-glass? A randomized controlled trial investigating the effect of viewing a “virtual” limb upon phantom limb pain, sensation and movement. Eur J Pain. 2007;11(4):428–436. doi:10.1016/j.ejpain.2006.06.002

20. Ol HS. Mirror therapy for phantom limb and stump pain: a randomized controlled clinical trial in landmine amputees in Cambodia [with consumer summary. Scand J Pain. 2018;18(4):603–610. doi:10.1515/sjpain-2018-0042

21. Rothgangel A. Traditional and augmented reality mirror therapy for patients with chronic phantom limb pain (PACT study): results of a three-group, multicentre single-blind randomized controlled trial. Clin Rehabil. 2018;32(12):1591–1608. doi:10.1177/0269215518785948

22. Gunduz ME. Effects of combined and alone transcranial motor cortex stimulation and mirror therapy in phantom limb pain: a randomized factorial trial. Neurorehabil Neural Repair. 2021;35(8):704–716. doi:10.1177/15459683211017509

23. Zaheer A. Effects of phantom exercises on pain, mobility, and quality of life among lower limb amputees; a randomized controlled trial. BMC Neurol. 2021;21(1):1–8. doi:10.1186/s12883-021-02441-z

24. Chan BL. Mirror therapy for phantom limb pain. N Engl J Med. 2007;357(21):2206–2207. doi:10.1056/NEJMc071927

25. Tilak M. Mirror therapy and transcutaneous electrical nerve stimulation for management of phantom limb pain in amputees—a single blinded randomized controlled trial. Physiother Res Int. 2016;21(2):109–115. doi:10.1002/pri.1626

26. Ramadugu S. Intervention for phantom limb pain: a randomized single crossover study of mirror therapy. Indian J Psychiatry. 2017;59(4):457–464. doi:10.4103/psychiatry.IndianJPsychiatry_259_16

27. Mallik AK. Comparison of relative benefits of mirror therapy and mental imagery in phantom limb pain in amputee patients at a tertiary care center. Arch Rehabil Res Clin Transl. 2020;2(4):100081. doi:10.1016/j.arrct.2020.100081

28. Brunelli S. Is mirror therapy associated with progressive muscle relaxation more effective than mirror therapy alone in reducing phantom limb pain in patients with lower limb amputation? Int J Rehabil Res. 2023;46(2):193–198. doi:10.1097/MRR.0000000000000582

29. Segal N. Additive analgesic effect of transcranial direct current stimulation together with mirror therapy for the treatment of phantom pain. Pain Med. 2021;22(2):255–265. doi:10.1093/pm/pnaa388

30. Finn SB. A randomized, controlled trial of mirror therapy for upper extremity phantom limb pain in male amputees. Front Neurol. 2017;8:267. doi:10.3389/fneur.2017.00267

31. Noureen A. Effects of routine physical therapy with and without mirror therapy on phantom limb pain and psychosocial adjustment to amputation among prosthesis users. Physiother Q. 2022;30(2):8–14. doi:10.5114/pq.2021.108680

32. Yildirim M, Sen S. Mirror therapy in the management of phantom limb pain. AJN Am J Nurs. 2020;120(3):41–46. doi:10.1097/01.NAJ.0000656340.69704.9f

33. Wilcher DG, Chernev I, Yan K. Combined mirror visual and auditory feedback therapy for upper limb phantom pain: a case report. J Med Case Rep. 2011;5(1):41. doi:10.1186/1752-1947-5-41

34. Sae Young K, Young KY. Mirror therapy for phantom limb pain. Korean J Pain. 2012;25(4):272–274. doi:10.3344/kjp.2012.25.4.272

35. Gover-Chamlou A, Tsao JW. Telepain management of phantom limb pain using mirror therapy. Telemed J E-Health off J Am Telemed Assoc. 2016;22(2):176–179.

36. Clerici CA, Spreafico F, Cavallotti G. Mirror therapy for phantom limb pain in an adolescent cancer survivor. Tumori J. 2012;98(1):27–30. doi:10.1177/030089161209800134

37. Darnall BD. Self-delivered home-based mirror therapy for lower limb phantom pain. Am J Phys Med Rehabil Acad Physiatr. 2009;88(1):78. doi:10.1097/PHM.0b013e318191105b

38. Deng C, Li Q. Case report: a combination of mirror therapy and magnetic stimulation to the sacral plexus relieved phantom limb pain in a patient. Front Neurosci. 2023;17:1187486. doi:10.3389/fnins.2023.1187486

39. Datta R, Dhar M. Mirror therapy: an adjunct to conventional pharmacotherapy in phantom limb pain. J Anaesthesiol Clin Pharmacol. 2015;31(4):575–578. doi:10.4103/0970-9185.169102

40. Thomas S. Effectiveness of electromyographic biofeedback, mirror therapy, and tactile stimulation in decreasing chronic residual limb pain and phantom limb pain for a patient with a shoulder disarticulation: a case report. J Prosthet Orthot. 2015;27(2):68–76. doi:10.1097/JPO.0000000000000060

41. Folch A. Mirror therapy for phantom limb pain in moderate intellectual disability A case report. Eur J Pain. 2022;26:246–254. doi:10.1002/ejp.1859

42. Ramachandran V. Relief from intractable phantom pain by combining psilocybin and Mirror Visual-Feedback (MVF). Neurocase. 2018;24(2):105–110. doi:10.1080/13554794.2018.1468469

43. Foell J. Mirror therapy for phantom limb pain: brain changes and the role of body representation. Eur J Pain. 2014;18(5):729–739. doi:10.1002/j.1532-2149.2013.00433.x

44. Wareham AP, Sparkes V. Effect of one session of mirror therapy on phantom limb pain and recognition of limb laterality in military traumatic lower limb amputees: a pilot study. BMJ Mil Health. 2020;166(3):146–150. doi:10.1136/jramc-2018-001001

45. Houston H, Dickerson AE, Qiang W. Combining the absence of electromagnetic fields and mirror therapy to improve outcomes for persons with lower-limb vascular amputation. J Prosthet Orthot. 2016;28(4):154–164. doi:10.1097/JPO.0000000000000108

46. Sumitani M. Mirror visual feedback alleviates deafferentation pain, depending on qualitative aspects of the pain: a preliminary report. Rheumatology. 2008;47(7):1038–1043. doi:10.1093/rheumatology/ken170

47. Seidel S. Mirror therapy in lower limb amputees–a look beyond primary motor cortex reorganization. ROFO Fortschr Geb Rontgenstr. Nuklearmed. 2011;183(11):1051–1057.

48. Darnall BD, Li H. Home-based self-delivered mirror therapy for phantom pain: a pilot study. J Rehabil Med Stiftelsen Rehabiliteringsinformation. 2012;44(3):254–260. doi:10.2340/16501977-0933

49. Yıldırım M, Kanan N. The effect of mirror therapy on the management of phantom limb pain. Agri: agri (Algoloji) Dernegi’nin Yayin organidir. J Turk Soc Algol. 2016;28(3):127–134.

50. Brunelli S. Efficacy of progressive muscle relaxation, mental imagery, and phantom exercise training on phantom limb: a randomized controlled trial. Arch Phys Med Rehabil. 2015;96(2):181–187. doi:10.1016/j.apmr.2014.09.035

51. Houston H, Dickerson AE. Improving functional outcomes for vascular amputees through use of mirror therapy and elimination of the effects of electromagnetic fields. Occup Ther Health Care. 2016;30(1):1–15. doi:10.3109/07380577.2015.1060376

52. Betcheva L. Applying systems thinking to inform decentralized clinical trial planning and deployment. Ther Innov Regul Sci. 2023;57(5):1081–1098. doi:10.1007/s43441-023-00540-2

53. Timmerman L. Prevalence and determinants of medication non‐adherence in chronic pain patients: a systematic review. Acta Anaesthesiologica Scandinavica. 2016;60(4):416–431. doi:10.1111/aas.12697

54. Nicholas MK. Is adherence to pain self‐management strategies associated with improved pain, depression and disability in those with disabling chronic pain? Eur J Pain. 2012;16(1):93–104. doi:10.1016/j.ejpain.2011.06.005

55. Annaswamy TM. Clinical feasibility and preliminary outcomes of a novel mixed reality system to manage phantom pain: a pilot study. medRxiv. 2020;2020–2028.

56. Ortiz-Catalan M. The stochastic entanglement and phantom motor execution hypotheses: a theoretical framework for the origin and treatment of phantom limb pain. Front Neurol. 2018;9:748. doi:10.3389/fneur.2018.00748

57. Guémann M. Effect of mirror therapy in the treatment of phantom limb pain in amputees: a systematic review of randomized placebo‐controlled trials does not find any evidence of efficacy. Eur J Pain. 2022;27:3–13. doi:10.1002/ejp.2035

58. Raffin E, Giraux P, Reilly KT. The moving phantom: motor execution or motor imagery? Cortex. 2012;48(6):746–757. doi:10.1016/j.cortex.2011.02.003

59. Akbulut A. Identification of phantom movements with an ensemble learning approach. Comput Biol Med. 2022;150:106132. doi:10.1016/j.compbiomed.2022.106132

60. Ortiz-Catalan M, Sander N, Kristoffersen MB, Håkansson B, Brånemark R. Treatment of phantom limb pain (PLP) based on augmented reality and gaming controlled by myoelectric pattern recognition: a case study of a chronic PLP patient. Front Neurosci. 2014;8:24. doi:10.3389/fnins.2014.00024

61. Ortiz-Catalan M. Phantom motor execution facilitated by machine learning and augmented reality as treatment for phantom limb pain: a single group, clinical trial in patients with chronic intractable phantom limb pain. Lancet. 2016;388(10062):2885–2894. doi:10.1016/S0140-6736(16)31598-7

62. Roosink M, Zijdewind I. Corticospinal excitability during observation and imagery of simple and complex hand tasks: implications for motor rehabilitation. Behav Brain Res. 2010;213(1):35–41. doi:10.1016/j.bbr.2010.04.027

63. Heena N. Effects of task complexity or rate of motor imagery on motor learning in healthy young adults. Brain Behav. 2021;11(11):02122. doi:10.1002/brb3.2122

64. Hagenberg A, Carpenter C. Mirror visual feedback for phantom pain: international experience on modalities and adverse effects discussed by an expert panel: a delphi study. PM R. 2014;6(8):708–715. doi:10.1016/j.pmrj.2014.01.005

65. Rothgangel A. Development of a clinical framework for mirror therapy in patients with phantom limb pain: an evidence-based practice approach. Pain Pract. 2016;16(4):422–434. doi:10.1111/papr.12301