A Placebo-Controlled Randomized Crossover Trial of the N-Methyl-d-Aspartic Acid Receptor Antagonist, Memantine, in Patients with Chronic Phantom Limb Pain

ObjectiveTo determine whether training with a brain–computer interface (BCI) to control an image of a phantom hand, which moves based on cortical currents estimated from magnetoencephalographic signals, reduces phantom limb pain.MethodsTwelve patients with chronic phantom limb pain of the upper limb due to amputation or brachial plexus root avulsion participated in a randomized single-blinded crossover trial. Patients were trained to move the virtual hand image controlled by the BCI with a real decoder, which was constructed to classify intact hand movements from motor cortical currents, by moving their phantom hands for 3 days (“real training”). Pain was evaluated using a visual analogue scale (VAS) before and after training, and at follow-up for an additional 16 days. As a control, patients engaged in the training with the same hand image controlled by randomly changing values (“random training”). The 2 trainings were randomly assigned to the patients. This trial is registered at UMIN-CTR (UMIN000013608).ResultsVAS at day 4 was significantly reduced from the baseline after real training (mean [SD], 45.3 [24.2]–30.9 [20.6], 1/100 mm; p = 0.009 < 0.025), but not after random training (p = 0.047 > 0.025). Compared to VAS at day 1, VAS at days 4 and 8 was significantly reduced by 32% and 36%, respectively, after real training and was significantly lower than VAS after random training (p < 0.01).ConclusionThree-day training to move the hand images controlled by BCI significantly reduced pain for 1 week.Classification of evidenceThis study provides Class III evidence that BCI reduces phantom limb pain.

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The effect of electromagnetic shielding on phantom limb pain: A placebo-controlled double-blind crossover trial

Prosthetics and Orthotics International ◽

10.1177/0309364614568409 ◽

2015 ◽

Vol 40 (3) ◽

pp. 350-356 ◽

Cited By ~ 1

Author(s):

Keren Fisher ◽

Sarah Oliver ◽

Imad Sedki ◽

Rajiv Hanspal

Keyword(s):

Electromagnetic Field ◽

Electromagnetic Fields ◽

Crossover Trial ◽

Phantom Limb Pain ◽

Well Being ◽

Electromagnetic Shielding ◽

Phantom Limb ◽

Phantom Pain ◽

Limb Pain ◽

Double Blind

Background: Environmental electromagnetic fields influence biological systems. Evidence suggests these have a role in the experience of phantom limb pain in patients with amputations. Objectives: This article followed a previous study to investigate the effect of electromagnetic field shielding with a specially designed prosthetic liner. Study design: Randomised placebo-controlled double-blind crossover trial. Methods: Twenty suitable participants with transtibial amputations, phantom pain at least 1 year with no other treatable cause or pathology were requested to record daily pain, well-being, activity and hours of prosthetic use on pre-printed diary sheets. These were issued for three 2-week periods (baseline, electromagnetic shielding (verum) and visually identical placebo liners – randomly allocated). Results: Thirty-three per cent of the recruited participants were unable to complete the trial. The resulting N was therefore smaller than was necessary for adequate power. The remaining data showed that maximum pain and well-being were improved from baseline under verum but not placebo. More participants improved on all variables with verum than placebo. Conclusion: Electromagnetic field shielding produced beneficial effects in those participants who could tolerate the liner. It is suggested that this might be due to protection of vulnerable nerve endings from nociceptive effects of environmental electromagnetic fields. Clinical relevance Electromagnetic field shielding with a suitable limb/prosthesis interface can be considered a useful technique to improve pain and well-being in patients with phantom limb pain.

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Haunting of the phantom limb pain abolished by buprenorphine/naloxone

BMJ Case Reports ◽

10.1136/bcr-2020-237009 ◽

2021 ◽

Vol 14 (2) ◽

pp. e237009

Author(s):

Una Srejic ◽

Faried Banimahd

Keyword(s):

Receptor Antagonist ◽

Opioid Receptor ◽

Drug Effects ◽

Phantom Limb Pain ◽

Pain Syndrome ◽

Local Anaesthetics ◽

Phantom Limb ◽

Limb Pain ◽

Long Acting ◽

Strong Opioids

Neuropathic opioid refractory phantom limb pain (PLP) following amputation can be a life long debilitating chronic pain syndrome capable of completely destroying a patient’s life. The pain, its associated depression and sleep deprivation can make many patients suicidal. Ever changing and relentless, it is notoriously unresponsive to traditional cocktails of strong opioids, adjuvant pain medications, antidepressants, local anaesthetics, nerve stimulators, hypnotics and psychotropics. Drug effects are seldom more effective than placebo. We describe a successful sustained rescue of a difficult 2-year-long PLP case with sublingual buprenorphine/naloxone using the drug’s potent multimodal mechanisms of action: potent long-acting mu agonist/antagonist, kapa receptor antagonist, delta receptor antagonist and novel opioid receptor-like 1 (OR-L1) agonist effects. Traditional escalating pure mu-opioid receptor agonists and adjuvant neuropathic pain cocktails often have disappointing efficacy in the treatment of resistant PLP. We suggest introducing buprenorphine/naloxone as an early effective opioid choice in PLP management.

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