Table 1.

Study characteristics of individual studies

Author Year (Country)	Design	Population, Age, Sex, Cause of Amputation	No. of Patients	Intervention	Stimulation Location and Procedure	Control	Outcome (VAS or NRS) and P Value
Ahmed 2011 (Egypt)	RCT	Outpatients Age: I: 52 ± 12.7 y, C: 53 ± 13.3 y Sex: I: M = 13 (76.5%), F = 4 (23.5%), C: M = 6 (60%), F = 4 (40%) Cause: I: traumatic = 2 (11.8%), ischemic = 6 (35.3%), diabetic = 17 (100%), C: traumatic = 4 (40%), ischemic = 2 (20%), diabetic = 10 (100%)	I: 17, C: 10	rTMS: High frequency: 20 Hz, 10-sec trains (200 pulses) every minute, intensity of stimulation: 80% of resting motor threshold, 10-min sessions daily for 5 consecutive d	Optimal scalp position determined from where transcranial magnetic stimulation evoked motor potentials of maximum peak-to-peak amplitude in the muscle proximal to the stump	Sham stimulation: coil elevated and angled away from the head	I = 3.4 ± 1.2, C = 7.4 ± 0.84 (P = 0.001)
Malavera 2016 (Colombia)	RCT	Outpatients Age: I: 33.1 ± 6.6 y, C: 34.7 ± 9.9 y Sex: I: M = 25, F = 2, C: M = 25, F = 2 Cause: traumatic	I: 27, C: 27	rTMS: Frequency: 10 Hz, 20-min sessions, 20 trains of 6 sec (54-sec intertrain interval), intensity of stimulation: 90% of motor threshold, daily sessions for 10 d during a 2-wk period	M1 contralateral to the amputated leg (corresponding to the first dorsal interosseous muscle of the hand contralateral to pain)	Sham stimulation (sham coil)	I = 2.28 ± 2.51, C = 3.71 ± 2.97 (P = 0.03)
Irlbacher 2006 (Germany)	RCT – crossover	Outpatients Age: 46.6 ± 12.6 y Sex: M = 8, F = 6 Cause: not mentioned	14	rTMS: Frequency: rTMS 1 Hz, 5 Hz, 500 pulses per session, intensity of stimulation: 95%, daily sessions for 5 consecutive d	M1 area corresponding to affected phantom limb. Optimal placement defined by maximal motor response	Sham stimulation: 2 Hz, identical placement of coil that looks and sounds identical and produces same scalp sensation	I (1Hz) = 4.22 ± 2.79, I (5Hz) = 4.99 ± 2.33, C (2Hz) = 4.37 ± 2.97 (P = 0.02)
Bolognini 2013 (Italy)	RCT – double-blind, sham-controlled crossover	Outpatients Age: 35–81 y Sex: M = 6, F = 2 Cause: ischemic = 5, traumatic = 2, cancer = 1	8	Trial 1: anodal tDCS, frequency NR, 15-min sessions, intensity: 2 mA Trial 2: anodal tDCS, cathodal tDCS, frequency NR, 15-min sessions, intensity: 2 mA	Trial 1: M1 Anodal electrode placed over C3 or C4 to target hemisphere contralateral to amputation, cathode electrode placed over contralateral supraorbital area Trial 2: PPC Hemisphere contralateral to amputation, active electrode placed over P3 or P4, reference electrode placed over contralateral supraorbital area	Trial 1: Sham stimulation (stimulator turned off after 30 sec) Trial 2: Sham stimulation (stimulator turned off after 30 sec)	I = 0.8 (−69%), C = 2.6 (−21%, P = 0.02)
Bolognini 2015 (Italy)	RCT – double-blind, sham-controlled crossover	Outpatients Age: 22–76 y Sex: M = 3, F = 5 Cause: ischemic = 6, traumatic = 2	8	Anodal tDCS, 15-min session, ramping period of 10 sec at beginning and end, intensity of 1.5 mA, 5 consecutive d	M1 Anodal electrode placed over C3 or C4 to stimulate M1 contralateral to the amputation, cathode electrode over the contralateral supraorbital area	Sham stimulation (current lasted for 30 sec)	I = 3.3 (−41%), C = 4.7 (−17%, P = 0.04)
Kikkert 2018 (UK)	RCT – double-blind sham-controlled crossover	Outpatients Age: 47 ± 3 y Sex: M = 11, F = 6 Cause: ischemic = 1, traumatic = 13, cancer = 1	8	tDCS (anodal, amputation contralateral M1, cathodal, amputation ipsilateral supraorbital area) 3 sessions, active 1 session, 20 min, 1mA	M1 Electrode placement followed standard procedures and was determined according to the EEG 10-20 system	Sham:The stimulator was turned off after the impedance was stable (after ∼30 sec)	I = 1.73 ± 3.05 (−29.5%), C = 2.50 ± 2.56 (1.2%, P = 0.01)
Katz 1991 (Canada)	RCT – controlled crossover	Outpatients Age: 52.8 (23–73) y Sex: M = 18, F = 10 Cause: peripheral vascular disease (including diabetes mellitus) = 12, accident = 9, arterial thrombosis in 3, tumor = 2, radiation damage = 1, polio = 1	11/28	TENS, 30 min (each session was divided into three consecutive 10-min periods, including an initial resting baseline [B1], bilateral ear stimulation [BES], and a final resting baseline [B2]). Throughout the 30-min session, the subject monitored changes in (painful and/or nonpainful) phantom limb intensity by turning the dial, 1 d	Outer ears (auricular, bilateral ear stimulation)	Placebo	I = 5.1 ± 1.05, C = 9.0 ± 2.16 (P < 0.01)
Tilak 2016 (India)	RCT	Outpatients Age: I = 36.38 ± 9.55 y, C = 42.62 ± 10.69 y Sex: I: M = 11 (84.6%), F = 2 (15.4%), C: M = 12 (92.3%), F = 1 (7.7%) Cause: not mentioned	26	TENS, (contralateral leg) 20 min, one session of TENS for 4 consecutive d	Contralateral leg at the site exactly where they have PLP on the amputated leg	Mirror therapy	I = 2.46 ± 1.561, C = 2.08 ± 1.621 (P = 0.003)
Brede 2017 (USA)	RCT	Outpatients Age: I: 25.7 ± 5.9 y, C: 26.1 ± 5.9 y Sex: I: M = 22 (96%), F = 1 (4%), C: M = 21 (100%), F = 0 (0%) Cause: Blast injuries from improvised explosive devices and landmines were the most common source of trauma	44	MARP + NMES (15 min/session on 5 days/wk) to stimulate contractions for 12 wk	Quadriceps muscles of both legs	MARP only	I = 0.8 ± 0.7, C = 1.6 ± 0.7 (P = 0.005)
Mulvey 2013 (UK)	QE	Outpatients Age: 22–72 (54 ± 13.8) y Sex: M = 4, F = 6 Cause: vascular = 4, trauma = 5, BKN reamputation = 1	10	TENS (60 min) one time	Above stump = 8, on stump = 2	–	−1.8 ± 1.6 (P < 0.05)
Kawamura 1997 (Japan)	QE	Outpatients Age: 22–72 (54 ± 13.8) y Sex: M = 4, F = 6 Cause: vascular = 4, trauma = 5, BKN reamputation = 1	10	Arteriosclerosis obliterans, malignant tumor, or trauma	The sites of the contralateral limb that exactly corresponded to the sites of the amputated limb where the patients felt	–	−1.2 ± 1.9 (P < 0.001)
Rauck 2014 (USA)	QE	Outpatients Age: 47 ± 12 y Sex: M = 14 (88%), F = 2 (12%) Cause trauma = 11 (69%), vascular disease or dysfunction = 4 (25%), cancer = 1 (6%)	9/16	Peripheral nerve stimulation for two weeks	Needle electrode was inserted into the trunk of a major peripheral nerve (i.e., the femoral nerve trunk and/or the sciatic nerve trunk)	–	−81% ± 28% (P < 0.002)
Pereira 2013 (UK)	QE	Outpatients Age: 45–71 y Sex: M = 3, F = 2 Cause: traumatic	5	DBS Initial frequency: 10 Hz in three patients, 20 Hz in two patients, 30 Hz in one patient. Frequency at 3 years: 10 Hz in four patients, 15 Hz in one patient, 20 Hz in one patient	Contralateral, ventroposterolateral nucleus of the sensory thalamus targeted. Effect of macrostimulation assessed from 2 mm above to 5 mm below the calculated target to elicit paresthesia or analgesia Quadripolar electrodes. Final electrode position determined by intraoperative clinical assessment that relied on subjective reporting by awake patient during 48-h period of postoperative clinical assessment before decision on whether to permanently implant electrodes	–	−2.8 ± 2.6 (−65.3% ± 25%, P = 0.001)
Bittar 2005 (Australia)	QE	Outpatients Age: 38–76 y Sex: M = 3 Cause: vascular insufficiency = 1, traumatic = 2	3	DBS Implanted electrodes had four exposed contacts, each 1.5 mm long, arranged linearly with 1.5 mm in between. Location was adjusted to find site of greatest pain relief. Several days of testing before generator implanted	DBS (contralateral) of PVG and somatosensory thalamus. Two patients: PVG only. One patient: PVG and thalamic stimulation	–	−6.17% ± 7.4% (range = 55–70%, P = 0.02)

BKN = below knee; C = control; DBS = deep brain stimulation; EEG = electroencephalography; I = intervention; F = female; M = male; MARP = military amputee rehabilitation program; NMES = neuromuscular electrical stimulation; NR = not reported; NRS = numeric rating scale; PLP = phantom limb pain; PVG = ; QE = quasi-experimental; RCT = randomized controlled trial; rTMS = transcranial magnetic stimulation; tDCS = transcranial direct current stimulation; TENS = transcutaneous electrical nerve stimulation; VAS = visual analog scale.