Table 3.

Pain outcomes: summary of measures and results

First author (year)	Purpose and intervention	Outcome measures	Main findings
Nathan et al. (2017)[63]	Purpose: Evaluate the effectiveness of community-based mindfulness-based stress reduction (MBSR) courses to improve physical and mental functioning among patients with PDPN whose medical treatment has been optimized. Intervention: Nine sessions of MBSR: eight weekly, 2.5-h sessions and one 6-h session on a weekend day midway through the course. Control: Usual activities, offered the opportunity to enroll in a MBSR course once the study was complete	Brief Pain Inventory (BPI) score	BPI Pain Severity mean score decreased in the MBSR group (M = − 1.59, 95% CIs [− 2.29 to − 0.90]) between baseline and week 12, compared to the control group (M = 0.33, 95% CIs [− 0.12 to 0.78], p < 0.001), indicating a reduction in pain in the intervention group.
Yoo et al. (2015)[61]	Purpose: Explore the effect of a supervised, moderate-intensity aerobic exercise training intervention on pain and pain interference in daily life, specifically in people with DPN. Intervention: 16 weeks of supervised aerobic exercise 3 times a week, of 30 to 50 min duration. Control: None	Various measures of pain and pain interference using the Brief Pain Inventory Short Form for Diabetic Peripheral Neuropathy (BPI-DPN) and a questionnaire devised by the authors.	Significant reductions in pain interference observed with walking on mean BPI-DPN score (M = 4.93, SD = 3.03 pre to M = 3.29, SD = 2.89 post, p = 0.016), normal work (M = 5.39, SD = 3.32 pre to M = 3.79, SD = 3.04 post, p = 0.032), relationships with others (M = 3.96, SD = 3.53 pre to M = 1.29, SD = 1.27 post, p = 0.006), sleep (M = 5.11, SD = 3.04 pre to M = 3.50, SD = 3.03 post, p = 0.02), and overall pain interference (M = 4.65, SD = 2.70 pre to M = 2.97, SD = 2.22 post, p = 0.013).
Kluding et al. (2012)[64]	Purpose: Examine the feasibility of a supervised, moderately intense aerobic and resistance exercise program in people with diagnosed diabetic PN. Intervention: 10-week exercise program with both aerobic and strengthening elements, 3 to 4 times per week. Control: None	Michigan Neuropathy Screening Instrument (MNSI) symptom questionnaire	Worst pain MNSI mean score decreased (M = 62.4, SD = 26.7 pre-intervention to M = 44.3, SD = 35.1 post-intervention, p = 0.05).
Forst et al. (2004)[70]	Purpose: Investigate the efficacy and safety of the Salutaris (TENS) device in patients suffering from symptomatic diabetic neuropathy. Intervention: TENS therapy over 12 weeks, self-administered for at least 30 min per day. Control: Electrically inactive (sham) device	Various pain qualities were measured by the Neuropathy Total Symptom Score-6 (NTSS-6), i.e., lancinating, burning, and aching pain, numbness, prickling sensation, and allodynia; pain intensity measured using a Visual Analogue Scale (VAS).	Active TENS treatment resulted in a significant improvement in mean NTSS-6 score after 6 weeks (− 42%) and after 12 weeks (− 32%) of treatment (baseline M = 10.0, SD = 3.3, 6 weeks M = 5.8, SD = 5.0 (p < 0.05), 12 weeks M = 6.8, SD = 3.9, p = 0.05), in comparison to the control group (baseline M = 7.6, SD = 3.1; 6 weeks M = 8.1, SD = 5.1, (n.s.), 12 weeks M = 6.5, SD = 6.1 [n.s.]). Improvement in mean sub-NTSS scores within the intervention group, including numbness (M = 2.19, SD = 1.05 to M = 1.55, SD = 1.26; p < 0.05); lancinating pain (M = 1.58, SD = 1.09 to M = 0.58, SD = 0.86; p < 0.05) and allodynia (M = 1.44, SD = 1.59 to M = 0.53, SD = 1.03; p < 0.05). The intervention group also reported a significant improvement in intervention group mean VAS score after 6 weeks of TENS therapy (M = 19.8, SD = 5.0 to M = 14.4, SD = 9.6; p < 0.05), while no change was observed in the control group.
Kumar and Marshall (1997)[69]	Purpose: Evaluate the efficacy of transcutaneous electrotherapy for chronic painful peripheral neuropathy in patients with type 2 diabetes. Intervention: TENS therapy over 4 weeks, self-administered for 30 min per day. Control: Electrically inactive (sham) device	Grading of pain intensity on a 0–5-point scale; perception of pain using a VAS	Significant reduction in pain grading for those in the intervention group, with the intervention group mean score declining from M = 3.17, SD = 0.12 to M = 1.44, SD = 0.25 (p < 0.01). Significant reduction also reported in the control group, with group mean score declining from M = 2.92, SD = 0.13 to M = 2.38, SD = 0.26 (p = 0.04). Intervention group reported greater reductions in pain through the VAS (M = 52, SD = 7) compared with the control group (M = 27, SD = 10, p < 0.05).
Serry et al. (2015)[71]	Purpose: To investigate the efficacy of TENS versus aerobic exercise and to compare them with regular pharmacological therapy in patients with diabetic PN. Group A: Received TENS therapy for 30 min 3 times per week for 8 weeks in addition to regular pharmacological therapy for PN. Group B: Engaged in aerobic exercise for 30 min 3 times for week for 8 weeks in addition to regular pharmacological therapy for PN. Group C: Received only regular pharmacological therapy for PN and oral hypoglycemic drugs or insulin.	Pain intensity evaluated using a VAS.	Compared to pharmacologic management, both the TENS and exercise groups had significant reductions in mean VAS pain score (TENS group 41.6% reduction, exercise group 16.7% reduction, p < 0.05). Group C (pharmacological management) showed no significant reductions in pain intensity.
Reichstein et al. (2005)[74]	Purpose: To compare the effects of high-frequency muscle stimulation (HF) with TENS therapy in patients with diabetic PN. HF group received HF for 30 min for 3 consecutive days. TENS group received TENS therapy for 30 min for 3 consecutive days.	1–10 point Numerical Rating Scale (NRS) for pain, numbness, burning, parasthesias; or dysesthesia taken at baseline, after all treatment days and 2 days post-intervention.	Reductions in NRS pre and post both interventions; 7 out of 21 patients (33%) in the TENS group and 16 out of 20 patients (80%) in the HF group reported improvement in pain symptoms (p < 0.05). HF more effective than TENS therapy in patients with nonpainful DPN (HF—100%, 7 out of 7; TENS—44%, 4 out of 9; p < 0.05), and in patients with painful DPN (HF—69%, 9 out of 13; TENS—25%, 3 out of 12; p < 0.05).
Gewandter et al. (2018)[72]	Purpose: To inform a future randomized phase 2 study and determine if TENS has the potential to improve CIPN. Intervention: Wireless TENS therapy for at least 1 h twice per day for a 6-week period. Control: None	Short Form McGill Pain Questionnaire-2 (SF-MPQ-2); daily diary containing NRS from 0 to 10 for pain, numbness, tingling, and cramping	NRS median scores indicated reduced pain symptoms post-TENS: pain reduced from a baseline median of 6 (IQR 1.8–6.6) to Mdn 3.7 (IQR 0.42–5.5, p < 0.001), tingling reduced from a baseline median of 5.7 (IQR 4.1–7.1) to Mdn 4 (IQR 1.8–5.1, p = 0.002) post-intervention, numbness from baseline median of 5.5 (IQR 4.7–6.6) to Mdn 4.4 (IQR 3.0–5.2, p < 0.001) post-intervention, and cramping from baseline median 3.0 (IQR 0.3–5.8) to Mdn 1.4 (IQR 0.0–3.1, p < 0.001) post-intervention.
Tonezzer et al. (2017)[73]	Purpose: To evaluate the effects of TENS on CIPN symptoms. Intervention group: 60 min of TENS daily for 45 days. Control: As with intervention with a sham machine	VAS assessing pain and other neuropathy-related symptoms	No significant findings on VAS
Teixeira (2010)[62]	Purpose: The purpose of this pilot study was to evaluate the effectiveness of mindfulness meditation on QoL among adults living with symptomatic diabetic PN. Intervention: The treatment group received instruction in mindfulness meditation and were instructed to listen to guided CD 5 days per week over a 4-week period. Control: Nutritional advice and asked to maintain a food diary for 4 weeks	Pain level using Neuropathic Pain Scale (NPS)	No statistically significant differences between the groups’ post-intervention scores on the NPS

PDPN = painful diabetic peripheral neuropathy; M = mean; CI = confidence interval; DPN = diabetic peripheral neuropathy; SD = standard deviation; PN = peripheral neuropathy; TENS = transcutaneous electrical nervous stimulation; n.s. = not significant; CIPN = chemotherapy-induced peripheral neuropathy; IQR = interquartile range; Mdn = median