Non-Cochrane · intervention · PM42384353
Botulinum Toxin Type A for Trigeminal and Postherpetic Neuralgia: An Umbrella Review of Systematic Reviews.
De la Torre Canales Giancarlo, Dureisseix Marie-Amélie, Dos Santos Thiago Germano, et al. · Drugs · 2026 · PubMed · doi:10.1007/s40265-026-02352-8
Findings
40 findings
| Population | ||||
|---|---|---|---|---|
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | No comparator (pooled incidence) | Injection-site oedema | Pooled incidence (%) 3.70 GRADE not reported 4 studies · 178 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) | Response rate Mixed follow-up | OR 14.0 [3.9, 56.0] GRADE not reported 13 studies · 672 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | No comparator (pooled incidence) | Injection-site haematoma | Pooled incidence (%) 2.78 GRADE not reported 4 studies · 178 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) | Adequate pain relief | OR 10.24 [4.60, 25.14] Low 11 studies |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) | Response rate Short-term follow-up | OR 3.57 [1.85, 7.14] GRADE not reported 2 studies · 126 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) | Responder rate (>50% pain reduction) End of follow-up (2-3 months) | RR 2.87 [1.76, 4.69] GRADE not reported 2 studies · 122 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) or baseline | Pain intensity (VAS) Up to 6 months | MD -5.88 [-8.37, -3.39] GRADE not reported 4 studies |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) or baseline | Pain intensity (VAS) Overall (all follow-up) | MD -5.19 [-6.05, -4.33] GRADE not reported 13 studies · 484 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) | Pain attack frequency End of follow-up (about 2-3 months) | MD -29.79 [-38.50, -21.08] GRADE not reported 2 studies · 62 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) or baseline | Pain intensity (VAS) 1 month | MD -2.36 [-3.86, -0.87] GRADE not reported 4 studies · 178 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) | Pain intensity (VAS) 1 month | MD -2.89 [-4.66, -1.12] GRADE not reported 3 studies · 114 participants |
| Adults with chronic peripheral neuropathic pain including trigeminal neuralgia (mixed-population review; reported under TN) | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) | Pain intensity (VAS/NRS) 3 months Unresolved: the two extractors disagree on this row. | MD -1.38 [-1.95, -0.81] Moderate 6 studies · 505 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) or baseline | Pain attack frequency 3-6 months | MD -17.85 [-23.36, -12.34] GRADE not reported 8 studies · 279 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) | Pain intensity (VAS) 3 months | MD -3.43 [-5.21, -1.64] GRADE not reported 3 studies · 98 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) | Pain intensity (VAS) 2 months | MD -2.47 [-3.96, -0.99] GRADE not reported 4 studies · 150 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | No comparator (pooled proportion) | Responder rate (>=50% pain reduction), end of treatment period End of treatment period (about 3-6 months) | Pooled proportion 0.707 [0.653, 0.761] GRADE not reported 10 studies · 672 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) or baseline | Pain intensity (VAS) 2 months | MD -2.54 [-4.13, -0.95] GRADE not reported 4 studies · 178 participants |
| Adults with trigeminal neuralgia | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) or baseline | Pain intensity (VAS) 3 months | MD -4.05 [-6.13, -1.97] GRADE not reported 4 studies · 178 participants |
| Adults with postherpetic neuralgia | Botulinum toxin type A (BoNT-A) injection | Other pharmacological treatments | Pain intensity (VAS/NRS) 1 week | MD -3.81 [-5.28, -2.35] GRADE not reported 12 studies · 702 participants |
| Adults with postherpetic neuralgia | Botulinum toxin type A (BoNT-A) injection | Other pharmacological treatments | Pain intensity (VAS/NRS) 1 month | MD -6.92 [-9.96, -3.79] GRADE not reported 12 studies · 702 participants |
| Adults with chronic peripheral neuropathic pain (TN, PHN, post-traumatic) | Botulinum toxin type A injection | Placebo (saline) | Number needed to treat for pain intensity reduction 3 months · Source review: Hary 2022 Unresolved: the two extractors disagree on this row. | NNT 7 Moderate 6 studies · 219 participants |
| Adults with chronic peripheral neuropathic pain (TN, PHN, post-traumatic) | Botulinum toxin type A injection | Placebo (saline) | Sleep score 3 months · Source review: Hary 2022 | SMD -0.04 [-0.43, 0.34] Moderate 2 studies · 104 participants |
| Adults with refractory peripheral neuropathic pain including postherpetic neuralgia | Botulinum toxin type A injection | Placebo (saline) | Pain relief responders (NNT) 3 weeks or longer follow-up · Source review: Soliman 2025 | NNT 2.7 [1.8, 5.1] Moderate 6 studies |
| Adults with chronic peripheral neuropathic pain (TN, PHN, post-traumatic) | Botulinum toxin type A injection | Placebo (saline) | Pain intensity (VAS/NRS) 1 month · Source review: Hary 2022 | MD -1.87 [-2.91, -0.83] Moderate 9 studies · 505 participants |
| Adults with chronic peripheral neuropathic pain (TN, PHN, post-traumatic) | Botulinum toxin type A injection | Placebo (saline) | Sleep score 1 month · Source review: Hary 2022 | SMD -0.75 [-2.02, 0.52] Moderate 3 studies · 134 participants |
| Adults with neuropathic pain including trigeminal neuralgia and postherpetic neuralgia | Botulinum toxin type A injection | Placebo (saline) | Responder rate (50% or greater pain reduction) Not specified · Source review: Finnerup 2015 | Clinically meaningful pain relief favouring BoNT-A; pooled NNT 1.9 to 2.5 for 50% or greater pain reduction (range across definitions; no single estimate) GRADE not reported 6 studies · 137 participants |
| Adults with postherpetic neuralgia | Botulinum toxin type A (BoNT-A) injection | Nerve block | Pain intensity (VAS/NRS) 1 week | MD -2.55 [-4.21, -0.98] GRADE not reported 12 studies · 702 participants |
| Adults with chronic peripheral neuropathic pain (TN, PHN, post-traumatic) | Botulinum toxin type A injection | Placebo (saline) | Pain during injection Not specified · Source review: Hary 2022 | RR 0.99 [0.89, 1.1] High 3 studies · 111 participants |
| Adults with chronic peripheral neuropathic pain (TN, PHN, post-traumatic) | Botulinum toxin type A injection | Placebo (saline) | Number needed to treat for pain intensity reduction 1 month · Source review: Hary 2022 | NNT 3 Moderate 9 studies · 505 participants |
| Adults with postherpetic neuralgia | Botulinum toxin type A (BoNT-A) injection | Nerve block | Pain intensity (VAS/NRS) 1 month | MD -6.81 [-10.18, -3.35] GRADE not reported 12 studies · 702 participants |
| Adults with neuropathic pain including trigeminal neuralgia and postherpetic neuralgia | Botulinum toxin type A injection | Placebo (saline) | Pain reduction Up to 3 months (Table 4); mixed follow-up (Table 8) · Source review: Siongco 2020 | SMD -0.5463 GRADE not reported Studies not reported |
| Adults with neuropathic pain including trigeminal neuralgia and postherpetic neuralgia | Botulinum toxin type A injection | Placebo (saline) | Treatment discontinuation due to adverse events (tolerability) Not specified · Source review: Finnerup 2015 | NNH 83 GRADE not reported 6 studies · 137 participants |
| Adults with postherpetic neuralgia | Botulinum toxin type A (BoNT-A) injection | Pulsed radiofrequency (PRF) | Pain intensity (VAS/NRS) 1 week | MD -1.61 [-3.22, -0.05] GRADE not reported 12 studies · 702 participants |
| Adults with postherpetic neuralgia | Botulinum toxin type A (BoNT-A) injection | Pulsed radiofrequency (PRF) | Pain intensity (VAS/NRS) 1 month | MD -5.10 [-8.35, -1.82] GRADE not reported 12 studies · 702 participants |
| Adults with postherpetic neuralgia | Botulinum toxin type A (BoNT-A) injection | Stellate ganglion block | Pain intensity (VAS/NRS) 1 month | MD -6.43 [-10.06, -2.73] GRADE not reported 12 studies · 702 participants |
| Adults with postherpetic neuralgia | Botulinum toxin type A (BoNT-A) injection | Stellate ganglion block | Pain intensity (VAS/NRS) 1 week | MD -3.78 [-5.67, -1.86] GRADE not reported 12 studies · 702 participants |
| Adults with refractory peripheral neuropathic pain including postherpetic neuralgia (mixed-population review; reported under PHN) | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) | Pain relief responders At least 3 weeks follow-up | SMD 0.5 [0.2, 0.9] Moderate 6 studies |
| Adults with chronic peripheral neuropathic pain including postherpetic neuralgia (mixed-population review; reported under PHN) | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) | Digestive adverse events | RR 0.41 [0.04, 3.97] GRADE not reported 2 studies · 133 participants |
| Adults with refractory peripheral neuropathic pain including postherpetic neuralgia (mixed-population review; reported under PHN) | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) | Withdrawals due to adverse events At least 3 weeks follow-up | NNH 216.3 Moderate 8 studies · 317 participants |
| Adults with chronic peripheral neuropathic pain including postherpetic neuralgia (mixed-population review; reported under PHN) | Botulinum toxin type A (BoNT-A) injection | Placebo (saline) | Neurological adverse events | RR 1.72 [0.73, 4.09] GRADE not reported 2 studies · 133 participants |
Included primary studies 16
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Shehata 2013 Botulinum toxin-type A: could it be an effective treatment option in intractable trigeminal neuralgia? PMID:24251833 | 2013 | 2 other reviews | not stated | not extracted yet |
| Wu 2012 Botulinum toxin type A for the treatment of trigeminal neuralgia: results from a randomized, double-blind, placebo-controlled trial. PMID:22492424 | 2012 | 2 other reviews | not stated | not extracted yet |
| Zhang 2014 Two doses of botulinum toxin type A for the treatment of trigeminal neuralgia: observation of therapeutic effect from a randomized,… PMID:25263254 | 2014 | 2 other reviews | not stated | not extracted yet |
| Zuniga 2013 Acute treatment of trigeminal neuralgia with onabotulinum toxin A. PMID:24045604 | 2013 | 1 other review | not stated | not extracted yet |
| Apalla 2013 Botulinum toxin A in postherpetic neuralgia: a parallel, randomized, double-blind, single-dose, placebo-controlled trial. PMID:23370074 | 2013 | this review only | not stated | not extracted yet |
| Bendtsen 2019 European Academy of Neurology guideline on trigeminal neuralgia. PMID:30860637 | 2019 | this review only | not stated | not extracted yet |
| Finnerup 2015 Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. PMID:25575710 | 2015 | this review only | not stated | not extracted yet |
| Hary 2022 Efficacy and safety of botulinum A toxin for the treatment of chronic peripheral neuropathic pain: A systematic review of randomized… PMID:35293078 | 2022 | this review only | not stated | not extracted yet |
| Hu 2024 Efficacy and Safety of Botulinum Toxin Type A in the Treatment of Trigeminal Neuralgia: An Update on Systematic Review With Meta-analyses. PMID:38385501 | 2024 | this review only | not stated | not extracted yet |
| Morra 2016 Therapeutic efficacy and safety of Botulinum Toxin A Therapy in Trigeminal Neuralgia: a systematic review and meta-analysis of randomized… PMID:27377706 | 2016 | this review only | not stated | not extracted yet |
| Siongco 2020 Botulinum neurotoxin injections for muscle-based (dystonia and spasticity) and non-muscle-based (neuropathic pain) pain disorders: a… PMID:32146504 | 2020 | this review only | not stated | not extracted yet |
| Soliman 2025 Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysis. PMID:40252663 | 2025 | this review only | not stated | not extracted yet |
| Sridharan 2017 Interventions for Refractory Trigeminal Neuralgia: A Bayesian Mixed Treatment Comparison Network Meta-Analysis of Randomized Controlled… PMID:28717987 | 2017 | this review only | not stated | not extracted yet |
| Wen 2020 Efficacy of different interventions for the treatment of postherpetic neuralgia: a Bayesian network meta-analysis. PMID:33317382 | 2020 | this review only | not stated | not extracted yet |
| Xiao 2010 Subcutaneous injection of botulinum toxin a is beneficial in postherpetic neuralgia. PMID:21134121 | 2010 | this review only | not stated | not extracted yet |
| Yang 2018 Efficacy of 8 Different Drug Treatments for Patients With Trigeminal Neuralgia: A Network Meta-analysis. PMID:29200017 | 2018 | this review only | not stated | not extracted yet |
Overlap with other reviews
Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Adults with neuropathic pain, specifically trigeminal neuralgia and postherpetic neuralgia | Adults with trigeminal neuralgia (up to 739 participants) and postherpetic neuralgia (up to 125 participants); mixed neuropathic pain populations in some reviews |
| Intervention | Botulinum toxin (any formulation) | Botulinum toxin type A, 15 to 300 U per session, single or repeated sessions |
| Comparison | Standard treatment, placebo, or other pharmacological and non-pharmacological (surgical) therapies | Placebo (saline), baseline, other pharmacological treatments, nerve block, pulsed radiofrequency, stellate ganglion block |
| Outcomes | Primary: reduction in neuropathic pain intensity (VAS, NRS); secondary: pain frequency, other patient-reported outcomes, adverse events | Pain intensity, attack frequency, responder rate (50% or greater pain reduction), sleep score, adverse events |
| Study designs | Systematic reviews with or without meta-analysis; AMSTAR-2 moderate or high quality only | 10 systematic reviews (7 with meta-analysis; 3 network meta-analyses), 2015 to 2024 (5 high and 5 moderate AMSTAR-2 confidence); 6 overlapping primary RCTs mapped |
| Timing | Short, medium and long term according to reported follow-up | Mostly 1 to 3 months; some up to 6 months |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | Yes | Yes | yes |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Yes | Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes · NRSI: Yes | NRSI: Yes · RCT: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: N/A · NRSI: N/A | NRSI: N/A · RCT: N/A | no |
| 12Impact of risk of bias on the pooled results | N/A | N/A | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | N/A | N/A | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Low | Low | yes |