Table 1.
Summary of studies on botulinum toxin for neuropathic pain.
| References | AAN Class | Study Type (Design) | Number of Patients | Diagnosis | Injection Route/Site/Serotype/Dose | Result |
|---|---|---|---|---|---|---|
| Xiao et al. [18] (2010) | I | Randomized, double-blind, placebo-controlled | 60 | Post-herpetic neuralgia | Subcutaneously/over the area of allodynia/BoNT/A/5 IU per site | VAS reduction and sleep quality improvement; superior to control group |
| Apalla et al. [67] (2013) | I | Randomized, double-blind, placebo-controlled | 30 | Post-herpetic neuralgia | Subcutaneously/over the affected area in a chessboard manner/BoNT/A/5 IU per point (Total 100 IU) | VAS at least 50% reduction in 13 patients in the intervention group and significant reduction in sleep scored |
| Ranoux et al. [16] (2008) | I | Randomized, double-blind, placebo-controlled | 29 (4 post-herpetic) | Post-herpetic neuralgia or post-traumatic/post-surgery neuropathy | Intradermally/into painful area/BoNT/A/20–190 IU | Decreased VAS, burning sensation, allodynic brush sensitivity, a reduced number of pain paroxysms, and improvements in quality of life |
| Liu et al. [68] (2006) | IV | Case report | 1 | Post-herpetic neuralgia | Subcutaneously/over the all painful area in a fan pattern/BoNT/A/100 IU | VAS reduction from 10 to 1 (lasting for 52 days) |
| Sotiriou et al. [69] (2009) | IV | Case series | 3 | Post-herpetic neuralgia | Subcutaneously/20 injection in a chessboard pattern/BoNT/A/100 IU | VAS decreased within three days (lasting for 64 days) |
| Wu et al. [70] (2012) | I | Randomized, double-blind, placebo-controlled, parallel design | 42 (22 BoNT, 20 placebo) | Trigeminal Neuralgia | Intradermally or submucosally/into trigger zones/BoNT/A/75 IU | Reduction in VAS (>50%) in 68% (BoNT group) vs. 15% (placebo group) |
| Bohluli et al. [71] (2011) | IV | Prospective, open, case series | 15 | Trigeminal Neuralgia | Not specified injection mode/into trigger zones/BoNT/A/50–100 IU | 100% improvement in global assessment scale, frequency of pain attacks, and VAS scores |
| Zúñiga et al. [72] (2008) | IV | Prospective, open, case series | 12 | Trigeminal Neuralgia | Subcutaneously/into trigger zones/BoNT/A/20–50 IU | Reduction in VAS (from 8.8 to 4) and number of paroxysmal attacks in 10 patients (lasting for two months) |
| Türk et al. [73] (2005) | IV | Prospective, open, case series | 8 | Trigeminal Neuralgia | Two points (depth 1.5–2 cm) around zygomatic arch/BoNT/A/50 IU per point (total 100 units) | Reduction in VAS and the frequency of attacks (100%) |
| Piovesan et al. [74] (2005) | IV | Prospective, open pilot study | 13 | Trigeminal Neuralgia | Subdermally/painful area in a grid pattern/BoNT/A/3 IU per point (total 6–9 IU) | Reduction in VAS for 60 days (100%: Pain-free (4), more than 50% reduction (9)) |
| Borodic et al. [75] (2002) | IV | Prospective, open pilot study | 11 | Trigeminal Neuralgia | Subdermally or Intradermally/subcutaneous trigger zones (depth 1–3 mm, 10 mm apart)/BoNT/A/total 30–50 IU | Reduction in pain (>50%) in eight patients and frequency (lasting for 2–4 months) |
| Ngeow and Nair [76] (2001) | IV | Case report | 1 | Trigeminal Neuralgia | Subcutaneously/two trigger zones over painful area/BoNT/A/100 IU total | Complete pain relief in nasal area and partial at mental region |
| Yoon et al. [77] (2010) | IV | Case report | 1 | Trigeminal Neuralgia | Subcutaneously/one point in the middle chin/BoNT/A/10 IU | Decreased painful area and pain intensity |
| Allam et al. [78] (2005) | IV | Case report | 1 | Trigeminal Neuralgia | Subcutaneous/eight points along the area of V1 and V2/BoNT/A/2 IU per point (total 16 IU) | Reduction in pain (lasting for 90 days) |
| Layeeque et al. [79] (2004) | IV | Prospective, non-randomized, placebo-controlled | 48 (22 BoNT, 26 control) | Post-surgical neuralgia | Pectoralis major, serratus anterior, and rectus abdominis muscles/BoNT/A/100 IU | Significantly reduced post-surgical pain and facilitated reconstruction with tissue expander |
| Yuan et al. [17] (2009) | II | Randomized, double-blind, placebo-controlled, crossover trial | 20 | Diabetic neuropathy | Intradermally/into the dorsum of the foot in a grid distribution patterns/BoNT/A/4 IU per site (50 units into each foot) | Significant VAS reduction at one, eight, and 12 weeks after injection (lasting for 12 weeks) and improvement in sleep quality in BoNT group |
| Ghasemi et al. [80] (2014) | I | Randomized, double-blind, placebo-controlled | 40 | Diabetic neuropathy | Intradermally/in a grid distribution pattern of 12 sites across the dorsum of the affected foot/BoNT/A/100 IU | Reduced NPS scores and DN4 scores and 30% patients pain-free in intervention groups |
| Kapural et al. [81] (2007) | IV | Retrospective, open, case series | 6 | Occipital Neuralgia | Perineural/occipital nerve block/BoNT/A/50 IU | Reduction of VAS and Pain Disability Index Scores in five of six patients at four weeks |
| Taylor et al. [82] (2008) | IV | Prospective, open, case series | 6 | Occipital Neuralgia | Perineural/around the occipital nerve/BoNT/A/100 IU | Significant improvement in sharp/shooting pain scores |
| Breuer et al. [83] (2006) | I | Randomized, double-blind, placebo-controlled | 20 | Carpal tunnel syndrome | Intramuscularly/into three hypothenar muscles/BoNT/B/2500 IU | No difference compared with the placebo group |
| Tsai et al. [84] (2006) | IV | Prospective, open, pilot study | 5 | Carpal tunnel syndrome | Intracarpally/on each side of the carpal tunnel/BoNT/A/60 IU | Insignificant trend toward pain improvement at three months without change in conduction time by NCS in three patients |
| Safarpour et al. [85] (2010) | III | 1. Randomized, double- blind, placebo-controlled study; 2. uncontrolled, unblended, open-label study | 14 (8 BoNT/A, 6 control) | CRPS | Intradermally and subcutaneously/into the allodynic area/BoNT/A/5 IU per point (total 40–200 units) | No response to the BoNT in VAS; study terminated prematurely because of injection intolerance |
| Carroll et al. [86] (2009) | III | Randomized, double-blind, placebo-controlled crossover trial | 18 (9 crossover study) | CRPS | Lumbar sympathetic block/BoNT/A/Bupivacaine 0.5% + 75 IU of BoNT/A | Longer duration of pain reduction (median 71 days) in BoNT/A group than the control group (median 10 days) |
| Kharkar et al. [87] (2011) | IV | Retrospective, uncontrolled, nblended study | 37 | CRPS | Intramuscularly/neck or upper limb girdle muscles/BoNT/A/10–20 IU per muscle (total 100 IU) | The 97% patients reported reduction of pain by 43% |
| Argoff et al. [54] (1999) | IV | Prospective, open, case series | 11 | CRPS | Subcutaneously/into shoulder girdle muscles/BoNT/A/25–50 IU (total 300 IU) | Reduction in VAS, allodynia, and hyperalgesia and improved skin color |
| Safarpour and Jabbari [88] (2010) | IV | Case series | 2 | CRPS | Intramuscularly/trigger points in the proximal muscles/BoNT/A/20 IU per site | Reduction in proximal and distal pain of myofascial pain syndrome and CPRS |
| Wu et al. [89] (2012) | III | Prospective, randomized, double-blind pilot study | 14 | Residual limb pain or phantom limb pain | Intramuscular and cutaneous/subcutaneously/into focal tender points BoNT/A, 50 IU per site (total 250–300 IU) | Reduced residual limb pain, compared with the lidocaine/depomedrol group; not effective for phantom limb pain |
| Jin et al. [90] (2009) | IV | Case series | 3 | Residual limb pain or phantom limb pain | Electromyography (EMG)-guided injection/into the painful stumps points with strong fasciculation/BoNT/A/500 IU | Significant pain reduction, improved prosthesis tolerance, and reduced pain medication (100%) |
| Kern et al. [91] (2004) | IV | Case report | 1 | Residual limb pain or phantom limb pain | Into trigger points of the stump/BoNT/A/4 × 25 IU | Almost completely pain-free and reduced pain medication |
| Uyesugi et al. [92] (2010) | IV | Case report | 1 | Painful keloid | Subcutaneously/throughout the scar in a fan-like distribution BoNT/A, total 100 IU | Reduction in VAS (from 8 to 6) at five weeks and time periods of pain-free increased |
| Jabbari et al. [93] (2003) | IV | Case Report | 2 | Spinal cord injury | Subcutaneously/into the area of burning pain and allodynia (16 to 20 sites)/BoNT/A, 5 IU per site | Significant improvement in VAS (burning pain and allodynia lasting at least three months) |
| Han et al. [94] (2014) | IV | Case Report | 1 | Spinal cord injury | Subcutaneously/into 10 most painful sites of each sole/BoNT/A/20 IU per site | Reduction in VAS from 96 mm to 68 mm and decreased intensity of the paroxysmal bursts VAS 23 mm after eight weeks |
BoNT/A: botulinum toxin type A; CRPS: complex regional pain syndrome; VAS: visual analog scale.