Is Botulinum Toxin Effective in Treating Orofacial Neuropathic Pain Disorders? A Systematic Review
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy and Criteria for Selecting Articles and Registration
2.2. Inclusion Criteria
2.3. Exclusion Criteria
2.4. Selection of Participants
2.5. Methods
2.6. Statistical Analysis
2.7. Quality of RCT Selected
2.8. Outcome
- Pain levels were evaluated using a reliable, validated scale, like the visual analogue scale (VAS);
- If a validated tool was available, health-related quality of life was assessed;
- The percentage of participants who experienced major adverse events were measured, including life-threatening situations, hospitalization, or incidents that caused serious disability or incapacity (e.g., infection, dysphagia);
- Participants with at least 1 adverse event (e.g., hypersensitivity reactions such as anaphylaxis, urticaria, soft tissue oedema, dyspnea, or allergic reaction) were evaluated.
- Function was assessed by a validated questionnaire;
- Utilisation of analgesic medication was assessed by type and dose used per day.
3. Results
3.1. Study Characteristics
3.2. Quality of RCTs Selected
3.3. Types, Number of Administrations, Sites and Doses of Botulinum Toxin, and Side-Effects
3.4. Period of Follow-Up and Quality of Life and Pain Assessments
3.5. Effect on Pain Reduction
3.6. Quality of Life
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
References
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Study | Year | Diagnosis | Sample Size (Test/Control) | Test/Control | Site of Injection | Repeated Injection | Weeks between First and Second Injection | Follow-Up | Drop-Out |
---|---|---|---|---|---|---|---|---|---|
Shehata [36] | 2013 | Trigeminal Neuralgia | 20 (BTX 10: saline10) | BTX-A (Botox®) (100 U Botox in 2 mL preservative-free normal saline, resulting in a concentration of 5 units/0.1 mL) or placebo (2 mL 0.9% NaCl). | “follow the pain” method. If the branch of the mandible is affected, a higher amount of toxin is injected at the back of the masseter muscle to prevent any unwanted cosmetic outcomes. | No | 0 | 12 weeks | 0 |
Wu [37] | 2012 | Trigeminal Neuralgia | 42 (BTX 22: saline 20) | intradermal and/or submucosal injection of BTX-A (75 U/1.5 mL;) or saline (1.5 mL) | “follow the pain” method. | No | 0 | 12 weeks | 2 |
Xiao [12] | 2010 | Postherpetic neuralgia | 60 (20:20:20) | The lidocaine group (0.5% lidocaine) acted as an active control. Non-preserved saline (0.9%) was used for the placebo group. For the BTX-A group, aliquots of 100 IU/vial of BTX-A were reconstituted with 20 mL of saline solution. | Subjects received subcutaneous injections into the affected area, specifically the area demonstrating evidence of tactile allodynia. | No | 0 | 3 months | 4 |
Zhang [34] | 2017 | Trigeminal Neuralgia | 100 (50:50) | Patients in the single-dose group received a local BTX-A injection of 70 to 100 U. The repeated-dose group received an initial BTX-A injection of 50 to 70 U and then another of equal volume 2 weeks later. | “follow the pain” method | Yes | 2 weeks | 6 months | 19 |
Zhang [33] | 2014 | Trigeminal Neuralgia | 84 placebo (n = 28); BTX-A 25 U (n = 27); BTX-A 75 U (n = 29) | Each vial contained either active botulinum toxin type A (25 U or 75 U) or matching placebo. All three vials were identical in appearance and were reconstituted with 1 mL saline solution (0.9%). For treatment, 1 mL was drawn from vials, and the injections were administered intradermally and/or submucosally. | “follow the pain” method | No | 0 | 8 weeks | 0 |
Zúñiga [35] | 2013 | Trigeminal Neuralgia | 36 (BTX 20: saline 16) | 1 mL 0.9% saline plus 50 U of BTX or only 1 mL of 0.9% saline injected subcutaneously in the affected area. | Among the path of the branch/branches involved, patients with involvement of the third branch of the trigeminal nerve also received intramuscularly either 10 U of BTX or matching placebo in the masseter muscle, ipsilateral to the pain location. | No | 0 | 3 months | 5 |
Study | Year | Type of Study | Level of Evidence | Jadad Score |
---|---|---|---|---|
Shehata [36] | 2013 | RCT double blind | II | 5 |
Wu [37] | 2012 | RCT double blind | II | 4 |
Xiao [12] | 2010 | RCT double blind | II | 4 |
Zhang [34] | 2017 | RCT | I | 2 |
Zhang [33] | 2014 | RCT double blind | II | 2 |
Zúñiga [35] | 2013 | RCT double blind | II | 3 |
Study | Year | Results in Pain Management |
---|---|---|
Shehata [36] | 2013 | Pain reduction at the 12-week endpoint was significant in the BTX group (p < 0.0001). The BTX-A group showed a decrease in VAS scores starting from week 2 and maintained it throughout the follow-up period. Furthermore, a significant reduction in paroxysm frequency was observed in the BTX-A group compared to the placebo group from week 2 onwards (p < 0.0001). |
Wu [37] | 2012 | At week 2, BTX-A showed a significant decrease in the average VAS scores compared to the placebo. The results showed that BTX-A was significantly better than the placebo in reducing the frequency of attacks. This effect was noticeable as early as the first week. |
Xiao [12] | 2010 | The VAS pain scores decreased in all three groups at day 7 and 3 months after treatment (p < 0.01). The group that received BTX-A had a greater decrease in VAS pain scores compared to the lidocaine and placebo groups, which was more significant at day 7 and 3 months after treatment (p < 0.01). Out of the three groups tested, the BTX-A group had the lowest percentage (21.1%) of subjects using opioids after treatment, compared to the lidocaine (52.6%) and placebo (66.7%) groups. This difference was statistically significant (p < 0.01). |
Zhang [34] | 2017 | The group that received a single dose of the drug had a noticeably longer effect time (p = 0.032). The drug response rates between the single-dose and repeated-dose groups did not show significant differences (p > 0.05). |
Zhang [33] | 2014 | During the study, the groups that received doses of 25 U and 75 U experienced a significant reduction in VAS scores compared to the placebo group as early as week 1. Throughout the study, there was no significant difference in VAS scores between the 25 U and 75 U groups. At week 8, the response rates for the 25 U group (70.4%) and 75 U group (86.2%) were significantly higher than the response rate for the placebo group (32.1%). However, there was no significant difference in response rates between the 25 U and 75 U groups. |
Zúñiga [35] | 2013 | After three months of the injection, a noticeable contrast was detected in the average VAS score between individuals who received BTX treatment and those who received placebo treatment (VAS 4.75 vs. 6.94, respectively; t-test, p = 0.01). |
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Val, M.; Delcanho, R.; Ferrari, M.; Guarda Nardini, L.; Manfredini, D. Is Botulinum Toxin Effective in Treating Orofacial Neuropathic Pain Disorders? A Systematic Review. Toxins 2023, 15, 541. https://doi.org/10.3390/toxins15090541
Val M, Delcanho R, Ferrari M, Guarda Nardini L, Manfredini D. Is Botulinum Toxin Effective in Treating Orofacial Neuropathic Pain Disorders? A Systematic Review. Toxins. 2023; 15(9):541. https://doi.org/10.3390/toxins15090541
Chicago/Turabian StyleVal, Matteo, Robert Delcanho, Marco Ferrari, Luca Guarda Nardini, and Daniele Manfredini. 2023. "Is Botulinum Toxin Effective in Treating Orofacial Neuropathic Pain Disorders? A Systematic Review" Toxins 15, no. 9: 541. https://doi.org/10.3390/toxins15090541
APA StyleVal, M., Delcanho, R., Ferrari, M., Guarda Nardini, L., & Manfredini, D. (2023). Is Botulinum Toxin Effective in Treating Orofacial Neuropathic Pain Disorders? A Systematic Review. Toxins, 15(9), 541. https://doi.org/10.3390/toxins15090541