The Effect of Botulinum Neurotoxin-A on Blood Flow in Rats: A Potential Mechanism for Treatment of Raynaud Phenomenon

Stone, Austin V.; Koman, L. Andrew; Callahan, Michael F.; Eckman, Delrae M.; Smith, Beth Paterson; Plate, Johannes F.; Smith, Thomas L.

doi:10.1016/j.jhsa.2012.01.021

Cited by 43 publications

(35 citation statements)

References 38 publications

(45 reference statements)

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“…3, 7 Studies in animal models find a positive effect of Btx-A increasing vascular blood flow by inhibiting sympathetic vasoconstriction. 8 Observational studies involving patients with RP report that Btx-A injected into the perivascular space of the affected digits provides significant symptomatic relief. 9-15 Most of these studies are retrospective case series; 10, 11, 13, 15 the two prospective cohort studies published have low internal validity due to lack of randomization, placebo controls, and/or blinding.…”

Section: Introductionmentioning

confidence: 99%

The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma‐Associated Raynaud's Phenomenon: A Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial

Bello

Cooney

Melamed

et al. 2017

Arthritis & Rheumatology

101

126

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Objective To assess the therapeutic efficacy of local injections with Botulinum Toxin Type-A (Btx-A) in improving blood flow to the hands of patients with Raynaud's Phenomenon (RP) secondary to scleroderma. Methods In this randomized, double-blind, placebo-controlled clinical trial (ClinicalTrials.gov #NCT02165111), patients with scleroderma-associated RP received Btx-A (50 units in 2.5 mL) in one randomly selected hand and sterile saline (2.5 mL) in the opposite hand. Follow-up at 1 and 4 months post-injection included Laser Doppler Imaging (LDI) of hands, patient-reported outcomes, and physical exam. We compared outcomes using paired t-test and population average generalized models with generalized estimating equations. Results Of 40 patients enrolled, 25 had limited and 15 diffuse scleroderma. From baseline to 1-month follow-up, there was a greater reduction in average blood flow in Btx-A hands compared to placebo. The model estimated that this difference was statistically significant (average difference: -30.08 flux units, 95% CI: -56.19 to -3.98, p-value=0.024). This difference was mainly influenced by patients with longstanding RP and diffuse scleroderma. Change in blood flow at 4-month follow-up was not significantly different between groups. Clinical measures improved slightly for Btx-A hands in QuickDASH, McCabe score, pain VAS, and Raynaud's Condition Score. Conclusion Our laboratory-based LDI flow data do not support using Btx-A to treat RP in all scleroderma patients. The secondary clinical outcomes suggest some positive, but questionably clinically meaningful effect. The role of Btx-A in treating RP should be further studied with more homogeneous patient populations and in unique clinical situations like acute digital ischemia.

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Section: Introductionmentioning

confidence: 99%

The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma‐Associated Raynaud's Phenomenon: A Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial

Bello

Cooney

Melamed

et al. 2017

Arthritis & Rheumatology

101

126

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“…In clinical practice, BoNTA is used as a vasodilator in treating Raynaud's phenomenon. In a study by Neumeister et al 15 , BoNTA was injected into patients suffering from this condition, with pain and necrotic lesions at the finger extremities 22,23 . After 60 days, all ulcers healed, and 84% of the patients presented improved vascular flow in their hands.…”

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confidence: 99%

Botulinum toxin type A on cutaneous flap viability in diabetic and tobacco-exposed rats

et al. 2015

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PURPOSE:To investigate the effect of Botulinum toxin A (BoNTA) on skin flap viability in healthy, tobacco-exposed and diabetic rats. METHODS:Ninety male Wistar rats (250-300g) were randomly divided into six groups: control+saline (C1), control+BoNTA (C2), tobacco-exposed+saline (T1), tobacco-exposed+BoNTA (T2) diabetes+saline (D1) and diabetes+BoNTA (D2). A dorsal cutaneous flap (3×10cm) was performed. Survival area and total area of the flaps were measured. Lumen diameter, external arterial diameter and lumen/wall thickness ratio were recorded. RESULTS:Survival area increased in control group with BoNTA injection compared with control animals injected with saline (C2 x C1; 0.9±0.1 vs 0.67±0.15, p= 0.001). A similar result was found in diabetes group injected with BontA (D2 x D1; 0.97±0.2 vs 0.61±0.24, p=0.018). No difference was observed in skin flap viability in tobacco-exposed groups (T2 x T1; 0.74±0.24 vs 0.64±0.21, p=0.871).Lumen diameter (p= 0.004), external arterial diameter (p = 0.0046,) and lumen/wall thickness ratio (p= 0.003) were increased in diabetes+BoNTA-treated animals. This effect was not observed in control or in tobacco-exposed groups. CONCLUSIONS:Botulinum toxin A increased skin flap viability in control and diabetic rats on the seventh post-operative day.Increased lumen diameter, external arterial diameter, and lumen/wall thickness ratio were observed in the diabetes+BoNTA group.BoNTA had no effect in the tobacco-exposed group on the seventh postoperative day.

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“…Blocking the release of norepinephrine and other vasoconstrictive substances causes vasodilation at the neuromuscular junction of smooth muscle. This results in an increased blood supply to the digits 11. This is supported by a recent study that found an increase in the viability of skin flaps after Btx-A injection 12…”

Section: Discussionmentioning

confidence: 75%

The novel use of botulinum toxin A for the treatment of Raynaud’s phenomenon in the toes

Dhaliwal¹,

Denton

Butler

2018

BMJ Case Reports

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Raynaud's phenomenon is a vasospastic disorder of the digital vessels triggered by exposure to cold or stress. It is most commonly observed in the hands, but also frequently affects the toes. We present three cases of patients with severe Raynaud's phenomenon in the toes, secondary to scleroderma. The diagnosis of Raynaud's syndrome and scleroderma was established according to the 2010 American College of Rheumatology and European League Against Rheumatism criteria. Patients were treated with 10 units of botulinum toxin injected into each foot. Two millilitres was injected into the base of each toe in both the left and right feet. Six weeks postinjection into the toes, patients reported an improvement of cold intolerance, colour change and frequency and severity of Raynaud's attacks. The effects were reported to last up to 5 months. To our knowledge, these are the first reported cases of the treatment of Raynaud's phenomenon in the toes with botulinum toxin A.

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The Effect of Botulinum Neurotoxin-A on Blood Flow in Rats: A Potential Mechanism for Treatment of Raynaud Phenomenon

Cited by 43 publications

References 38 publications

The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma‐Associated Raynaud's Phenomenon: A Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial

The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma‐Associated Raynaud's Phenomenon: A Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial

Botulinum toxin type A on cutaneous flap viability in diabetic and tobacco-exposed rats

The novel use of botulinum toxin A for the treatment of Raynaud’s phenomenon in the toes

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