title: Two doses of botulinum toxin type A for the treatment of trigeminal neuralgia: observation of therapeutic effect from a randomized, double-blind, placebo-controlled trial Botulinum Toxin A in Postherpetic Neuralgia: A Parallel, Randomized, Double-Blind, Single-Dose, Placebo-controlled Trial Botulinum toxin-type A: could it be an effective treatment option in intractable trigeminal neuralgia? Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial Botulinum toxin injection for management of thoracic outlet syndrome: A double-blind, randomized, controlled trial Botulinum toxin type A for the treatment of trigeminal neuralgia: results from a randomized, double-blind, placebo-controlled trial Clinically significant placebo analgesic response in a pilot trial of botulinum B in patients with hand pain and carpal tunnel syndrome. A Prospective Randomized Double-blinded Pilot Study to Examine the Effect of Botulinum Toxin Type A Injection Versus Lidocaine/Depomedrol Injection on Residual and Phantom Limb Pain: Initial Report Electrophysiologically identified piriformis syndrome is successfully treated with incobotulinum toxin a and physical therapy Acute Treatment of Trigeminal Neuralgia With Onabotulinum Toxin A Subcutaneous injection of botulinum toxin a is beneficial in postherpetic neuralgia. Botulinum toxin type-A (BOTOX) in the treatment of occipital neuralgia: a pilot study.
abstract: Background In the majority of cases , trigeminal neuralgia ( TN ) is a unilateral condition with ultra-short stabbing pain located along one or more branches of the trigeminal nerve . Although prophylactic pharmacological treatment is first choise , considering of insufficient effect or unacceptable side effects , neurosurgical treatment or lesion treatment should be considered . In addition to all these procedures mentioned above , one approach has been based on local intradermal and /or submucosal injections of Botulinum Toxin Type A ( BTX-A ) . Methods We conducted a r and omized , double-blind , placebo-controlled since November 2012 , and adopted local multi-point injection in 84 cases of classical TN with different doses of BTX-A. Eighty four patients were r and omized into following groups : placebo ( n = 28 ) ; BTX-A 25U  ( n = 27 ) ; BTX-A 75U ( n = 29 ) . Follow-up visits were conducted every week after the injection , and the overall duration of the study for each patient were 8 weeks to observe the pain severity , efficacy and adverse reactions at endpoint . Results The visual analogue scale ( VAS ) scores of 25U and 75U groups reduced significantly compared to placebo as early as week 1 , and sustained until week 8 throughout the study . There was no significant difference in VAS between 25U and 75U groups throughout the study . The response rates of 25U group ( 70.4 % ) and 75U group ( 86.2 % ) were significantly higher than placebo group ( 32.1 % ) at week 8 , and there was no significant difference between 25U and 75U groups . Evaluation of the Patient Global Impression of Change ( PGIC ) demonstrated that 66.7 % ( 25U group ) and 75.9 % ( 75U group ) of the patients reported that their pain symptoms were ‘ much improved ’ or ‘ very much improved ’ versus 32.1 % of the placebo group , and there was also no significant difference between 25U and 75U groups . All adverse reactions were grade d as mild or moderate . Conclusions BTX-A injection in TN is safe and efficient . It is a useful treatment for refractory TN . Lower dose ( 25U ) and high dose ( 75U ) were similar in efficacy in short-term Objectives : Cumulative evidence support a beneficial effect of botulinum toxin A ( BTX-A ) in postherpetic neuralgia ( PHN ) . We aim ed to assess efficacy , safety , and tolerability of BTX-A in the management of PHN , performing a r and omized , double-blind , single-dose , placebo-controlled trial . Methods : Thirty adults with PHN were r and omized either to BTX-A or placebo .  Severity of pain was evaluated by patients using a visual analogue scale ( VAS ) and quality of sleep was assessed using a 5-item question naire . Primary outcome was reduction in VAS score , with a greater than 50 % reduction being considered clinical ly significant . Secondary outcomes were reduction in sleep score and maintenance of VAS score after treatment , with over 50 % maintenance considered clinical ly meaningful . Results : Thirteen patients from the experimental arm achieved an at least 50 % reduction in VAS score , compared with none of the placebo patients ( NNT=1.2 , 95 % CI , 2 - 1 ; ARR=0.87 , 95 % CI , 055 - 096 ; P<0.001 ) . BTX-A patients showed significant reduction in VAS pain scores between baseline and week 2 , which persisted for a median period of 16 weeks . BTX-A patients showed significant reduction in sleep scores between baseline and week 2 , which remained unchanged until 16th week ( P<0.001 ) . Treatment was well tolerated . Discussion : Data confirm that BTX-A is effective and well tolerated in the treatment of PHN Background Botulinum toxin type A ( BTX-A ) has been reported to have analgesic effects independent of its action on muscle tone , mostly by acting on neurogenic inflammatory mediators and controlling the neurotransmitter release of sensory and autonomic nerve terminals that are involved in many chronic painful conditions as chronic intractable trigeminal neuralgia (TN).The aim of our work was evaluating the efficacy , safety , and tolerability of BTX-A for the treatment of intractable idiopathic TN . Methods This was a r and omized , single-blinded , placebo-control study carried out on 20 Egyptian patients with intractable TN . Patients received a one-time subcutaneous administration of BTX-A using “ follow the pain ” method . The primary efficacy measure was reduction in pain severity on the 10-cm VAS score as well as in paroxysms frequency from the baseline to week 12 ( endpoint last observation carried forward [ LOCF ] ) . Secondary efficacy measures included QoL assessment and number of acute medications received from baseline to the endpoint . Results Pain reduction at the 12-week endpoint was significant in BTX-A group ( p<0.0001 ) ; VAS scores at endpoint LOCF relative to baseline for BTX-A group showed a decrease of 6.5 compared with a decrease of 0.3 for placebo , also there was a significant decrease in the number of acute medications and an increase in QoL functioning scale . Conclusion These results indicate that BTX-A has a direct analgesic effect in patients with TN and can represent a therapeutic option for intractable cases BACKGROUND Data from previous studies suggest that botulinum toxin A has analgesic effects against peripheral neuropathic pain , but the quality of the evidence is low . We aim ed to assess the safety and efficacy of repeated administrations of botulinum toxin A in patients with neuropathic pain . METHODS We did a r and omised , double-blind , placebo-controlled trial at two outpatient clinics in France ( Clinical Pain Centre , Ambroise Paré Hospital , APHP , Boulogne-Billancourt , and Neurological Centre , Hôpital Dupuytren , Limoges ) and one in Brazil ( Neurological Department , Hospital das Clínicas da FMUSP , São Paulo ) . Patients aged 18 - 85 years with peripheral neuropathic pain were r and omly assigned ( 1:1 ) by block r and omisation , according to a central ised schedule , to receive two subcutaneous administrations of botulinum toxin A ( up to 300 units ) or placebo , 12 weeks apart . All patients and investigators were masked to treatment assignment . The primary outcome was the efficacy of botulinum toxin A versus placebo , measured as the change from baseline in self-reported mean weekly pain intensity over the course of 24 weeks from the first administration . The primary efficacy analysis was a mixed-model repeated- measures analysis in the intention-to-treat population . This trial is registered with Clinical Trials.gov , NCT01251211 . FINDINGS Between Oct 2 , 2010 , and Aug 2 , 2013 , 152 patients were enrolled , of whom 68 were r and omly assigned ( 34 per group ) , and 66 ( 37 [ 56 % ] men ) were included in the primary analysis ( 34 in  the botulinum toxin A group and 32 in the placebo group ) . Botulinum toxin A  reduced pain intensity over 24 weeks compared with placebo ( adjusted effect estimate -0·77 , 95 % CI -0·95 to -0·59 ; p<0·0001 ) . Pain on injection was the only adverse effect reported , and occurred in 19 ( 56 % ) participants in the botulinum toxin A group and 17 ( 53 % ) of those in the placebo group ( p=1·0 ) . Severe pain was experienced by ten ( 29 % ) participants in the botulinum toxin A group and 11 ( 34 % ) in the placebo group ( p=0·8 ) . INTERPRETATION Two administrations of botulinum toxin A , each of which comprised several injections , have a sustained analgesic effect against peripheral neuropathic pain . Several factors , such as the presence of allodynia and a limited thermal deficit , may be useful in predicting treatment response and should be investigated further . FUNDING Institut National de la Santé et de la Recherche Médicale ( INSERM ) and Fondation CNP ( France ) Summary Botulinum toxin injections to the scalene muscles did not reduce pain in subjects with thoracic outlet syndrome in this double‐blind , r and omized , controlled trial . ABSTRACT We studied the effect of botulinum toxin type A ( BTX‐A ) injections to the scalene muscles on pain in subjects with thoracic outlet syndrome ( TOS ) in this double‐blind , r and omized , parallel group trial with follow‐up at 6 weeks , 3 months , and 6 months . Thirty‐eight patients referred to physiatrists for management of TOS with BTX‐A injection were included . One subject was lost to follow‐up and all other subjects completed the trial . A 75‐unit dose of BTX‐A reconstituted with 0.75 cc of normal saline was injected to the anterior scalene ( 37.5 units ) and middle scalene ( 37.5 units ) muscles using electromyographic guidance . The primary outcome measure was pain as measured on a horizontal visual analog scale ( VAS ) 6 weeks‐post‐injection . Secondary outcomes were paresthesias measured on a VAS and function measured with the Disabilities of the Arm , Shoulder and H and ( DASH ) and Short‐form 36 ( SF‐36 ) question naires . For the primary outcome measure of VAS scores for pain at 6 weeks , the difference in the means adjusted for baseline VAS scores between placebo and BTX‐A was 5.03 mm in favor of BTX‐A ( 95 % confidence interval −15.7 to 5.7 , P = .36 ) . Changes in secondary outcome measures were also not statistically significant . We conclude that BTX‐A injections to the scalene muscles did not result in clinical ly or statistically significant improvements in pain , paresthesias , or function in this population of subjects with TOS Aim : To investigate the efficacy , safety and tolerability of intradermal and /or submucosal administration of botulinum toxin type A ( BTX-A ) for patients with trigeminal neuralgia ( TN ) . Methods : In this r and omized , double-blind , placebo-controlled study , 42 TN patients were r and omly allocated into two groups , namely , intradermal and /or submucosal injection of BTX-A ( 75 U/1.5 mL ; n = 22 ) or saline ( 1.5 mL ; n = 20 ) in the skin and /or mucosa where pain was experienced . The primary endpoints were pain severity ( assessed by the visual analogue scale ) and pain attack frequency per day . The secondary endpoint was the patient ’s overall response to treatment , assessed using the Patient Global Impression of Change scale . Patients with ≥ 50 % reduction in mean pain score at week 12 were defined as responders . Results : A total of 40 patients completed the study .  BTX-A significantly reduced pain intensity at week 2 and pain attack frequency at week 1 . The efficacy was maintained throughout the course of the study . More BTX-A treated patients reported that pain had improved by the end of the study . Significantly more responders were present in the BTX-A group ( 68.18 % ) than in the placebo group ( 15.00 % ) . BTX-A was well tolerated , with few treatment-related adverse events . Conclusions : BTX-A may be an efficient , safe and novel strategy for TN treatment OBJECTIVE We conducted a pilot trial to assess the effect of botulinum toxin B on  palmar pain and discomfort in carpal tunnel syndrome ( CTS ) patients . Design . R and omized , double-blind , placebo-controlled . PATIENTS Twenty ambulatory CTS patients . Intervention . Botulinum toxin B or placebo injections into three hypothenar muscles anatomically linked or attached to the carpal tunnel and its tentorium , that is , the Opponens Digiti Minimi and Flexor Digiti Minimi , located with electromyography ( EMG ) , and the Palmaris Brevis Muscle , anatomically located without EMG . SETTING New York City hospital . OUTCOME MEASURES Outcomes were measured with numeric ratings , with higher scores indicating worse outcomes . Daily , subjects recorded their 0 - 10 numeric ratings of overall pain levels and pain-related sleep disturbances . During weekly telephone calls , they reported their 0 - 10 ratings for overall pain , pain-related sleep disturbance , and CTS-related tingling during the night and day as experienced over the preceding 24 hours . For each of four clinic visits , we averaged each subject 's ratings of nine quality of life indicators from the West Haven-Yale Multidimensional Pain Inventory ( WHYMPI ) , each measured on a 0 - 6 numeric scale . RESULTS Over the 13-week trial , compared to baseline scores , the following outcomes predominantly showed decreases of statistical significance ( P < or = 0.050 ) or borderline significance ( 0.050 < P < or = 0.10 ) for weeks 2 through 8 : overall pain per daily diary entries and per weekly telephone reports , and pain-related sleep disturbance in the placebo group per phone report and in the botulinum toxin B group per diary report . CTS painful night tingling and day tingling , as well as the average scores of the WHYMPI quality of life indicators , showed improvements with statistical or borderline significance for almost each follow-up week . Between-group analyses , however , demonstrated that at each follow-up week , there was no statistically significant difference between the two study groups regarding changes from baseline in any study outcome . CONCLUSION Botulinum toxin B is not dramatically superior to placebo for the relief of CTS symptoms . Possible explanations of the improvements in each study group are explored Objective Botulinum toxin type A ( Botox ) injection has been used to manage pain . However , it remains to be proved whether Botox injection is effective to relieve residual limb pain ( RLP ) and phantom limb pain ( PLP ) . Design R and omized , double-blinded pilot study . Setting Medical College and an outpatient clinic in Department of Physical Medicine and Rehabilitation . Participants Amputees ( n=14 ) with intractable RLP and /or PLP who failed in the conventional treatments . Interventions Study amputees were r and omized to receive 1 Botox injection versus the combination of Lidocaine and Depomedrol injection . Each patient was evaluated at baseline and every month after the injection for 6 months . Main Outcome MeasureThe changes of RLP and PLP as recorded by VAS , and the changes of the pressure pain tolerance as determined by a pressure algometer . Results All patients completed the protocol treatment without acute side effects , and monthly assessment s of RLP , PLP , and pain tolerance after the treatment . The time trend in the outcomes was modeled as an immediate change owing to the treatment followed by a linear tread afterward . Repeated measures were incorporated using mixed effects modeling . We found that both Botox and Lidocaine/Depomedrol injections result ed in immediate improvements of RLP  ( Botox : P=0.002 ; Lidocaine/Depomedrol : P=0.06 ) and pain tolerance  ( Botox : P=0.01 ; Lidocaine/Depomedrol : P=0.07 ) . The treatment effect lasted for 6 months in both groups . The patients who received Botox injection had higher starting pain than those who received Lidocaine/Depomedrol injection ( P=0.07 ) . However , there were no statistical differences in RLP and pain tolerance between these 2 groups . In addition , no improvement of PLP was observed after Botox or Lidocaine/Depomedrol injection . Conclusions Both Botox and Lidocaine/Depomedrol injections result ed in immediate improvement of RLP ( not PLP ) and pain tolerance , which lasted for 6 months in amputees who failed in conventional treatments INTRODUCTION Piriformis syndrome is entrapment of the sciatic nerve by the piriformis muscle . METHODS In this article we describe a 56-person r and omized , double-blind , controlled study involving physical therapy and incobotulinum toxin A or placebo .  Inclusion criteria were 3-SD delay of posterior tibial ( PT ) or fibular ( FN ) H-reflexes on flexion , adduction , and internal rotation ( FAIR ) testing , and normal paraspinal electromyographic findings . Outcome measures included adverse side effects , visual analog scale ( VAS ) findings , and H-reflex delay on the FAIR test . RESULTS Mean intervention VAS score decreased significantly more compared with placebo at 2 , 4 , 6 , 8 , 10 , and 12 weeks post-injection ( P < 0.0001 ) . FAIR test scores for PT , but not FN , decreased significantly more compared with placebo at 2 , 4 , 6 , and 8 weeks post-injection ( PT : P = 0.038 , 0.003 , 0.003 , and 0.046 ) . Adverse effects were minimal . VAS slope and PT FAIR test results varied significantly ( P < 0.0001 ) . CONCLUSION Incobotulinum toxin A chemodenervation may be useful for treating piriformis syndrome as identified by the FAIR test . Muscle Nerve 56 : 258 - 263 , 2017 Abstract A double-blind , r and omized , placebo-controlled study of patients with essential trigeminal neuralgia and treatment with a single injection of onabotulinum toxin A ( BTX )  was carried out . The efficacy , safety , and tolerability of either 1 mL 0.9 % saline plus 50 U of BTX or only 1 mL of 0.9 % saline injected subcutaneously in the affected area were evaluated . Cases 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 . Pain was assessed with the visual analog scale ( VAS ) . Twenty subjects were administered BTX , and 16 subjects received placebo .  Two months after the intervention , a trend to statistical significance was observed for the VAS mean values in subjects treated with BTX and those who received placebo ( VAS 4.9 vs 6.63 , t test , P = 0.07 ) . Three months after the injection , significant differences were observed in the average VAS score for subjects treated with BTX and those treated with placebo ( VAS 4.75 vs 6.94 , respectively ; t test , P = 0.01 ) . Onabotulinum toxin A was well tolerated and seems to be a safe and useful therapy for patients with essential trigeminal neuralgia OBJECTIVE To assess the benefits of subcutaneous injection of botulinum toxin A ( BTX-A ) for the treatment of postherpetic neuralgia ( PHN ) . DESIGN We investigated the therapeutic benefits of BTX-A in subjects with PHN in a r and omized , double-blind , placebo-controlled study . Sixty subjects with PHN were r and omly and evenly distributed into BTX-A , lidocaine , and placebo groups . MEASURES After r and omization , one of the following solutions was injected subcutaneously in the affected dermatome : 5u/mL BTX-A , 0.5 % lidocaine , or 0.9 % saline ( placebo ) .  Visual analog scale ( VAS ) pain and sleeping time ( hours ) were evaluated at the time of pretreatment , day 1 , day 7 , and 3 months posttreatment . Opioid usage was calculated at day 7 and 3 months posttreatment . RESULTS Compared with pretreatment , VAS pain scores decreased at day 7 and 3 months posttreatment in all three groups ( P<0.01 ) . However , the VAS pain scores of the BTX-A group decreased more significantly compared with lidocaine and placebo groups at day 7 and 3 months posttreatment ( P<0.01 ) . Sleep time ( hours ) had improved at day 7 and at 3 months compared with pretreatment in all three groups , but the BTX-A group improved more significantly compared with lidocaine and placebo groups ( P<0.01 ) . The percent of subjects using opioids posttreatment in the BTX-A group was the lowest ( 21.1 % ) compared with the lidocaine ( 52.6 % ) and placebo ( 66.7 % ) groups ( P<0.01 ) . CONCLUSIONS Subcutaneous administration of BTX-A significantly decreased pain in PHN and reduced opioid use compared with lidocaine and placebo at day 7 and 3 months post-treatment . It also increased subjects ' sleep times OBJECTIVE To determine the efficacy of occipital nerve blocks using reconstituted botulinum toxin type-A ( BTX-A ) in providing significant and prolonged pain relief in chronic occipital neuralgia . BACKGROUND Occipital neuralgia is a unilateral or bilateral radiating pain with paresthesias commonly manifesting as paroxysmal episodes and involving the occipital and parietal regions . Common causes of occipital neuralgia include irritation or injury to the divisions of the occipital nerve , myofascial spasm , and focal entrapment of the occipital nerve . Treatment options include medication therapy , occipital nerve blocks , and surgical techniques . BTX-A , which has shown promise in relief of other headache types , may prove a viable therapeutic option for occipital neuralgia pain . METHODS Botulinum toxin type-A ( reconstituted in 3 cc of saline ) was injected into regions traversed by the greater and lesser occipital nerve in 6 subjects diagnosed with occipital neuralgia . Subjects were instructed to report their daily pain level ( on a visual analog pain scale ) , their ability to perform daily activities ( on several quality of life instruments ) and their daily pain medication usage ( based on a self-reported log ) , 2 weeks prior to the injection therapy and 12 weeks following injection therapy . Data were analyzed for significant variation from baseline values . RESULTS The dull/aching and pin/needles types of pain reported by the subjects did not show a statistically significant improvement during the trial period . The sharp/shooting type of pain , however , showed improvement during most of the trial period except weeks 3 - 4 and 5 - 6 . The quality of life measures exhibited some improvement . The headache-specific quality of life measure showed significant improvement by 6 weeks which continued through week 12 . The general health- and depression-related measures showed no statistical improvement . No significant reduction in pain medication usage was demonstrated . CONCLUSIONS Our results indicate that BTX-A improved the sharp/shooting type of pain most commonly known to be associated with occipital neuralgia . Additionally , the quality of life measures assessing burden and long-term impact of the headaches , further corroborated improvement seen in daily head pain
target: Conclusion Based on the current evidence , BTX-A may be an effective and safe option for the treatment of neuralgia .
background: Aim This meta- analysis was performed to evaluate the efficacy and safety of botulinum toxin-A ( BTX-A ) for the treatment of neuralgia .