Efficacy of botulinum toxin type A for treatment of persistent myofascial TMD pain: a randomized, controlled, double-blind multicenter study

Evidence of an effect by botulinum toxins is still lacking for most pain conditions. In the present randomized, placebo-controlled, crossover multicenter study, the efficacy of botulinum toxin type A (BTX-A) was investigated in patients with persistent myofascial temporomandibular disorders (TMD). Twenty-one patients with myofascial TMD without adequate pain relief after conventional treatment participated. A total of 50 U of BTX-A or isotonic saline (control) was randomly injected into 3 standardized sites of the painful masseter muscles. Follow-up was performed after 1 and 3 months, followed by a 1-month washout period, after which crossover occurred. Pain intensity at rest was the primary outcome measure, while physical and emotional function, global improvement, side effects, and clinical measures were additional outcome measures. There was no main difference between drugs (ANOVA; P = .163), but there was a significant time effect (P < .001), so BTX-A reduced mean (SD) percent change of pain intensity by 30 (33%) after 1 month and by 23 (30%) after 3 months compared to 11 (40%) and 4 (33%) for saline. The number of patients who received a 30% pain reduction was not significantly larger for BTX-A than after saline at any follow-up visit. The number needed to treat was 11 after 1 month and 7 after 3 months. There were no significant changes after treatment in any other outcome measures, with the exception of pain on palpation, which decreased 3 months after saline injection (P < .05). These results do not indicate a clinical relevant effect of BTX-A in patients with persistent myofascial TMD pain.     

Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial

The analgesic effectiveness and adverse effect incidence of a daily dose of 10 or 20 mg of oral methadone were evaluated in 18 patients with a diverse range of chronic neuropathic pain syndromes, who had all responded poorly to traditional analgesic regimens. Analgesia was seen after each dose of methadone. As compared with placebo, the 20 mg daily dose (given as 10 mg bd) resulted in statistically significant (P = 0.013-0.020) improvements in patient Visual Analogue Scale ratings of maximum pain intensity, average pain intensity and pain relief, recorded at the same time daily. The analgesic effects extended over 48 hours, as shown by statistically significant (P = 0.013-0.020) improvements in all three outcomes on the rest days instituted between each daily dose. Analgesic effects (lowered maximum pain intensity and increased pain relief, on the day of dosing only) were also seen when the lower daily dose of 10 mg methadone (given as 5 mg bd) was used, but these failed to reach statistical significance (P = 0.064 and 0.065, respectively). Interpatient analysis showed that the analgesic effects were not restricted to any particular type of neuropathic pain. Patient compliance was high throughout the trial. One patient withdrew during the 10 mg and six during the 20 mg methadone treatment periods. This is the first double-blind randomized controlled trial to demonstrate that methadone has an analgesic effect in neuropathic pain.     

Botulinum toxin injection for management of thoracic outlet syndrome: a double-blind, randomized, controlled trial

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, randomized, 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 Hand (DASH) and Short-form 36 (SF-36) questionnaires. 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 clinically or statistically significant improvements in pain, paresthesias, or function in this population of subjects with TOS.     

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

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 randomized, 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 randomized 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 graded 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.     

Far-infrared ray patches relieve pain and improve skin sensitivity in myofascial pain syndrome: A double-blind randomized controlled study

ObjectiveMyofascial pain syndrome (MPS) is a common disorder characterized by muscle pain if myofascial trigger points (MTrP) are stimulated. This study evaluated the effectiveness of far-infrared ray (FIR) patches in reducing the severity of pain in patients with MPS.MethodsA double-blind, randomized controlled study involving 125 patients with MPS and 201 MTrPs located in the trapezius muscle. A FIR patch was applied to 98 MTrPs for 24 h in the intervention group (61 patients) and a placebo patch was applied to 91 MTrPs in the control group (57 patients) at the end. Pain intensity was measured using the visual analogue scale (V) while pressure pain threshold (P) and maximal pain tolerance (T) were measured using an algometer before and after treatment.ResultsThe mean age of the patients was 37.16 years old and 67% were female. There was a positive correlation between P and T (p < 0.001). Older Age was associated with higher P and T due to poor skin sensitivity (p < 0.001). V improved significantly in both groups to a similar extent, but only in the intervention group, P and T decreased significantly (which implied better skin sensitivity) (p < 0.05). P and T decreased the most in the female group aged over 35, probably due to thinner skin in this subgroup.ConclusionsFIR and placebo patches were equally effective at relieving pain (with decreased V), but P and T dropped only in the intervention group with FIR patches. This probably resulted from FIR penetrated only to the skin layer and improved skin sensitivity with more blood circulation, but the muscle remained unaffected. Further studies should investigate the effect of longer exposure or higher energy applications.     

Associated reactions after stroke: a randomized controlled trial of the effect of botulinum toxin type A.

OBJECTIVE: To measure the impact of botulinum toxin A on associated reactions in patients following stroke. DESIGN: Randomized placebo-controlled trial. PATIENTS: Forty patients with spasticity in their paretic arm (median time since stroke: 2.7 years) were randomized to botulinum toxin A (Dysport; 1000 mouse units (MU) divided between elbow, wrist and finger flexors) or placebo. METHODS: Associated reactions were measured using hand dynamometry. The effort used was measured using maximum voluntary grip in the unaffected arm. Measurements were recorded at 2 pre-treatment and 3 post-intervention times. Activities that patients felt caused associated reactions and activities that were affected by associated reactions were recorded. RESULTS: Peak associated reactions force was reduced at week 6 with botulinum toxin A compared with placebo (mean group difference 19.0 N; 95% confidence interval (CI): 7.2, 30.9; p < 0.01) and week 2 (p = 0.005), with the effect wearing off by week 12 (p = 0.09). Thirty-one patients noted associated reactions on a regular basis and 24 said that these movements interfered with daily activities. Ten of 12 patients receiving botulinum toxin A and 2 of 12 receiving placebo reported reduction in interference with daily activities (p = 0.02). CONCLUSION: Botulinum toxin A reduces associated reactions and may be a useful adjunct to other rehabilitation interventions. The impact of associated reactions on daily activities may also be reduced.     

Treatment of pain attributed to plantar fasciitis with botulinum toxin a: a short-term, randomized, placebo-controlled, double-blind study

OBJECTIVE: To investigate the effect of botulinum toxin A on associated pain and functional impairment of refractory plantar fasciitis. DESIGN: This is a randomized, double-blind, placebo-controlled study of 27 patients (43 feet) with plantar fasciitis. Block randomization was performed using computer software. In patients with bilateral symptoms of comparable severity, botulinum toxin A was injected in one foot and saline in the other foot. The treatment group received a total of 70 units of botulinum toxin A divided into two sites per foot. One of the two sites was the tender area in the medial aspect of the heel close to the calcaneal tuberosity (40 units), and the other was in the arch of the foot between an inch anterior to the heel and middle of the foot (30 units). The placebo group received the same volume of normal saline. Main outcome measures included: Pain Visual Analog Scale, Maryland Foot Score, Pain Relief Visual Analog Scale, and pressure algometry response. Patients were assessed before injection, at 3 wks, and at 8 wks. RESULTS: The study revealed statistically significant changes in the treatment group. Compared with placebo injections, the botulinum toxin A group improved in all measures: Pain Visual Analog Scale (P < 0.005), Maryland Foot Score (P = 0.001), Pain Relief Visual Analog Scale (P < 0.0005), and pressure algometry response (P = 0.003). No side effects were noted. CONCLUSIONS: Botulinum toxin A injection for plantar fasciitis yields significant improvements in pain relief and overall foot function at both 3 and 8 wks after treatment.     

Sublingual buprenorphine for acute renal colic pain management: a double-blind, randomized controlled trial

Background

The aim of this study was to compare the efficacy and safety of sublingual buprenorphine with intravenous morphine sulfate for acute renal colic in the emergency department.

Methods

In this double-dummy, randomized controlled trial, we enrolled patients aged 18 to 55 years who had a clinical diagnosis of acute renal colic. Patients received either 2 mg sublingual buprenorphine with an IV placebo, or 0.1 mg/kg IV morphine sulfate with a sublingual placebo. Subjects graded their pain with a standard 11-point numeric rating scale (NRS) before medication administration and 20 and 40 minutes after that. The need for rescue analgesia and occurrence of side effects were also recorded in the two groups.

Results

Of 69 patients analyzed, 37 had received buprenorphine, and 32 had taken morphine. Baseline characteristics were similar in both groups. NRS pain scores were reduced across time by administration of both buprenorphine (from 9.8 to 5.22 and then 2.30) and morphine (from 9.78 to 4.25 and then 1.8), significantly (P <0.0001). The two regimens did not differ significantly for pain reduction (P?=?0.260). Dizziness was more frequently reported by the buprenorphine group (62.1% versus 37.5%, P <0.05) but other adverse effects observed within 40 minutes were similar in the two groups.

Conclusions

Sublingual buprenorphine (2 mg) is as effective as morphine sulfate (0.1 mg/kg) in acute renal colic pain management.     

A comparative trial of botulinum toxin type A and methylprednisolone for the treatment of myofascial pain syndrome and pain from chronic muscle spasm

Myofascial pain syndrome (MPS) is a common illness, characterised by acute or chronic focal pain, muscle stiffness and fatigue. The pathophysiology of MPS remains unclear. Previous preliminary studies have demonstrated therapeutic efficacy of the muscle relaxant botulinum toxin type A (BTX-A) in the treatment of MPS. A single-centre, randomised trial compared the effects of BTX-A with the steroid methylprednisolone (both administered intramuscularly with 0.5% bupivacaine), in 40 patients suffering from chronic myofascial pain in the piriformis, iliopsoas or scalenus anterior muscles. Thirty days after receiving an injection of either BTX-A or steroid followed by post-injection physiotherapy, pain severity had decreased significantly from baseline in both treatment groups, with no significant difference between the two treatment groups. However, the baseline pain score was significantly higher in the BTX-A treatment group compared with the steroid group (7.9 vs. 7.3), and the reduction in pain score between baseline and 30 days post-injection was greater in the BTX-A group compared with the steroid group (-3.9 vs. -3.5; P=0.06). At 60 days post-injection, the pain severity score for the BTX-A-treated patients was statistically significantly lower than the pain score for the steroid-treated population (2.3 vs. 4.9). Furthermore, the reduction in pain score in the BTX-A group at 60 days post-injection was greater than at 30 days (-5.5 vs. -3.9), whereas the effect of the steroid had begun to wane. These results indicate the superior efficacy of BTX-A over conventional steroid treatment in patients suffering from MPS, when combined with appropriate physiotherapy.     

Radiofrequency treatment relieves chronic knee osteoarthritis pain: a double-blind randomized controlled trial

Chronic osteoarthritis (OA) pain of the knee is often not effectively managed with current non-pharmacological or pharmacological treatments. Radiofrequency (RF) neurotomy is a therapeutic alternative for chronic pain. We investigated whether RF neurotomy applied to articular nerve branches (genicular nerves) was effective in relieving chronic OA knee joint pain. The study involved 38 elderly patients with (a) severe knee OA pain lasting more than 3 months, (b) positive response to a diagnostic genicular nerve block and (c) no response to conservative treatments. Patients were randomly assigned to receive percutaneous RF genicular neurotomy under fluoroscopic guidance (RF group; n = 19) or the same procedure without effective neurotomy (control group; n = 19). Visual analogue scale (VAS), Oxford knee scores, and global perceived effect on a 7-point scale were measured at baseline and at 1, 4, and 12 weeks post-procedure. VAS scores showed that the RF group had less knee joint pain at 4 (p < 0.001) and 12 (p < 0.001) weeks compared with the control group. Oxford knee scores showed similar findings (p < 0.001). In the RF group, 10/17 (59%), 11/17 (65%) and 10/17 (59%) achieved at least 50% knee pain relief at 1, 4, and 12 weeks, respectively. No patient reported a post-procedure adverse event during the follow-up period. RF neurotomy of genicular nerves leads to significant pain reduction and functional improvement in a subset of elderly chronic knee OA pain, and thus may be an effective treatment in such cases. Further trials with larger sample size and longer follow-up are warranted.     

Randomized controlled trial of botulinum toxin A for chronic myogenous orofacial pain

The purpose of this study was to determine whether botulinum toxin A (BTX-A) was efficacious for the treatment of chronic moderate to severe jaw muscle pain in females. This was a randomized double-blind, placebo-controlled crossover trial of BTX-A. Twenty five units injected into each temporalis muscle and 50 U injected into each masseter muscle using three sites per muscle with 0.2 cm(3) per site. Data were collected at baseline, 8, 16, 24 weeks, with crossover occurring at 16 weeks. Primary outcome variables were pain intensity and unpleasantness, measured by horizontal visual analog scale (VAS). Secondary outcome variables were maximum interincisal opening without and irrespective of pain, muscle palpation tenderness (12 points), and four general questions. Fifteen female patients were enrolled (18-45 years), but only ten completed the trial. Of those who finished, no statistically significant difference was found in pain intensity (P=0.10), unpleasantness (P=0.40), palpation muscle tenderness (P=0.91), or the three general questions (P=0.64, P=0.66, P=0.67). Statistical significance was achieved for maximum opening without pain (P=0.02) and irrespective of pain (P=0.005) with the BTX-A arm having a relative decreased opening. No statistically significant difference was observed in any outcome measures except maximum opening, which showed BTX-A patient opening less wide than placebo. The results do not support the use of BTX-A in the treatment of moderate to severe jaw muscle pain in this patient population.     

Comparison of superficial and deep acupuncture in the treatment of lumbar myofascial pain: a double-blind randomized controlled study

OBJECTIVE: The aim of the study was to compare the therapeutic effect of the superficial and in-depth insertion of acupuncture needles in the treatment of patients with chronic lumbar myofascial pain. DESIGN: A prospective randomized double-blind study of superficial and deep acupuncture was conducted. SETTING: The study was conducted in the Pain Service Unit of the University of Padova. PATIENTS: The study comprised 42 patients with lumbar myofascial pain who were divided into two equal groups (A and B). INTERVENTION: In group A, the needle was introduced in the skin at a depth of 2 mm, whereas in group B the needle was placed deeply into muscular tissue. The treatment was planned for a cycle of eight sessions. OUTCOME MEASURES: The intensity of pain was evaluated with the McGill Pain Questionnaire before and after treatment and at the 3-month follow-up examination. RESULTS: Although at the end of the treatment there was no evidence of significant statistical differences between the two different groups, pain reduction was greater in the group treated with deep acupuncture. A statistical difference existed between the two groups at the 3-month follow up, with a better result in the deeply stimulated group. CONCLUSIONS: Clinical results show that deep stimulation has a better analgesic effect when compared with superficial stimulation.     

Efficacy and safety of a single botulinum type A toxin complex treatment (Dysport) for the relief of upper back myofascial pain syndrome: results from a randomized double-blind placebo-controlled multicentre study

Botulinum type A toxin (BoNT-A) has antinociceptive and muscle-relaxant properties and may help relieve the symptoms of myofascial pain syndrome. In this study we evaluated the efficacy and tolerability of BoNT-A (Dysport) in patients with myofascial pain syndrome of the upper back. We conducted a prospective, randomized, double-blind, placebo-controlled, 12-week, multicentre study. Patients with moderate-to-severe myofascial pain syndrome affecting cervical and/or shoulder muscles (10 trigger points, disease duration 6-24 months) were randomized to Dysport or saline. Injections were made into the 10 most tender trigger points (40 units per site). The primary outcome was the proportion of patients with mild or no pain at week 5. Secondary outcomes included changes in pain intensity and the number of pain-free days per week. Tolerability and safety were also assessed. At week 5, significantly more patients in the Dysport group reported mild or no pain (51%), compared with the patients in the placebo group (26%; p=0.002). Compared with placebo, Dysport resulted in a significantly greater change from baseline in pain intensity during weeks 5-8 (p<0.05), and significantly fewer days per week without pain between weeks 5 and 12 (p=0.036). Treatment was well tolerated, with most side effects resolving within 8 weeks. In conclusion, in patients with upper back myofascial pain syndrome, injections of 400 Ipsen units of Dysport at 10 individualised trigger points significantly improved pain levels 4-6 weeks after treatment. Injections were well tolerated.     

Hand heating lowers postprandial blood glucose concentrations: A double-blind randomized controlled crossover trial

ObjectivesExamine effect of single hand heating with and without negative pressure on fasting blood glucose (FBG) and postprandial blood glucose (PBG).DesignDouble-blind randomized controlled trial with crossover design.SubjectsFBG experiment: 17 healthy subjects (4 males). PBG experiment: 13 healthy subjects (1 males).InterventionsDevices included one providing heat only, one heat and negative pressure, and one acting as a sham. For the FBG experiment the devices were used for 30 min. For the PBG experiment the devices were used for one hour during an oral glucose tolerance test (OGTT).Outcome MeasuresBlood glucose measurements were used to determine change in FBG, peak PBG, area under the curve (AUC), and incremental AUC (iAUC).ResultsTemperature: Change in tympanic temperature was ≤ 0.15 °C for all trials. FBG: There was no effect on FBG. PBG: Compared to the sham device the heat plus vacuum and heat only device lowered peak blood glucose by 16(31)mg/dL, p = 0.092 and 18(28)mg/dL, p = 0.039, respectively. AUC and iAUC: Compared to the sham device, the heat plus vacuum device and heat only device lowered the AUC by 5.1(15.0)%, p = 0.234 and 7.9(11.1)%, p = 0.024 respectively and iAUC by 17.2(43.4)%, p = 0.178 and 20.5(34.5)%, p = 0.054, respectively.ConclusionsHeating a single hand lowers postprandial blood glucose in healthy subjects.     

AAIR versus DDDR pacing in the bradycardia tachycardia syndrome: a prospective, randomized, double-blind, crossover trial

In 19 patients paced and medicated for bradycardia tachycardia syndrome (BTS), AAIR and DDDR pacing were compared with regard to quality of life (QoL), atrial tachyarrhythmia (AFib), exercise tolerance, and left ventricular (LV)function. Patients had a PQ interval < or = 240 ms during sinus rhythm, no second or third degree AV block, no bundle branch block, or bifascicular block. In DDDR mode, AV delay was optimized using the aortic time velocity integral. After 3 months, QoL was assessed by questionnaires, patients were investigated by 24-hour Holter, cardiopulmonary exercise testing (CPX) was performed, and LV function was determined by echocardiography. QoL was similar in all dimensions, except dizziness, showing a significantly lower prevalence in AAIR mode. The incidence of AFib was 12 episodes in 2 patients with AAIR versus 22 episodes in 7 patients with DDDR pacing (P = 0.072). In AAIR mode, 164 events of second and third degree AV block were detected in 7 patients (37%) with pauses between 1 and 4 seconds. During CPX, exercise duration and work load were higher in AAIR than in DDDR mode (423+/-127 vs 402+/-102 s and 103+/-31 vs 96+/-27 Watt, P < 0.05). Oxygen consumption (VO2), was similar in both modes. During echocardiography, only deceleration of early diastolic flow velocity and early diastolic closure rate of the anterior mitral valve leaflet were higher in DDD than in AAI pacing (5.16+/-1.35 vs 3.56+/-0.95 m/s2 and 69.2+/-23 vs 54.1+/-26 mm/s, P < 0.05). As preferred pacing mode, 11 patients chose DDDR, 8 patients chose AAIR. Hence, AAIR and DDDR pacing seem to be equally effective in BTS patients. In view of a considerable rate of high degree AV block during AAIR pacing, DDDR mode should be preferred for safety reasons.     

The effect of a polynutrient supplement on fatigue and physical activity of patients with chronic fatigue syndrome: a double-blind randomized controlled trial

BACKGROUND:The efficacy of dietary supplements in chronic fatigue syndrome (CFS) is uncertain, with conflicting evidence. Aim: To assess the effect of a polynutrient supplement on fatigue and physical activity of patients with CFS. DESIGN:Prospective randomized placebo-controlled, double-blind trial. METHODS:Fifty-three patients (16 males, 37 females) fulfilling the CDC criteria of CFS. The entry criteria were a score on the Checklist Individual Strength subscale fatigue severity (CIS fatigue) >or=40 and a weighted sum score of >or=750 for the eight subscales of the Sickness Impact Profile (SIP8) and no use of nutritional supplements in the 4 weeks prior to entry. The exclusion criteria were pregnancy and lactose intolerance. The intervention-a polynutrient supplement containing several vitamins, minerals and (co)enzymes, or placebo, twice daily for 10 weeks-was preceded by 2 weeks of baseline measurements. Outcome measurements took place in week 9 and 10 of the intervention. Five participants dropped out (4 supplement, 1 placebo). The main outcome measures were CIS fatigue score, number of CDC symptoms and SIP8 score. Efficacy analyses were performed on an intention-to-treat basis. RESULTS:No significant differences were found between the placebo and the treated group on any of the outcome measures: CIS fatigue +2.16 (95%CI -4.3 to +4.39, p=0.984); CDC symptoms +0.42 (95%CI -0.61 to +1.46, p=0.417); SIP8 +182 (95%CI -165 to +529, p=0.297). No patient reported full recovery. DISCUSSION:The findings do not support the use of a broad-spectrum nutritional supplement in treating CFS-related symptoms.