Neck pain in chronic whiplash syndrome treated with botulinum toxin. A double-blind, placebo-controlled clinical trial.

OBJECTIVES: Neck pain in chronic whiplash syndrome is a major burden for patients, healthcare providers and insurance companies. Randomized data on treatment of botulinum toxin in chronic whiplash syndrome are scarce. We conducted a randomized, placebo-controlled clinical trial to prove efficacy of botulinum toxin for neck pain in chronic whiplash syndrome. METHODS: 40 patients with chronic whiplash syndrome (whiplash associated disorders grade 1 and 2) were randomly assigned to receive botulinum toxin (maximum 100 units) or placebo (saline) in muscles with increased tenderness. RESULTS: After 12 weeks there was no significant difference between the two treatment groups in decrease of neck pain intensity on VAS (-7.0 mm, 95% confidence interval (CI) [-20.7 to +6.7]), mean number of neck pain days (-1%; 95% CI [-15% to +13%]), neck pain hours per day (-0.14; 95% CI [-3.0 to +2.7]), days on which symptomatic treatment was taken (-0.7%; 95% CI [-15% to +13%]) number of analgesics taken per day (-0.14; 95% CI [-0.6 to +0.4]) and total cervical range of motion (-11 degrees; 95% CI [-40 to +17]). There also was no significant difference in patient's assessment of improvement after week 4, 8 and 12. CONCLUSIONS: Botulinum toxin was not proven effective in treatment of neck pain in chronic whiplash syndrome. Increased muscle tenderness alone might not be the major cause of neck pain in whiplash syndrome.

Treatment of chronic tension-type headache with botulinum toxin: a double-blind, placebo-controlled clinical trial.

Botulinum toxin is increasingly advocated as effective treatment in chronic tension-type headache. We conducted a randomized, placebo-controlled clinical trial to prove efficacy of botulinum toxin in chronic tension-type headache. Patients were randomly assigned to receive botulinum toxin (maximum 100 units) or placebo (saline) in muscles with increased tenderness. After 12 weeks there was no significant difference between the two treatment groups in decrease of headache intensity on VAS (-3.5 mm, 95% confidence interval (CI) - 20 to +13), mean number of headache days (-7%; 95% CI - 20 to +4), headache hours per day (-1.4%; 95% CI - 3.9 to +1.1), days on which symptomatic treatment was taken (-1.9%; 95% CI - 11 to +7) and number of analgesics taken per day (-0.01; 95% CI -0.25-0.22). There was no significant difference in patient's assessment of improvement after week 4, 8 and 12. Botulinum toxin was not proven effective in treatment of chronic tension-type headache. Increased muscle tenderness might not be as important in pathophysiology of chronic tension-type headache as hitherto believed.

In vivo analysis of end-plate noise of human extensor digitorum brevis muscle after intramuscularly injected botulinum toxin type A.

To evaluate changes occurring in the neuromuscular junction after injection with botulinum neurotoxin type A (BoTx), three healthy volunteers were injected with 10 U BoTx in the right extensor digitorum brevis muscle. In agreement with previous observations, amplitude of compound muscle action potential (CMAP) decreased to approximately 30% of the initial value at approximately day 8 and slowly returned to baseline values around day 250. Values of the acetylcholine receptor (AChR) open time were determined by spectral analysis of end-plate noise and from single exponential fits to the decay phase of individual miniature end-plate potentials (MEPPs). At baseline, the mean channel open times determined by end-plate noise analysis and the exponential fits were 1.1 +/- 0.2 ms and 1.20 +/- 0.04 ms, respectively. After BoTx injection, initially no end-plate noise could be recorded. From day 9 onwards, however, a gradual recurrence of end-plate noise was observed, with mean channel open times of approximately 2-5 ms, being maximal between days 20 to 140. In addition, the shape of many recorded MEPPs was different from the typical fast rising MEPPs observed at baseline. After day 80, end-plate noise gradually returned to normal and mean channel open times decreased slowly to baseline values. Our findings reflect the changed AChR characteristics of newly formed neuromuscular junctions, which are created after BoTx injection and gradually removed after restoration of the original neuromuscular junctions.