Clinical application of Botulinum toxin type-A in pain: where we are now

M Relja. Medical School, Department of Neurology, KBC Kispaticeva 12, Zagreb 10000, Croatia

BACKGROUND: Local injections of Botulinum toxin type-A (BTX-A) has become established as treatment for hyperactive muscles disorders (focal dystonia). BTX-A was also found to reduce several chronic pain states associated with muscular overactivity but also some chronic pain condition not associated with muscular disorders like neuropathic pain. 17 months after approval of BTX-A for migraine treatment it appears that if the treatment works for the migraine patients it provides significant benefit. But there are still responders and not responders to BTX-A treatment. Conflicting results have been reported to date and the mechanism of BTX-A in preventing migraine headache attacks remains controversial. Thus, there is an unmet need for identifying a predictive factor that will identify responders from non-responders. Quantitative sensory testing (QST) of cutaneous allodynia (CA) should be investigated

OBJECTIVE: To identify the classic migraine symptoms that would differentiate responders from non-responders to BTX-A treatment in episodic migraine patients. Could quantitative sensory testing (QST) of cutaneous allodynia (CA) be used.

DESIGN/METHODS: Seventy patients with episodic migraine, according to the current criteria of the HIS, (after signing written informed consent) were enrolled in a randomized, double-blind, placebo-controlled, cross-over study of 8 months duration. Patients had to be 18-65 years of age and to suffer from migraine with an average frequency of two to five attacks per month and without any prophylactic treatment at least 6 preceding months. Other type of headache (tension-type) were allowed up to 5 days per month. Patients were divided into 2 groups according to presence of cutaneous allodynia assessed by QST. Both groups were injected at baseline and after 4 months with BTX-A (as Botox, Alllergan, total dose 80 U) and/or placebo (saline) in frontal and cervical muscles. Patients kept a home diary. The primary efficacy parameters were migraine frequency, days with headache, and pain intensity. Secondary efficacy parameters were QST and the reduction of the total doses of acute anti-migraine drugs. Patients experiencing a >70 % reduction in attacks frequency within 4 months of treatment were considered as responders.

RESULTS: A total of 30 patients with CA were included in group A, and 40 patients without CA were included in group B. No significant difference was found in age, gender and the classical migraine symptoms between groups. However, there was one clear difference between the 2 groups. Group A (patients with CA) reported significant reduction (P<0.01) of migraine frequency and number of headache days during BTX-A treatment compared to placebo. Total doses of acute anti-migraine drugs was also significantly reduced (p<0.05). There was no difference in group B (patients without CA) between treatment periods (BTX-A or placebo).

CONCLUSIONS: Patients with CA are highly associated with significant prevention of migraine attacks using BTX-A treatment. This indicates that CA, as a marker of central sensitization, could be a predictive factor for responders and non-responders to BTX-A prophylactic therapy in migraine. In addition, investigation of BTX-A action on migraine on experimental models are needed.