Botulinum Toxin—A Treatment for Migraine? A Systematic Review

Scalp injection of botulinum toxin type A (BT-A) into the superficial musculature has evoked interest in the management of migraine headache. In clinical trials, prevention of migraine attacks for 3 months or more has been seen in some patients following BT-A scalp injections. In the majority of pain syndromes where BT-A is effective, inhibition of muscle spasms appears to be an important component of its activity. A direct or independent and prolonged analgesic action unrelated to skeletal muscle relaxation is believed to underlie the prophylactic efficacy of BT-A in migraine; peripheral and central modulation of pain impulses by BT-A has also been proposed. A direct peripheral antinociceptive effect was not seen in three controlled studies of BT-A in normal human volunteers. Experimental evidence for BT-A-induced analgesia in rats is suggestive but dose-dependent and lasts only 2 weeks. In migraine patients, a consistent or dose-dependent response to BT-A treatment has not been seen. Peak responses to BT-A in migraine patients are seen at 8–12 weeks, whereas BT-A-affected nerve endings in mice fully recover function between 63 and 91 days; the difference in species limits the interpretation of this dissonance. As BT-A does not normally cross the intact blood-brain barrier, meningeal nociceptors appear unlikely to be influenced by scalp injections of BT-A; the possibility of antidromic transfer of BT-A in the trigeminovascular system should be considered. The extended period for which migraine prophylaxis might be required, the antigenic and headache-provoking potential of BT-A, the inability of BT-A to affect central neuronal processes significantly, including the aura of migraine, the possible placebo effect of needling, and purely subjective outcome measures in headache studies are additional concerns in evaluating this treatment strategy. The clinical utility of BT-A has not been compared against established migraine prophylactic agents. The efficacy of BT-A in preventing migraine headache attacks remains controversial and the underlying scientific rationale is debatable.