3. Discussion
extracranial, Pain, pain, allodynia, headache pain, CM, peripheral nociceptor sensitization, migraine, disease disability
MIGRAINE
This is the first randomized, double-blind, placebo-controlled study demonstrating the efficacy and safety of the “follow the origin of maximum pain” approach using subcutaneous injections of BoNT-A targeted (SjBoT) to the occipital or trigeminal skin area in non-responder patients with chronic migraine. Our results show that subcutaneous injections of BoNT-A targeted to the skin area of maximum headache pain origin significantly reduce migraine frequency, pain severity, and disease disability.The efficacy of the individualized SjBoT injection paradigm is based on the antinociceptive effect of subcutaneous injections of BoNT-A and on the targeted regional administration of BoNT-A using the “follow the origin of maximum pain” approach.Consistent with our results, several animal studies confirmed the antinociceptive effects of subcutaneous injection of botulinum toxin type A [In the context of migraine, extracranial application of BoNT-A was shown to inhibit mechanical transduction in the suture branches of meningeal nociceptors, thus inhibiting mechanical nociception in peripheral trigeminovascular neurons [Another important contributing factor to the efficacy of the SjBoT injection paradigm for the prevention of CM is the regional administration of BoNT-A in the cutaneous area of the maximum pain’s origin. The latter is the area of ictal cutaneous allodynia during migraine attack, which represents the clinical expression of peripheral nociceptor sensitization [The strength of this pilot study is intrinsically linked to its design. Another important finding is that the individualized SjBoT injections paradigm appears to be a safe treatment. The limitation is that this is a single-center study, and other limitations are due to the small number of patients, the lack of evaluation of long-term effects of repeated administration of the treatment, and the administration of a single placebo treatment. However, in view of the severity of migraine in these patients and the poor response to placebo treatment, it was appropriate to administer a single dose of placebo. Another possible limitation is that the placebo response was low compared with what was observed in the PREEMPT studies [In conclusion, the data from this study demonstrate that the “Follow the Origin of Maximum Pain” approach using the individualized SjBoT paradigm may be a useful option for the preventive treatment of CM in non-responder patients and suggests the need to do further similar studies to confirm our results.