the selective melatonin receptor agonism effect of ramelteon is useful for insomnia.1 ) here we wanted to present a refractory chronic migraine case , who had significant improvements in migraine after using ramelteon . the precipitating factors were the stress , increase in physical activities and sudden cold weather . the moderate or severe pain intensity was aggravated by or causing avoidance of increased physical activity . the residual symptom between the migraine episodes were the head tense feeling , but not achieveing headache severity . the computed tomography revealed no significant findings of other causes for headache , such as tumor or hemorrhage . she ever received many kinds of medications , such as aspirin , nonsteroidal anti - inflammatory drugs , triptans , ergots , anticonvulsants and glucocorticoids . however , the severity of migraine still remained moderate ( migraine disability assessment test [ midas ] scores , 19 ) and the associated symptoms were moderate headache , dizziness , nausea , and sensitivity to sound . the migraine also exacerbated her insomnia problems , with fragmented sleep and inadequate sleep duration as 12 hours ( insomnia severity index [ isi ] score , 23 ) . she did nt have any comorbid mental disorder except insomnia . due to the fear of abuse potential related to hypnotics after 2 weeks treatment of ramelteon 8 mg / day , her sleep duration prolonged to 45 hours with less fragmentation . in addition , her migraine severity started to decline ( midas scores , 11 ) . after 6 months of ramelteon 8 mg / day treatment , the migraine severity continued to relieve ( midas scores , 6 ) with stable sleeping quality ( isi score , 14 ) . in this case , we found significant improvements in migraine severity and insomnia after the use of ramelteon . since the patient did nt have insomnia before the first onset of migraine . therefore we could speculate that the ramelteon had significant effects in migraine in such mild prolongation of sleep duration . the melatonin might relieve the headache via the following possible mechanisms , such as anti - inflammatory effect , free radical scavenging , reduction of pro - inflammatory cytokine , membrane stabilization , nitric oxide synthase activity and dopamine release inhibition , gaba and opioid analgesia potentitation , glutamate neurotoxicity protection , neurovascular regulation,2 ) cytoprotection and antiallodynic action.3 ) the pineal gland , the primary source of serotonin and melatonin , might also play a significant role in the analgesic effect.4 ) however , the clinical trial of melatonin administration showed no significant improvements in migraine severity,5 ) which suggested the modulation of melatonin receptor might be a better option for the analgesic effects . the modulation of serotonin system by the ramelteon would also relieve the pain sensation.2 ) in addition , the chemical structure of ramelteon was similar with that of indomethacin , which is a kind of non - steroidal anti - inflammatory medicine.2 ) in the study of animal model , the antinociceptive and antiallodynic actions of melatonin have been observed in different kinds of pathways , such as intrathecally or intracerebroventricular routes . the use of ramelteon , a kind of mt1 and mt2 agonist , could also relieve the pain even lack of free radical scavenger effects.3 ) the state - of - art treatment of refractory chronic migraine also includes the ramelteon due to selective m1 receptor agonism.6 ) from the successful experience in this case , we can consider the use of ramelteon for refractory chronic migraine with insomnia .
the selective melatonin receptor agonism effect of ramelteon is useful for insomnia . 
 here we wanted to present a refractory chronic migraine case , who had significant improvements in migraine after using ramelteon . 
 the possible mechanism for the ramelteon in the migraine relief might be related to melatonin effects .