***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: To investigate the role of plasma calcitonin gene-related peptide ( CGRP ) in paediatric migraine , we prospect ively collected  134 blood sample  s during or between attacks from 66 migraine , 33 non-migraine headache ( non-migraine ) and 22 non-headache patients , aged 4–18 years .  Plasma CGRP concentrations were measured by enzyme-linked immunosorbent assay and disability by Pediatric MIgraine Disability ASsessment ( PedMIDAS ) question naire . Migraineurs had higher plasma CGRP levels than non-migraine patients ( P = 0.007 ) . The attack level was higher than the non-attack level in migraine ( P = 0.036 ) , but not in non-migraine , patients . This was also revealed in paired comparison ( n = 9 , P = 0.015 vs. n = 4 , P = 0.47 ) . Using a threshold of 55.1 pg/ml , the sensitivity of the attack level in predicting migraine was 0.81 , and specificity 0.75 . The PedMIDAS score tended to be higher in the high CGRP ( > 200 pg/ml , n = 7 ) group than in the low ( < 200 pg/ml , n = 33 ) group ( 26.07 vs. 19.32 , P = 0.16 ) using Mann – Whitney test . Plasma CGRP is useful for diagnosis in paediatric migraine Interictal serum levels of serotonin and plasma and mononuclear cell concentrations of β‐endorphin were measured in 20 juvenile patients ( 13 suffering from migraine without aura and 7 from episodic tension‐type headache ) before and after 3 months of L‐5‐hydroxytryptophan treatment ( 5 mg/ kg/day ) and compared with a control group of 17 headache‐free healthy subjects Plasma levels of beta‐endorphin ( BE ) , an endogenous opioid analgesic , are often reported as they relate to acute and chronic pain outcomes . However , little is known about what resting plasma BE levels might reveal about functioning of the endogenous opioid antinociceptive system . This study directly examined associations between resting plasma BE and subsequent endogenous opioid analgesic responses to acute pain in 39 healthy controls and 37 individuals with chronic low back pain ( LBP ) .  Resting baseline levels of plasma BE were assessed . Next , participants received opioid blockade ( 8 mg naloxone i.v . ) or placebo in a double‐blind , r and omized , crossover design . Participants then underwent two acute pain stimuli : finger pressure ( FP ) pain and ischaemic ( ISC ) forearm pain . Blockade effects ( naloxone minus placebo pain ratings ) were derived to index endogenous opioid analgesic function . In placebo condition analyses for both pain stimuli , higher resting BE levels were associated with subsequently greater reported pain intensity ( p 's < 0.05 ) , with this effect occurring primarily in healthy controls ( BE × Participant Type interactions , p 's < 0.05 ) . In blockade effect analyses across both pain tasks , higher resting plasma BE predicted less subsequent endogenous opioid analgesia ( smaller blockade effects ; p 's < 0.05 ) . For the ISC task , these links were significantly more prominent in LBP participants ( BE × Participant Type Interactions , p 's < 0.05 ) . Results suggest that elevated resting plasma BE may be a potential biomarker for reduced endogenous opioid analgesic capacity , particularly among individuals with chronic pain . Potential clinical implication s are discussed & NA ; Although calcitonin gene‐related peptide ( CGRP ) has been shown to be elevated in jugular venous blood of adult migraineurs during acute migraine attacks , it remains unknown whether CGRP is increased outside of attacks in jugular or cubital venous blood . The aim of the present study was to compare interictal plasma levels of CGRP in adult migraine patients and in healthy controls . Twenty patients with a diagnosis of migraine with or without aura and 20 healthy controls were included . In blood from the cubital vein , CGRP levels were significantly higher in patients ( 75±8 pmol/l ( mean±SEM ) ) than in controls ( 49±3 pmol/l ) ( P=0.005 ) . The subgroup of patients suffering exclusively from migraine without aura ( n=14 ) also had significantly higher levels of CGRP ( 82±10 pmol/l ) than controls ( n=20 ; 49±3 pmol/l ) ( P=0.001 ) . The findings could not be explained by confounding factors such as age , sex or use of contraceptive pills . We therefore conclude that CGRP is increased in cubital venous blood of migraineurs outside of attack . It is hypothesized that this finding may reflect a long‐lasting or permanent abnormal neurogenic vascular control in patients with migraine The aim of the present study was to verify cerebrospinal fluid ( CSF ) levels of glial cell line-derived neurotrophic factor ( GDNF ) and somatostatin , both measured by sensitive immunoassay , in : 16 chronic migraine ( CM ) patients , 15 patients with an antecedent history of migraine without aura diagnosed as having probable chronic migraine ( PCM ) and probable analgesic-abuse headache ( PAAH ) , 20 patients affected by primary fibromyalgia syndrome ( PFMS ) , and 20 control subjects . Significantly lower levels of GDNF and somatostatin were found in the CSF of both CM and PCM + PAAH patients compared with controls ( GDNF = P < 0.001 , P < 0.002 ; somatostatin = P < 0.002 , P < 0.0003 ) , without significant difference between the two groups . PFMS patients , with and without analgesic abuse , also had significantly lower levels of both somatostatin and GDNF ( P < 0.0002 , P < 0.001 ) , which did not differ from those of CM and PCM + PAAH patients . A significant positive correlation emerged between CSF values of GDNF and those of somatostatin in CM ( r = 0.70 , P < 0.02 ) , PCM + PAAH ( r = 0.78 , P < 0.004 ) , and PFMS patients ( r = 0.68 , P < 0.008 ) . Based on experimental findings , it can be postulated that reduced CSF levels of GDNF and somatostatin in both CM and PCM + PAAH patients can contribute to sustained central sensitization underlying chronic head pain . The abuse of simple or combination analgesics does not seem to influence the biochemical changes investigated , which appear to be more strictly related to the chronic pain state , as demonstrated also for fibromyalgia & NA ; In nine women suffering from menstrual migraine ( MM ) , and in six healthy asymptomatic volunteers  , plasma beta‐endorphin ( beta‐EP ) , growth hormone ( GH ) , norepinephrine ( NE ) , and 3‐methoxy‐4‐hydroxyphenylethyleneglycol ( MHPG ) concentrations were measured in response to clonidine ( 0.075 mg , i.v . ) stimulation . In MM patients clonidine testing was performed in both the early and the late luteal phases of the menstrual cycle . Premenstrual symptoms were prospect ively evaluated in the actual cycle using the Moos Menstrual Distress Question naire . beta‐EP ( after gel chromatography ) and GH were measured using radioimmunoassay . NE and MHPG were evaluated by HPLC using electrochemical detection . In both phases of the menstrual cycle clonidine  significantly reduced NE and MHPG levels in MM patients and controls in a similar way . In MM patients beta‐EP and GH plasma levels were stimulated by clonidine only in the early luteal phase , whereas they remained unchanged when they were stimulated in the premenstrual period . In controls the response of both hormones was not affected by the menstrual cycle . The lack of hormonal response  to clonidine in MM may suggest a postsynaptic alpha 2‐adrenoreceptor hyposensitivity during the premenstrual period . This demonstrates a transient vulnerability of the neuroendocrine/neurovegetative systems , and could thus be a factor facilitating the precipitation of both behavioral changes and migraine attacks BACKGROUND Pharmaceuticals with calcium- or sodium-channel-blocking activity have proven useful for migraine prophylaxis , and calcium channel , sodium transporter , and sodium channel gene mutations have been found in familial hemiplegic migraine . However , it is not known whether calcium or sodium homeostasis is altered in migraine . OBJECTIVE To compare levels of sodium , calcium , potassium , and magnesium in cerebrospinal fluid ( CSF ) and blood plasma between migraineurs and controls . METHODS We recruited 20 migraineurs without aura and 11 controls prospect ively , and studied migraineurs in sick ( MH(+ ) ) and well ( MH(- ) ) states . We collected lumbar CSF and venous blood plasma , quantified elements with ion-selective electrodes or colorimetry , and determined osmolality by depression of freezing point . We compared levels of Na(+ ) , Ca(2 + ) , K(+ ) , and Mg among and also within subjects who were studied in both MH(+ ) and MH(- ) states . RESULTS Mean CSF Na(+ ) levels were increased by 3 mmol/L in MH(+ ) compared with MH(- ) and by 4 mmol/L compared to controls ( P < 0.005 ) . In 4 subjects who were sample d in both MH(+ ) and MH(- ) states , mean CSF Na(+ ) concentration increased by 2 mmol/L in the MH(+ ) state compared with the MH(- ) state ( P < 0.05 ) . Simultaneous plasma Na(+ ) levels did not differ among the 3 clinical groups , nor did osmolality , total Ca and Ca(2 + ) , K(+ ) , and total Mg levels in CSF . CONCLUSIONS Compared to both controls and the MH(- ) state , CSF Na(+ ) concentration increased in MH(+ ) independently from other clinical or pharmacological fluctuations , CSF concentrations of Ca(2 + ) , Mg , and K(+ ) , and blood plasma Na(+ ) levels . These results implicate a deviation of Na(+ ) homeostasis in migraine . The modestly elevated extracellular Na(+ ) in MH(+ ) may cause the neural changes that underlie clinical features of migraine Neurotrophins , such as brain-derived neurotrophic factor ( BDNF ) and nerve growth factor ( NGF ) , have been implicated in the generation and modulation of pain . To investigate whether alterations in neurotrophin levels can be detected in subjects suffering from nociceptive disorders , such as primary headaches , we determined the peripheral ( platelet and plasma ) levels of BDNF and NGF in patients suffering from migraine , with or without aura , or cluster headache ( CH ) , in the interictal phase , and in healthy volunteers . All primary headaches patients studied showed significantly decreased platelet levels of BDNF ( migraine vs. controls P < 0.001 ; CH vs. controls P < 0.01 ) , while a selective reduction of platelet NGF was observed in migraine sufferers and not in CH patients compared with control subjects ( migraine vs. controls P < 0.001 ) . These changes were not accompanied by significant modifications of neurotrophin plasma levels . Our findings show for the first time that changes in peripheral levels of neurotrophines ( BDNF and NGF ) occur in patients suffering from different types of primary headaches , suggesting a potential involvement of BDNF and NGF in the pathophysiology of these disorders , and raising the possibility that differences in peripheral neurotrophins may help to distinguish migraine biologically from CH 
    Output:
    
Conclusions Glutamate , β-EP , CGRP and NGF concentrations are altered in CSF and , except for NGF , also in blood of migraineurs .