***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: BACKGROUND Calcitonin gene-related peptide ( CGRP ) is a vali date d target for the treatment of episodic migraine . Here we assess the safety , tolerability , and efficacy of TEV-48125 , a monoclonal anti-CGRP antibody , in the preventive treatment of high-frequency episodic migraine . METHODS In this multicentre , r and omised , double-blind , placebo-controlled , phase 2b study , we enrolled men and women ( aged 18 - 65 years ) from 62 sites in the USA who had migraine headaches 8 - 14 days per month . Using a r and omisation list generated by a central computerised system and an interactive web response system , we r and omly assigned patients ( 1:1:1 ; stratified by sex and use of concomitant preventive drugs ) after a 28 day run-in period to three 28 day treatment cycles of subcutaneous 225 mg TEV-48125 , 675 mg TEV-48125 , or placebo . Investigators , patients , and the funder were blinded to treatment allocation . Patients reported headache information daily using an electronic diary . Primary endpoints were change from baseline in migraine days during the third treatment cycle ( weeks 9 - 12 ) and safety and tolerability . The secondary endpoint was change relative to baseline in headache-days during weeks 9 - 12 . Efficacy endpoints were analysed for the intention-to-treat population . Safety and tolerability were analysed using descriptive statistics . This trial is registered at Clinical Trials.gov , number NCT02025556 . FINDINGS Between Jan 8 , 2014 , and Oct 15 , 2014 , we enrolled 297 participants : 104 were r and omly assigned to receive placebo  , 95 to receive 225 mg TEV-48125 , and 96 to receive 675 mg TEV-48125 . The least square mean ( LSM ) change in number of migraine-days from baseline to weeks 9 - 12 was -3.46 days ( SD 5.40 ) in the placebo group , -6.27 days ( 5.38 ) in the 225 mg dose group , and -6.09 days ( 5.22 ) in the 675 mg dose group . The LSM difference in the reduction of migraine-days between the placebo and 225 mg dose groups was -2.81 days ( 95 % CI -4.07 to -1.55 ; p<0.0001 ) , whereas the difference between the placebo and 675 mg dose group was -2.64 days ( -3.90 to -1.38 ; p<0.0001 ) . LSM differences in the reduction of headache-days were -2.63 days ( -3.91 to -1.34 ; p<0.0001 ) between the placebo group and 225 mg dose group and -2.58 days ( -3.87 to 1.30 ; p < 0.0001 ) between the placebo group and the 675 mg dose group . Adverse events occurred in 58 ( 56 % ) patients in the placebo group , 44 ( 46 % ) patients in the 225 mg dose group , and 57 ( 59 % ) patients in the 675 mg dose group ; moderate or severe adverse events were reported for 29 ( 27 % ) patients , 24 ( 25 % ) patients , and 26 ( 27 % ) patients , respectively . INTERPRETATION TEV-48125 , at doses of 225 mg and 675 mg given once every 28 days for 12 weeks , was safe , well tolerated , and effective as a preventive treatment of high-frequency episodic migraine , thus supporting advancement of the clinical development programme to phase 3 clinical trials . FUNDING Teva Pharmaceuticals Study Design . A prospect i ve analysis of patients with lumbar disc herniation ( LDH ) . Objectives . To determine the role of neuropeptides as a biochemical signature of pain states in patients with LDH . Summary of Background Data . Increases in the plasma level of neuropeptides have been reported in patients suffering from a variety of painful conditions . However , there is no such report on patients with LDH . Methods . From a total of 27 patients with a single-level LDH , blood sample s were collected before and 3 weeks after lumbar discectomy .  Plasma levels of alpha calcitonin gene-related peptide ( CGRP ) , galanin , neuropeptide Y , and substance P were determined by using enzyme-linked immunosorbent assay . The association or correlation between preoperative concentration of plasma neuropeptides and gender , patients ’ age , and VAS were analyzed statistically . Also , the concentration of plasma neuropeptides was compared before and after lumbar discectomy . Results . Preoperative plasma levels of CGRP were correlated significantly with the extent of sciatica as determined by VAS . In addition , plasma levels of CGRP and galanin significantly decreased after lumbar discectomy in line with the disappearance of pain symptoms . Conclusions . These findings indicate the role of plasma CGRP and possibly galanin as a systemic neurochemical signature of pain states in patients with LDH Chronic pain is associated with significant costs to individuals directly affected by this condition , their families , the healthcare system , and the society as a whole . This paper investigates the relationship between chronic pain and life satisfaction using a sample of around 90,000 observations from the first ten waves of the Household , Income and Labour Dynamics of Australia Survey ( HILDA ) , which is a representative survey of the Australian population that started in 2000 . We estimate the negative impact on life satisfaction and examine the persistence of the effect over multiple years . Chronic pain is associated with poor health conditions , disability , decreased participation in the labour market and lower quality of life . We calculate the compensating income variation of chronic pain , based on the measurement of chronic pain , the life satisfaction of individuals and the income of households . Panel data models with r and om and fixed effects are used to control for characteristics of individuals that do not vary over time . Further , we investigate whether individuals who experience chronic pain exhibit adaptation and recovery in life satisfaction after 3 years . Overall , we find that chronic pain has a large negative association with life satisfaction , and that the compensating income variation is substantial ( around 640 US$ per day ) OBJECTIVE To determine the levels of two sensory neuropeptides ( substance P [ SP ] and calcitonin gene-related peptide [ CGRP ] ) and two endogenous opioids ( methionine-enkephalin [ Met-Enk ] and β-endorphin [ β-End ] ) in dental pulp tissue sample s subjected to controlled orthodontic intrusive forces . MATERIAL S AND METHODS Sixteen healthy premolars were selected from eight patients who were undergoing extraction for orthodontic purpose s. Eight were r and omly used as controls , and the other eight were assigned to an experimental group ( controlled orthodontic intrusive forces applied for 24 hours ) . After this period , teeth were extracted , and pulp sample s were obtained . All sample s were processed to quantify the expression levels of SP , CGRP , Met-Enk , and β-End using commercial radioimmunoassay kits . RESULTS All sample s exhibited basal levels of both neuropeptides and endogenous opioids . After 24 hours of the intrusive stimulus , all patients reported a tolerable discomfort localized at the involved premolar . Only SP was significantly increased ( P<.05 ) . For the other molecules , no statistically significant differences were observed ( P>.05 ) ; however , they expressed important increasing trends . CONCLUSIONS The expression levels of SP and CGRP in dental pulp sample s from the experimental group support the positive correlation between the symptomatic clinical scenario and increased expression levels of neuropeptides , clarifying the role of neurogenic inflammation in early injury response BACKGROUND Data from previous studies suggest that botulinum toxin A has analgesic effects against peripheral neuropathic pain , but the quality of the evidence is low . We aim ed to assess the safety and efficacy of repeated administrations of botulinum toxin A in patients with neuropathic pain . METHODS We did a r and omised , double-blind , placebo-controlled trial at two outpatient clinics in France ( Clinical Pain Centre , Ambroise Paré Hospital , APHP , Boulogne-Billancourt , and Neurological Centre , Hôpital Dupuytren , Limoges ) and one in Brazil ( Neurological Department , Hospital das Clínicas da FMUSP , São Paulo ) . Patients aged 18 - 85 years with peripheral neuropathic pain were r and omly assigned ( 1:1 ) by block r and omisation , according to a central ised schedule , to receive two subcutaneous administrations of botulinum toxin A ( up to 300 units ) or placebo , 12 weeks apart . All patients and investigators were masked to treatment assignment . The primary outcome was the efficacy of botulinum toxin A versus placebo , measured as the change from baseline in self-reported mean weekly pain intensity over the course of 24 weeks from the first administration . The primary efficacy analysis was a mixed-model repeated- measures analysis in the intention-to-treat population . This trial is registered with Clinical Trials.gov , NCT01251211 . FINDINGS Between Oct 2 , 2010 , and Aug 2 , 2013 , 152 patients were enrolled , of whom 68 were r and omly assigned ( 34 per group ) , and 66 ( 37 [ 56 % ] men ) were included in the primary analysis ( 34 in  the botulinum toxin A group and 32 in the placebo group ) . Botulinum toxin A  reduced pain intensity over 24 weeks compared with placebo ( adjusted effect estimate -0·77 , 95 % CI -0·95 to -0·59 ; p<0·0001 ) . Pain on injection was the only adverse effect reported , and occurred in 19 ( 56 % ) participants in the botulinum toxin A group and 17 ( 53 % ) of those in the placebo group ( p=1·0 ) . Severe pain was experienced by ten ( 29 % ) participants in the botulinum toxin A group and 11 ( 34 % ) in the placebo group ( p=0·8 ) . INTERPRETATION Two administrations of botulinum toxin A , each of which comprised several injections , have a sustained analgesic effect against peripheral neuropathic pain . Several factors , such as the presence of allodynia and a limited thermal deficit , may be useful in predicting treatment response and should be investigated further . FUNDING Institut National de la Santé et de la Recherche Médicale ( INSERM ) and Fondation CNP ( France ) Calcitonin gene-related peptide ( CGRP ) has been detected in increased amounts in external jugular venous blood during migraine attacks . However , it is unknown whether this is secondary to migraine or whether CGRP may cause headache . In a double-blind crossover study , the effect of human αCGRP ( 2 μg/min ) or placebo infused intravenously for 20 min was studied in 12 patients suffering from migraine without aura . Headache intensity was scored on a scale from 0 to 10 . Two patients were excluded due to severe hypotension and one because she had an infection . In the first hour median peak headache score was 1.0 in the hαCGRP group vs. 0 in the placebo group ( P < 0.01 ) . During the following 11 h all patients experienced headaches after hαCGRP vs. one patient after placebo ( P = 0.0004 ) . The median maximal headache score was 4 after CGRP and 0 after placebo ( P = 0.006 ) . In three patients after hαCGRP , but in no patients after  placebo , the delayed headache fulfilled the IHS criteria for migraine without aura . As intravenous administration of hαCGRP  causes headache and migraine in migraineurs  , our study suggests that the increase in CGRP observed during spontaneous migraine attacks may play a causative role Neutral endopeptidase ( NEP ) and angiotensin-converting enzyme ( ACE ) are involved in neuropeptide degradation and may modulate neurogenic inflammation . We therefore explored the effect of specific blockers of NEP and ACE on the intensity of neurogenic inflammation . We investigated eight subjects on three occasions . Two pairs of microdialysis fibers equipped with intraluminal wires were inserted intracutaneously into the volar forearms and electrical stimuli were delivered via the intraluminal electrodes . The microdialysis fibers were perfused either with normal saline , phosphoramidon ( NEP inhibitor ) , or captopril ( ACE inhibitor ) . CGRP release was assessed in the microdialysis eluate via a specific EIA and by evaluating the extent and intensity of the neurogenic flare via a laser Doppler imager . The area of hyperalgesia and allodynia was assessed during electrical stimulation . Inhibition of NEP with phosphoramidon increased flare intensity ( P < 0.002 ) and size ( P < 0.01 ) , while blocking ACE had no effect on neurogenic vasodilation . CGRP release could be measured in microdialysis sample s after phosphoramidon perfusion only ( P < 0.03 ) , not in sample s with captopril or saline perfusion . No effect on the areas of hyperalgesia and allodynia could be detected . Our findings suggest that NEP but not ACE 
    Output:
    
An association between measured CGRP levels and somatic , visceral , neuropathic and inflammatory pain was found .
Increased CGRP levels were reported in plasma , synovial and cerebrospinal fluid in subjects with musculoskeletal pain .
A r and omized clinical trial on monoclonal antibody , which selectively binds to and inhibits the activity of CGRP ( galcanezumab ) in patients with osteoarthritis knee pain , failed to demonstrate improvement of pain compared with placebo .
Conclusion The present review revealed the association between measured CGRP levels and somatic , visceral , neuropathic and inflammatory pain .
These data suggest that CGRP may act as a neuromodulator in non-headache pain conditions .