***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: & NA ; Nerve growth factor ( NGF ) modulates sensitivity and sprouting of nociceptors . We explored the spatial and temporal sensitization induced by NGF injection ( 1 & mgr;g ) in human skin . Hyperalgesia was investigated in 16 volunteers ( 36 ± 9 years ) at day 1 , 3 , 7 , 21 , and 49 . Areas of mechanical ( brush , pin‐prick ) and heat ( 43 ° C ) sensitization were mapped and thermal ( heat and cold ) pain thresholds , mechanical ( impact stimulation ) and electrically evoked pain , and axon reflex flare were assessed . No spontaneous pain or local inflammation was recorded upon NGF injection and during 49 days . Sensitization to heat was maximum at day 3 and lasted 21 days . Hyperalgesia to cold was recorded at day 7 and 21 . Hypersensitivity to mechanical impact stimuli developed delayed , reached maximum at day 21 , and persisted throughout 49 days . Fifty percent of all volunteers reported a static allodynia to tonic pressure until day 21 . Electrical stimulation at 7.5 mA was more painful at the NGF site at day 21 , which correlated significantly to maximum impact pain . Axon reflex flare was unaffected by NGF .  Sensitization was limited to the NGF injection site , no touch‐ or pin‐prick evoked secondary hyperalgesia was observed . Spatially restricted hyperalgesia indicates a peripheral rather than central mechanism . The temporal profile of lasting nociceptor sensitization suggests an altered peripheral axonal expression of sensory proteins specifically leading to mechanical and thermal sensitization . Intradermal NGF administration provokes a pattern of sensitization that can be used as experimental model for neuropathic pain PURPOSE In this r and omized , double-blind , placebo controlled phase 2 study we investigated tanezumab , a humanized monoclonal antibody that specifically inhibits nerve growth factor as a treatment for interstitial cystitis pain . MATERIAL S AND METHODS Patients with interstitial cystitis received a single intravenous dose of 200 μg/kg tanezumab or placebo . Patients recorded daily pain scores ( on an 11-point numerical rating scale ) 7 days before attending study visits and completed a urinary symptom diary for 3 of those days . Patients also completed the Interstitial Cystitis Symptom Index question naire and a global response assessment . The primary end point was change in average daily numerical rating scale pain score from baseline to week 6 . Secondary end points included global response assessment , Interstitial Cystitis Symptom Index score , micturition and urgency episode frequency per 24 hours , and mean voided volume per micturition . The incidence of adverse events was also assessed . RESULTS A total of 34 patients received tanezumab and 30 received placebo . At week 6 tanezumab produced a significant reduction from baseline in average daily pain score  vs placebo ( treatment difference [ LS mean , 90 % CI ] was -1.4 [ -2.2 , -0.5 ] ) . A significantly higher proportion of patients on tanezumab responded as improved in the global response assessment and tanezumab also significantly reduced urgency episode frequency  vs placebo . Tanezumab had no significant effect on Interstitial Cystitis Symptom Index score , micturition frequency or mean voided volume per micturition . The most common adverse events were headache  ( tanezumab 20.6 % , placebo 16.7 % ) and paresthesia  ( tanezumab 17.6 % , placebo 3.3 % ) . CONCLUSIONS Tanezumab has shown preliminary efficacy in the treatment of pain associated with interstitial cystitis Background There are no proven therapies that modify the structural changes associated with osteoarthritis ( OA ) . Pre clinical data suggests that intra-articular recombinant human BMP-7 ( bone morphogenetic protein-7 ) has reparative effects on cartilage , as well as on symptoms of joint pain . The objective of this study was to determine the safety and tolerability as well as dose-limiting toxicity and maximal tolerated dose of intra-articular BMP-7 . The secondary objectives were to determine the effect on symptomatic responses through 24 weeks . Methods This was a Phase 1 , double-blind , r and omized , multi-center , placebo-controlled , single-dose escalation safety study consisting of 4 dosing cohorts in participants with knee OA . Each cohort was to consist of 8 treated participants , with treatment allocation in a 3:1 active ( intra-articular BMP-7 ) to placebo ratio . Eligible participants were persons with symptomatic radiographic knee OA over the age of 40 . The primary objective of this study was to determine the safety and tolerability of BMP-7 including laboratory assessment s , immunogenicity data and radiographic assessment s. Secondary objectives were to determine the proportion of participants with a 20 % , 50 % , and 70 % improvement in the WOMAC pain and function subscales at 4 , 8 , 12 , and 24 weeks . Other secondary outcomes included the change from baseline to 4 , 8 , 12 , and 24 weeks for the OARSI responder criteria . Results The mean age of participants was 60 years and 73 % were female . All 33 participants who were enrolled completed the study and most adverse events were mild or moderate and were similar in placebo and BMP-7 groups . The 1 mg BMP-7 group showed a higher frequency of injection site pain and there was no ectopic bone formation seen on plain x-rays . By week 12 , most participants in both the BMP-7 and placebo groups experienced a 20 % improvement in pain and overall the BMP-7 group was similar to placebo with regard to this measurement . In the participants who received 0.1 mg and 0.3 mg BMP-7 , there was a trend toward greater symptomatic improvement than placebo . The other secondary endpoints showed similar trends including the OARSI responder criteria for which the BMP-7 groups had more responders than placebo . Conclusions There was no dose limiting toxicity identified in this study . The suggestion of a symptom response , together with the lack of dose limiting toxicity provide further support for the continued development of this product for the treatment of osteoarthritis Background . Degenerative disc disease may cause severe low-back pain , a large public health problem with significant economic and life quality impact . Chronic cases often require surgery , which may lead to biomechanical problems and accelerated degeneration of the adjacent segments . Cell-based therapies may circumvent these problems and have exhibited encouraging results in vitro and in animal studies . We design ed a pilot study to assess feasibility and safety and to obtain early indications on efficacy of treatment with mesenchymal stem cells ( MSC ) in humans . Methods . Ten patients with chronic back pain diagnosed with lumbar disc degeneration with intact annulus fibrosus were treated with autologous exp and ed bone marrow MSC injected into the nucleus pulposus area . Clinical evolution was followed for 1 year and included evaluation of back pain , disability , and quality of life . Magnetic resonance imaging measurements of disc height and fluid content were also performed . Results . Feasibility and safety were confirmed and strong indications of clinical efficacy identified . Patients exhibited rapid improvement of pain and disability ( 85 % of maximum in 3 months ) that approached 71 % of optimal efficacy . This outcome compares favorably with the results of other procedures such as spinal fusion or total disc replacement . Although disc height was not recovered , water content was significantly elevated at 12 months . Conclusions . MSC therapy may be a valid alternative treatment for  chronic back pain caused by degenerative disc disease . Advantages over current gold st and ards include simpler and more conservative intervention without surgery , preservation of normal biomechanics , and same or better pain relief Study Design . A critical appraisal of the literature . Objectives . To increase awareness of the importance of applicability and clinical relevance of the results of r and omized controlled trials ( RCTs ) in the field of spinal disorders by formulating a list of items for assessment of applicability and clinical relevance of results of RCTs . Summary of Background Data . In systematic review s of r and omized controlled trials ( RCTs ) , critical appraisal of method ologic quality is considered important . Less attention has been paid to the assessment of the applicability and the clinical relevance of the results . Methods . RCTs in an up date of the Cochrane review on  exercise therapy for low back pain were used . Most of the trials did not score positively on the five Cochrane Back Review Group basic items describing patients : intervention and setting , outcome , effect size , and benefits related to adverse effects . Item 1 was met by 88 % of the trials , but item 2 only by 51 % , item 3 by 67 % , item 4 by 35 % , and item 5 by 0 % . Subsequently , a more comprehensive list of items for the assessment of applicability and clinical relevance of results of RCTs was developed . These criteria were pilot tested on the RCTs . After pilot testing and a subsequent consensus meeting , the list of items was drafted and circulated among the members of the Editorial Board of the Cochrane Back Review Group . Changes were made in response to comments . Results . The final list consists of 40 items . The items are ordered on two headings : Does the report enable the assessment of applicability ? Are the study results clinical ly relevant ? We present examples of informative and noninformative reporting of RCTs in order to illustrate how information on applicability and clinical relevance of results can be assessed . Conclusions . Authors of RCTs should adequately report on items that are essential to assess the applicability and clinical relevance of results . The presented list of items may help clinicians reading RCTs and authors of systematic review s to draw more balanced conclusions on applicability and clinical relevance of results BACKGROUND In this era of escalating health care costs and the question able effectiveness of multiple interventions , cost effectiveness or cost utility analysis has become the cornerstone of evidence -based medicine , and has an influence coverage decisions . Even though multiple cost effectiveness analysis studies have been performed over the years , extensive literature is lacking for interventional techniques . Cost utility analysis studies of epidural injections for managing chronic low back pain demonstrated highly variable results including a lack of cost utility in r and omized trials and contrasting results in observational studies . There has not been any cost utility analysis studies of epidural injections in large r and omized trials performed in interventional pain management setting s. OBJECTIVES To assess the cost utility of caudal epidural injections in managing chronic low back pain secondary to lumbar disc herniation , axial or discogenic low back pain , lumbar central spinal stenosis , and lumbar post surgery syndrome . STUDY DESIGN This analysis is based on 4 previously published r and omized trials . SETTING A private , specialty referral interventional pain management center in the United States . METHODS Four r and omized trials were conducted assessing the clinical effectiveness of caudal epidural injections with or without steroids for lumbar disc herniation , lumbar discogenic or axial low back pain , lumbar central spinal stenosis , and post surgery syndrome . A cost utility analysis was performed with direct payment data for a total of 480 patients over a period of 2 years from these 4 trials . Outcome included various measures with significant improvement defined as at least a 50 % improvement in pain reduction and disability status . RESULTS The results of 4 r and omized controlled trials of low back pain with 480 patients with a 2 year follow-up with the actual reimbursement data showed cost utility for one year of quality -adjusted life year ( QALY ) of $ 2,206 for disc herniation , $ 2,136 for axial or discogenic pain without disc herniation , $ 2,155 for central spinal stenosis , and $ 2,191 for post surgery syndrome . All patients showed significant improvement clinical ly and showed positive results in the cost utility analysis with an average cost per one year QALY of $ 2,172.50 for all patients and $ 1,966.03 for patients judged to be successful . The results of this assessment show a better cost utility or lower cost of managing chronic , intractable low back pain with caudal epidural injections at a QALY that is similar or lower in price than medical therapy only , physical therapy , manipulation , and surgery in most cases . LIMITATIONS The limitations of this cost utility analysis include that it is a single center evaluation , even though 480 patients were included in the analysis . Further , only the costs of interventional procedures and physician visits were included . The benefits of returning to work were not assessed . CONCLUSION This cost utility analysis of caudal epidural injections in the treatment of disc herniation , axial or discogenic low back pain , central spinal stenosis , and post surgery syndrome in the lumbar spine shows the clinical effectiveness and cost utility of these injections at less than $ 2,200 per one year of QALY Study Design . Prospect i ve , population -based cohort study . Objective . To examine whether prescription of opioids within 6 weeks of low back injury is associated with work disability at 1 year . Summary of Background Data . Factors related to early medical treatment have been little investigated as possible risk factors for development of long-term work disability among workers with back injuries . We have previously shown that about 1 of 3 of workers receive an opioid prescription early after a low back injury , and a recent study suggested that such prescriptions may increase risk for subsequent disability . Methods . We analyzed detailed data reflecting paid bills for opioids prescribed within 6 weeks of the first medical visit for a back injury among 1843 workers with lost work-time cl aims . Additional baseline measures included an injury severity rating from medical records , and demographic , psychosocial , pain , function , smoking , and alcohol measures from a worker survey 
    Output:
    
Tanezumab and anti-NGFs overall had , respectively , moderate and low evidence of overall AEs and serious AEs and a higher risk of developing neurological AEs when compared with placebo .
Although anti-NGF , specifically tanezumab , showed a low-to-moderate effect on pain relief and functional improvement , it can not be recommended for low back pain treatment .
Without more research on the pathophysiology of anti-NGFs and adverse effects , its use is not safe in the overall population .