title: [Transdermal nitroglycerin versus corticosteroid infiltration for rotator cuff tendinitis]. Costs of shoulder pain and resource use in primary health care: a cost-of-illness study in Sweden The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Topical glyceryl trinitrate treatment of chronic patellar tendinopathy: a randomised, double-blind, placebo-controlled clinical trial Transdermal nitroglycerine treatment of shoulder tendinopathies in patients with spinal cord injuries Topical Glyceryl Trinitrate Application in the Treatment of Chronic Supraspinatus Tendinopathy Topical Nitric Oxide Application in the Treatment of Chronic Extensor Tendinosis at the Elbow Oxygen free radicals and tendon healing. Management of tennis elbow with topical glyceryl trinitrate. Successful treatment of shoulder pain syndrome due to supraspinatus tendinitis with transdermal nitroglycerin. A double blind study Topical glyceryl trinitrate treatment of chronic noninsertional achilles tendinopathy. A randomized, double-blind, placebo-controlled trial. Topical Glyceryl Trinitrate and Noninsertional Achilles Tendinopathy Randomised, double-blind, placebo-controlled clinical trial of a new topical glyceryl trinitrate patch for chronic lateral epicondylosis
abstract: AIMS To compare transdermal nitroglycerin ( NTG ) and corticosteroid infiltration in patients with rotator cuff tendinitis ( RCT ) . DESIGN Experimental , r and omized controlled study . SETTING Semirural basic health area in the Garraf region of Barcelona province , Spain , with a population of public health service users of 12000 . PATIENTS AND METHODS Patients diagnosed as having RCT of less than 6 weeks ' evolution who had not responded to treatment with oral nonsteroid antiinflammatory drugs . The patients were distributed r and omly into two groups : a ) group A , local infiltration via a posterior approach with a depot corticosteroid and local anesthesia , and b ) group B , treated for 3 days with a 5-mg NTC patch . MAIN MEASURES Age , sex , pain ( measured with an analog visual scale ) and adverse events . In patients who showed a partial response , treatment was repeated up to 3 times at 15-day intervals . Pain was tested after 7 - 10 days of treatment . Complete improvement was considered a reduction in pain of more than 5 points on the analog visual scale ; partial improvement was considered a reduction of 3 - 5 points , and treatment failure was recorded when there was no improvement in pain or when there was a decrease of less than 3 points . RESULTS A total of 48 patients were included ; 33 ( 69 % ) were women and 15 ( 31 % ) were men . Mean age was 61 years . In group A , complete improvement was seen in 19 patients and partial improvement in 3 ; treatment failed in 2 patients . In group B complete improvement was seen in 5 patients , partial improvement in 5 , and failure of treatment in 14 . The difference between groups was statistically significant . Adverse events were mild pain at the injection site in 4 patients from group A , and headache in 15 patients from group B , 8 of whom ab and oned treatment for this reason . CONCLUSION Treatment with NTG is not a clear alternative to infiltration of corticosteroids in patients with RCT , because of its lack of effectiveness and because of the greater number of patients who had adverse events that lead them to ab and on treatment Background Painful shoulders pose a substantial socioeconomic burden . A prospect i ve cost-of-illness study was performed to assess the costs associated with healthcare use and loss of productivity in patients with shoulder pain in primary health care in Sweden . Methods The study was performed in western Sweden , in a region with 24 000 inhabitants . Data were collected during six months from electronic patient records at three primary healthcare centres in two municipalities . All patients between 20 and 64 years of age who presented with shoulder pain to a general practitioner or a physiotherapist were included . Diagnostic codes were used for selection , and the cases were manually controlled . The cost for sick leave was calculated according to the human capital approach . Sensitivity analysis was used to explore uncertainty in various factors used in the model . Results 204 ( 103 women ) patients , mean age 48 ( SD 11 ) years , were registered . Half of the cases were closed within six weeks , whereas 32 patients ( 16 % ) remained in the system for more than six months . A fifth of the patients were responsible for 91 % of the total costs , and for 44 % of the healthcare costs . The mean healthcare cost per patient was € 326 ( SD 389 ) during six months . Physiotherapy treatments accounted for 60 % . The costs for sick leave contributed to 84 % of the total costs . The mean annual total cost was € 4139 per patient . Estimated costs for secondary care increased the total costs by one third . Conclusions The model applied in this study provides valuable information that can be used in cost evaluations . Costs for secondary care and particularly for sick leave have a major influence on total costs and interventions that can reduce long periods of sick leave are warranted Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objectives To assess if continuous topical glyceryl trinitrate ( GTN ) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone . Methods R and omised double-blind , placebo-controlled clinical trial comparing a 12-week programme of using a GTN or placebo patch in combination with eccentric squats on a decline board . Measurements were performed at baseline , 6 , 12 and 24 weeks . Primary outcome measure was the Victorian Institute of Sports Assessment -Patella ( VISA-P ) question naire . Secondary outcome measures were patient satisfaction and pain scores during sports . Generalised estimated equation was used to analyse the treatment , time and treatment × time effect . Analyses were performed following the intention-to-treat principle . Results VISA-P scores for both groups improved over the study period to 75.0±16.2 and 80.7±22.1 at 24 weeks . Results showed a significant effect for time ( p<0.01 ) but no effect for treatment × time ( p=0.80 ) . Mean Visual Analogue Scores pain scores during sports for both groups increased over the study period to 6.6±3 and 7.8±3.1 . Results showed a significant effect for time ( p<0.01 ) but no effect for treatment × time ( p=0.38 ) . Patient satisfaction showed no difference between GTN and placebo groups ( p=0.25 ) after 24 weeks , but did show a significant difference over time ( p=0.01 ) . Three patients in the GTN group reported some rash . Conclusion It seems that continuous topical GTN treatment in addition to an eccentric exercise programme does not improve clinical outcome compared to placebo patches and an eccentric exercise programme in patients with chronic patellar tendinopathy Study design : A clinical blind study was conducted to determine the efficacy of transdermal nitroglycerine treatment on the awareness of shoulder pain . Objective : This study aims to determine the effects of transdermal nitroglycerine on shoulder pain and on functional shoulder movement in patients with spinal cord injuries and shoulder tendinopathies . A second aim is to establish the side effects of the treatment . Setting : Hospital “ La Fe ” in Valencia , Spain . Methods : A total of 45 spinal cord injury patients , all of whom are wheelchair users with shoulder tendinopathy , were r and omly divided into two groups : placebo ( n=12 ) and experimental ( n=33 ) . The experimental group ( EG ) received transdermal treatment for 6 months in the form of a 1.25 mg nitroglycerine ( NT ) patch on the greater tubercle . A placebo patch was used with the placebo subjects . Functional shoulder movements were assessed by articular range of motion and pain , using a visual analogical scale . Results : NT treatment reduced the awareness of shoulder pain and increased the functional movement and range of articular motion in the shoulders of the EG members ( P<0.05 ) . Conclusions : We conclude that transdermal NT is an efficient method for treating shoulder tendinopathies in wheelchair users with spinal cord injuries Background Topical glyceryl trinitrate therapy has previously demonstrated short-term pain reduction in patients with supraspinatus tendinopathy . Hypothesis Topical glyceryl trinitrate improves outcome measures in patients with supraspinatus tendinopathy . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods Fifty-three patients ( 57 shoulders ) were recruited , and the authors completed a prospect i ve , r and omized , double-blinded , placebo-controlled clinical trial of continuous topical glyceryl trinitrate treatment ( 1.25 mg/24-h glyceryl trinitrate ) . Results The glyceryl trinitrate group had significantly reduced shoulder pain with activity , at night , and at rest at week 24 ( P = . 03 ) ; reduced internal rotation impingement at week 24 ( P = . 02 ) ; increased range of motion in abduction and internal rotation at week 24 ( P = . 04 ) ; and increased force at weeks 12 and 24 with supraspinatus muscle testing ( P = . 001 ) , external rotation ( P = . 04 ) , internal rotation ( P = . 01 ) , adduction ( P = . 04 ) , and subscapularis pushoff ( P = . 01 ) . Forty-six percent of patients on glyceryl trinitrate patches were asymptomatic with activities of daily living at 6 months compared with 24 % of patients with tendon rehabilitation alone ( P = . 007 , χ2 analysis ) . Mean effect size for all outcome measures was 0.26 . Discussion Topical glyceryl trinitrate treatment significantly improved pain scores , range of motion , internal rotation impingement , muscular force , and patient outcomes in patients with supraspinatus tendinopathy . Topical glyceryl trinitrate should be included as part of nonsurgical management of chronic tendinopathies Background : Extensor tendinosis ( “ tennis elbow ” ) is a degenerative overuse tendinopathy of the wrist extensors at their attachment to the lateral humeral epicondyle . No treatment has been universally successful . Topical application of nitric oxide has been used effectively to treat fractures and cutaneous wounds in animal models , presumably by stimulation of collagen synthesis in fibroblasts . Purpose : To determine whether topical nitric oxide can improve outcome of patients with extensor tendinosis . Study Design : Prospect i ve , r and omized , double-blinded clinical trial . Methods : Eighty-six patients with extensor tendinosis were r and omized into two equal groups ; both were instructed to perform a st and ard tendon rehabilitation program . One group received an active glyceryl trinitrate transdermal patch , and the other group received a placebo patch . Results : Patients in the glyceryl trinitrate group had significantly reduced elbow pain with activity at 2 weeks , reduced epicondylar tenderness at 6 and 12 weeks , and an increase in wrist extensor mean peak force and total work at 24 weeks . At 6 months , 81 % of treated patients were asymptomatic during activities of daily living , compared with 60 % of patients who had tendon rehabilitation alone . Conclusions : Application of topical nitric oxide improved early pain with activity , late functional measures , and outcomes of patients with extensor tendinosis Nitric oxide is a small free radical generated by a family of enzymes , the nitric oxide synthases ( NOSs ) . In a series of experiments performed over the last 15 years , we showed that nitric oxide is induced by all 3 isoforms of NOS during tendon healing and that it plays a crucial beneficial role in restoring tendon function . In normal tendons , very little NOS activity was found , whereas in injured rat and human tendons , NOS activity was expressed in healing fibroblasts in a temporal fashion . In healing rat Achilles tendon fibroblasts , the first isoform to be expressed was endothelial NOS , followed by inducible NOS and then brain or neuronal NOS . Systemic inhibition of NOS activity decreased the cross-sectional area and mechanical properties of the healing rodent Achilles tendons . The addition of nitric oxide via nitric oxide-flurbiprofen enhanced rat Achilles tendon healing . The addition of nitric oxide to cultured human tendon cells via chemical means and via adenoviral transfection enhanced collagen synthesis , suggesting that one mechanism for the beneficial effect of nitric oxide on tendon healing might be via matrix synthesis . Most recently , 3 r and omized , double-blind clinical trials evaluated the efficacy of nitric oxide donation via a patch in the management of the tendinopathy . In all 3 clinical trials , there was a significant positive beneficial effect of nitric oxide donation to the clinical symptoms and function of patients with Achilles tendinopathy , tennis elbow , and supraspinatus tendinitis OBJECTIVE The aim of this study was to evaluate the treatment results of the application of nitric oxide ( NO ) in the form of topical glyceryl trinitrate ( GTN ) for the treatment of lateral epicondylitis ( LE ) . METHODS The study included 40 patients with LE r and omized into 2 equal groups . Selection criteria included the presence of pain , tenderness , and positive pain stimulating maneuvers .  Glyceryl trinitrate patches were applied to the area of maximal tenderness once a day in the treatment group and placebo patches in the control group . Outcomes in terms of pain relief was assessed using the visual analog scale ( VAS ) and were evaluated according to the criteria of Verhaar et al. Excellent or good results were considered successful . Differences in VAS scores between the two groups were calculated using the Mann-Whitney U-test and the chi-square test was used to investigate distributions of categorical variables ( sex , affected side ) and good and excellent results among groups . RESULTS There were no significant differences in any of the baseline clinical parameters between groups . At the 3rd week follow-up , there were statistically significant differences in the pain measured using VAS between groups ( mean VAS score of the control and treatment groups were 6.45 and 3.15 , respectively ) ( p=0.001 ) . Patients in the GTN group and control group had lower VAS pain scores and reduced elbow pain at 3 weeks ( 3.15 vs 8.05 in the GTN and 6.45 vs 8.80 in the control group ) . In the control group , no patient had excellent or good results while 18 ( 90 % ) patients in treatment group reported successful treatment . There was statistically significant difference in the VAS measured at 6 months between groups ( mean VAS score of the control and treatment groups were 4.85 and 0.70 , respectively ) ( p=0.001 ) . CONCLUSION The administration of NO directly over an area of tendinopathy through a GTN patch reduces pain and other symptoms in chronic LE & NA ; We have conducted a prospect i ve double blind r and omized and placebo controlled clinical study in 20 patients with shoulder pain syndrome caused by supraspinatus tendinitis to determine whether transdermal nitroglycerin ( NTG ) has analgesic action in this condition . In a r and omized manner we used a 5‐mg NTG ( Nitroplast ® ) patch per day over 3 days or similar placebo patches applied in the most painful area . Patients were evaluated before treatment was initiated and after 24 and 48 h. The assessment was made blindly by the same clinical investigator . The follow‐up showed a significant decrease in intensity of pain at 24 h ( 7.05 ± 0.4 to 4.5 ± 0.5 ) and 48 h ( 2 ± 0.3 ) in the NTG group ( P < 0.003 ) . No changes were observed in the placebo group . The mean pain duration , activity of the extremity and hours of sleep also improved in the NTG group , with no significant modification in the placebo group . Two patients experienced headache as a side effect 24 h after treatment was started . Patients in the NTG group remained free of symptoms when they were assessed 15 days later . We conclude that NTG is useful in the treatment of shoulder pain syndrome caused by supraspinatus tendinitis and that this treatment could be a useful approach to the management of this common disturbance and probably also in other tendon musculoskeletal disorders BACKGROUND Noninsertional Achilles tendinopathy is a degenerative overuse disorder . No method has been universally successful in treating this condition . Topically applied nitric oxide has been shown , in animal models , to be effective for the treatment of fractures and cutaneous wounds through mechanisms that may include stimulation of collagen synthesis in fibroblasts . The goal of the present study was to determine if topical glyceryl trinitrate improves clinical outcome measures in patients with Achilles tendinopathy . METHODS A prospect i ve , r and omized , double-blind , placebo-controlled trial involving a total of sixty-five patients ( eighty-four Achilles tendons ) was performed to compare continuous application of topical glyceryl trinitrate ( at a dosage of 1.25 mg per twenty-four hours ) with rehabilitation alone for the treatment of noninsertional Achilles tendinopathy . RESULTS Compared with the control group , the glyceryl trinitrate group showed reduced pain with activity at twelve weeks ( p = 0.02 ) and twenty-four weeks ( p = 0.03 ) , reduced night pain at twelve weeks ( p = 0.04 ) , reduced tenderness at twelve weeks ( p = 0.02 ) , decreased pain scores after the hop test at twenty-four weeks ( p = 0.005 ) , and increased ankle plantar flexor mean total work compared with the baseline level at twenty-four weeks ( p = 0.04 ) . Twenty-eight ( 78 % ) of thirty-six tendons in the glyceryl trinitrate group were asymptomatic with activities of daily living at six months , compared with twenty ( 49 % ) of forty-one tendons in the placebo group ( p = 0.001 , chi-square analysis ) . The mean effect size for all outcome measures was 0.14 . CONCLUSIONS Topical glyceryl trinitrate significantly reduced pain with activity and at night , improved functional measures , and improved outcomes in patients with Achilles tendinopathy Background Topical glyceryl trinitrate ( GTN ) therapy has been advocated in the treatment of Achilles tendinopathy . The mechanism of action is unknown but may be related to modulation of local nitric oxide levels . Hypothesis Topical GTN therapy for noninsertional Achilles tendinopathy will significantly enhance clinical improvement and will be associated with increased collagen synthesis within the tendon . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods Forty patients were recruited . Twenty underwent  st and ard nonoperative physical therapy  , and 20 underwent physical therapy and topical GTN daily . Clinical outcome was assessed using the Ankle Osteoarthritis Scale ( AOS ) visual analog score . Patients who failed to improve with conservative measures and who underwent surgical decompression had histological and immunohistochemical examination of sample s from the Achilles tendon . Results Glyceryl trinitrate did not offer any additional clinical benefit over st and ard nonoperative treatment for noninsertional Achilles tendinopathy . After 6 months of treatment , there was no significant difference in scores between the groups for pain ( 3.0 vs 3.1 , P = .42 ) or disability ( 2.15 vs 2.25 , P = .38 ) . Histological examination did not show any difference in neovascularization , collagen synthesis , or stimulated fibroblasts between the 2 groups . There was no evidence of modulation of nitric oxide synthase , a marker of nitric oxide production , in those tendons treated with GTN . Conclusion and Clinical Relevance This study has failed to support the clinical benefit of GTN patches previously described in the literature . In the available tissue sample s , there did not appear to be any histological or immunohistochemical change in Achilles tendinopathy treated with GTN compared with those undergoing st and ard nonoperative therapy Objective : This study aim ed to determine whether a new glyceryl trinitrate patch preparation is effective in treating chronic lateral epicondylosis . Design : R and omised double-blind controlled clinical trial . Setting : Private practice patients : 154 adult patients with chronic lateral epicondylosis were recruited , with 136 patients completing the trial . Interventions : 8 weeks of glyceryl trinitrate patch application ( dosages of 72 mg/24 h , 1.44 mg/24 h , and 3.6 mg/24 h ) , or placebo patch application . Main outcome measures : Subjective global assessment of change in elbow symptoms , patient-rated tennis elbow evaluation , visual analogue pain at rest , visual analogue pain with activity , visual analogue pain intensity , grip strength , and strength testing using the Orthopaedic Research Institute-Tennis Elbow Testing System . Results : At 8 weeks there was a significant decrease in elbow pain with activity in the glyceryl trinitrate 0.72 mg/24 h group compared with placebo ( p = 0.04 ) . There were no other significant differences . Conclusions : Continuous 1.25 mg/24 h topical glyceryl trinitrate treatment , when combined with daily exercise rehabilitation , has previously demonstrated efficacy in treating chronic lateral epicondylosis . There was significantly decreased elbow pain with activity at 8 weeks in the glyceryl trinitrate 0.72 mg/24 h group ( p = 0.04 ) . This short-term dose-ranging study did not demonstrate a treatment effect of a new topical glyceryl trinitrate patch in dosages of 1.44 mg/24 h or 3.6 mg/24 h , which conflicts with previous studies on topical glyceryl trinitrate treatment . Trial registration number : NCT00447928
target: For all tendinopathies , improvements in pain were significant when comparing GTN versus placebo in the short term ( < 8 weeks ; poor evidence ) .
  Significant improvements in midterm outcomes for treatment with GTN versus placebo included the following : patient satisfaction ( strong evidence ) ; chances of being asymptomatic with activities of daily living ( strong evidence ) ; range of movement ( moderate evidence ) ; strength ( moderate evidence ) ; pain ( at night and with activity ; poor evidence ) and local tenderness ( poor evidence ) .
  Patients treated with topical GTN reported a higher incidence of headaches than those who received placebo ( moderate evidence ) .
  Conclusions and relevance Treatment of tendinopathies with topical GTN for up to 6 months appears to be superior to placebo and may therefore be a useful adjunct to the treating healthcare professions
background: Objective To produce a best evidence synthesis of the clinical effects of topical glyceryl trinitrate ( GTN ) in the treatment of tendinopathies .