Background

Neer described subacromial impingement as a clinical condition that

produces pain in the lateral region of the deltoid, when the affected extremity is forcibly elevated while the scapula is stabilized in the standing position55_. It indicates a pathologic process between the roof and floor of the subacromial space leading to impingement of rotator cuff tendons and subacromial bursa between the humeral head and structures that make up the coracoacromial arch. The etiology for this syndrome is diverse262_{. It is one of the most common}

musculoskeletal problems leading to shoulder pain and consequent functional limitation9_.

The exact pathophysiology causing the subacromial impingement syndrome is not completely known and therefore, based on empirical evidence a wide spectrum of treatment options has been proposed263_{. These range from} conservative measures like rest, activity modification, physical therapy, anti- inflammatory drugs to surgical options like arthroscopic or open subacromial decompression and even total acromionectomy47,55,198,199,210,264_{. Although} drugs such as non-steroidal anti-inflammatories (NSAIDs) and subacromial injections of local anaesthetic or corticosteroids are among the most common treatment options in the management of subacromial impingement syndrome, their use has remained controversial owing to conflicting evidence in the literature supporting their efficacy201,211,265,266_.

Subacromial injection of corticosteroid is one of the most common non-

operative interventions for the treatment of impingement syndrome and several studies have shown it to be effective in providing symptomatic relief201,216,267_{. The} precise mechanism by which corticosteroid injections provide symptomatic relief in subacromial impingement syndrome is not well understood. Possible therapeutic mechanisms include anti-inflammatory effects, relaxation of reflex muscle spasm, influence of local tissue metabolism, pain relief, mechanical improvement, and even a placebo effect268_.

Despite the popularity of the intervention a consensus seems to exist that there has been a lack of good trials defining the scientific basis of subacromial

corticosteroid injections, and in particular quantification of its efficacy201,216,267_. More important, there are potential complications associated with subacromial corticosteroid injections and these include dermal atrophy, infection including septic arthritis and abscess, collagen necrosis and tendon weakening or

rupture219,220,269,270_{. Despite considerable research, no real alternative to}

corticosteroid has been offered for subacromial injections. If corticosteroids are effective because of their anti-inflammatory properties, there is an argument to try an alternative drug designed specifically as an anti-inflammatory, such as a NSAID, which might be a more effective therapeutic intervention without the potential complications associated with corticosteroids.

NSAIDs in general have potent analgesic and anti-inflammatory

properties, and several have been used to treat tendonitis of the rotator cuff210- 213,271-273_{. A systematic review has shown that although NSAIDs showed superior} short-term efficacy compared to placebo, there are wide variations in the type of

NSAID, the dose, frequency and mode of administration and the duration of treatment213_{. The study found no conclusive evidence in favour of a particular} NSAID with respect to efficacy or tolerability. NSAIDs are most commonly administered as an oral preparation but the tolerability of oral NSAIDs varies considerably between patients, and is frequently accompanied by severe

gastrointestinal side effects, which forces a proportion of patients to discontinue treatment213,214_{. NSAIDs are not often used for intralesional or local injection} because of insufficient data, short duration of action, local irritation and poor tolerability215_.

Tenoxicam, a NSAID belonging to the oxicam group, addresses some of these concerns. Tenoxicam is available as a long acting, water soluble

preparation for injection without irritant preservatives or emulsifying agents such as benzyl alcohol and propylene glycol, which are known to cause local irritation and sometimes necrosis215_{. Tenoxicam has been} administered as a local, intramuscular or intravenous injection and well tolerated both systemically and locally by patients215,274,275_{. Itzkowitch et} al215 _{found that periarticular injection of tenoxicam was effective in treating} rotator cuff tendinitis in a randomised placebo-controlled study.

Our aim was to conduct a double-blind randomised controlled trial to evaluate the efficacy of a single subacromial injection of NSAID in improving shoulder function and compare it to a single subacromial

Vischer276 _{conducted a review on the efficacy and tolerability of Tenoxicam. They} reviewed open studies providing initial data on the efficacy and safety, double- blind studies versus placebo to assess efficacy and comparative studies assessing different doses of Tenoxicam in comparison with reference drugs like

indomethacin, naproxen, ibuprofen, diclofenac and piroxicam. They state that the efficacy of Tenoxicam has been demonstrated in double-blind comparative studies against placebo, and dose-finding studies have found the optimal dose to be 20 mg in patients with post-operative pain, ankylosing spondylitis, acute tendinitis and rheumatoid, osteo or gouty arthritis. It was found to be well tolerated both in short-term and long-term studies. The types of side-effects encountered were mainly gastrointestinal disturbances, followed in frequency by skin rashes. All side-effects were generally mild and reversible276_{. Tenoxicam} has the advantages of high efficacy coupled with low toxicity and the

pharmacokinetic properties of extensive metabolic degradation prior to elimination and long half-life277_{. Tenoxicam has been used intra-articularly for} post-operative pain relief after knee arthroscopy and found to be effective278,279_.

Besides, locally administered tenoxicam was found to be well tolerated and effective in alleviating pain and improving shoulder mobility215_{. This study} provided evidence and established that local NSAID therapy and in particular tenoxicam is a viable treatment for impingement syndrome. It seemed

appropriate to use 20mg tenoxicam (Mobiflex, Roche, Welwyn Garden City, United Kingdom) as the preferred NSAID in the trial.

To choose the appropriate corticosteroid for the trial, we conducted a survey among the rheumatologists and the orthopaedic surgeons in our trust about their preferred drug for use as a subacromial injection. A significant majority used 40 mg of methylprednisolone (Depomedrone, Pfizer, Puurs, Belgium) along with 5 ml of 1% lignocaine, while a few used triamcinolone. No one used a NSAID for subacromial injections. Therefore, Depomedrone was chosen to represent the corticosteroid arm of the trial.