Management of pain in arthritis

Management and control of pain is central to the management of all arthritis patients. An accurate assessment and an individualised approach to each patient is required. In this article we present three case studies to demonstrate this.

Rheumatoid arthritis

Case 1: A 78 year old male patient presents with progressive pain of his left knee, which is worse with use and is severely limiting his activities. He had a duodenal ulcer 15 years ago. 

Despite the availability of disease-modifying treatment, some patients with rheumatoid arthritis fail to respond adequately to treatment. Progressive, erosive joint damage can lead to significant pain, deformity and functional disability over years to decades. The optimal management of advanced rheumatoid arthritis requires an accurate assessment. If there is ongoing inflammation, therapeutic options in the form of disease-modifying antirheumatic drugs (DMARDs), biologics, etc need to be explored and maximised. 

However, the pain and reduced function from damaged joints needs to be addressed separately. This is best delivered in a multidisciplinary setting. The input of an experienced physiotherapist and occupational therapist is crucial. A home exercise programme can maintain joint range of motion and prevent further functional decline. Splints can be used to prevent or correct joint contractures and assistive devices can be provided for activities of daily living.

Analgesics may be required for pain relief. Paracetamol should be firstline. Non-steroidal anti-inflammatory drugs (NSAIDs) also have a role. However, patients with rheumatoid arthritis are twice as likely as patients with osteoarthritis to have a serious complication from NSAID treatment. The risk of cardiovascular disease is also higher, thus making NSAIDs an unsuitable choice in many patients with advanced disease. 

Tramadol has activity at the opioid ‘mu’ receptors and inhibits the reuptake of serotonin and noradrenaline. The side effect profile is similar to that of other weak opioids and includes GI upset, constipation, sedation and pruritus. Tapentadol has a similar mode of action, with the potential advantage of reduced gastrointestinal side effects.

The analgesic effect of paracetamol can be potentiated by combining it with tramadol or codeine. Concern regarding the risk of addiction is allayed by studies investigating the risk of opioid abuse; one study of 12,000 medical patients revealing only four patients without a prior history of substance abuse developed dependence on the medication. Most studies have found that all patients who developed problems with opioid use had a prior history of substance abuse.

Amitriptyline and gabapentin can also be very useful adjuncts (see below). Surgery may play an important role in the management of patients with advanced rheumatoid arthritis and can help to reduce pain and improve function. 

Osteoarthritis

Case 2: A 58 year lady with a long history of rheumatoid arthritis presents with severe pain from multiple deformities of advanced disease.

The goals of treatment of osteoarthritis (OA) are to control pain, minimise disability, improve quality of life and prevent progression of disease. Management should be individualised to each patient and can be divided into non-pharmacological and pharmacological approaches.

Educating the patient about their role in the management of OA is crucial. Weight reduction can be beneficial in improving pain in knee OA, with even modest weight loss improving joint pain and function. It can also reduce progression. A common response to the pain is to rest the affected joint and curtail activities. Resting the joint is only recommended for short periods of time, as prolonged rest can lead to muscle atrophy, thus further reducing joint mobility. It should be reserved for when patients have an acute exacerbation of symptoms and should not exceed 12 to 24 hours. Physiotherapy can be beneficial, improving function and reducing pain. Addressing the psychosocial impact of OA on a patient’s life is also critical.

At present, there are no pharmacologic therapies that can prevent the progression of osteoarthritis, although research is ongoing. If pharmacological treatment is required, paracetamol is the drug of choice, initially on an ‘as required’ basis. If symptoms persist, introduce paracetamol on a regular basis at doses of up to 3g a day. Paracetamol is generally well tolerated, with the low risk of hepatotoxicity increased in patients who abuse alcohol. 

If paracetamol is inadequate, consider stepping up treatment to combinations with codeine or tramadol or adding an NSAID. The side-effect profile and dose frequency should be considered when selecting an NSAID. Some prefer multiple doses on an ‘as required’ basis – consider ibuprofen, ketoprofen or diclofenac. Others prefer once-daily use – consider etoricoxib or meloxicam. Allow two to four weeks to evaluate efficacy. 

All NSAIDs increase the risk of cardiovascular events. Most studies agree that naproxen has the most favourable cardiovascular profile. In patients with gastrointestinal (GI) risk factors (age greater than 60, previous GI event, corticosteroid use, anticoagulation), a combination of an NSAID and proton-pump inhibitor (for example, naproxen and esomeprazole) may be used. An alternative is etoricoxib in patients without significant cardiovascular disease risk. Topical NSAIDs may provide a small but measurable benefit in people with knee OA. 

If patients continue to have disabling pain, or if NSAIDs are unsuitable, consider intra-articular glucocorticoid injection. Controlled studies demonstrate a benefit for pain relief and physical function, with superiority to placebo for a variable duration (two to three months). There is no evidence that repeated injection causes joint damage, but consensus is that a single joint should not be injected more than four times a year. At this frequency, other approaches should be considered, such as mechanical factors to be addressed by the physiotherapist or orthopaedic referral for arthroplasty. The literature is mixed with regard to injection with intra-articular hyaluronic acid. A subpopulation of patients with osteoarthritis respond well, with a longer duration of benefit versus steroid – consider it in younger patients and those without significant effusions. 

The use of glucosamine is popular but the evidence for its efficacy is inconclusive. As adverse effects are rare, a trial of glucosamine sulphate (1,500mg/day) may alleviate symptoms and allow a reduction in NSAID or other drug use over a trial six week period. 

In some patients, despite maximal medical management, symptoms persist and referral to an orthopaedic surgeon may be considered, with radiological confirmation of advanced changes before referral. 

In patients with inflammatory osteoarthritis, hydroxychloroquine can be beneficial. There are no clinical trials, the experience is largely anecdotal and the confidence in its safe use comes from the extensive experience in rheumatoid arthritis. This option should be discussed with a rheumatologist.

Generalised pain

Case 3: A 41 year old female presents with a three year history of generalised pain, fatigue and altered sleep pattern. 

Managing patients with generalised pain can be challenging. A useful mnemonic is ‘PAIN’, referring to pharmacological options, the importance of activity, the role of clear information, and a reminder that opiates should not be used. Some patients will respond well to non-pharmacological therapy. Others will require an intensive treatment plan with a multidisciplinary approach. Patient education is critical and patients need to understand that the symptoms will wax and wane, but that in general pain and fatigue persist. However, it is important to reassure patients that the majority of people with generalised pain live normal and active lives. 

Exercise can be of great benefit in this patient cohort, both in improving pain and function. It can be difficult to start and maintain an exercise programme as patients frequently believe that exercise will precipitate and/or aggravate their pain. Explaining in advance that a temporary increase in myalgia may occur can help to improve compliance. 

Pharmacological monotherapy is often required in conjunction with non-pharmacological treatment. The choice of drug depends on the individual patient. Tricyclic antidepressants are often effective. The doses required are lower than that required to treat depression and commencing amitriptyline 10-25mg at night can lead to a clinically important improvement in 25-45% of patients when compared to placebo. The dose can be increased according to response every two weeks, but doses of greater than 75mg are rarely indicated. Use can be limited by side effects (including dry mouth, drowsiness, constipation and cardiotoxicity in older patients), which can be apparent even at these low doses. 

If a patient is intolerant of or unresponsive to amitriptyline, move to second line treatment. Duloxetine can be useful if fatigue is a significant issue. Commence at 30mg in the morning and gradually increase to 60mg, which is the recommended minimum effective dose for pain reduction in fibromyalgia. Reductions in pain can occur in the first week of treatment. The most common side effects experienced are headache, nausea and dry mouth. 

In patients where sleep disturbance is prominent, try pregabalin at bedtime. Begin with a dose of 25-50mg and titrate upwards as tolerated. Trials demonstrating efficacy of pregabalin used doses of 300-600mg, at which adverse events (including dizziness, drowsiness, dry mouth, weight gain and peripheral oedema) led to discontinuation in 25% of patients. 

Many patients have continued symptoms despite the above measures and require a combination of drugs, e.g. duloxetine in the morning with a low dose of pregabalin or amitriptyline in the evening. In patients with an inadequate response to these medications or with a temporary need for an increase in treatment during an acute flare, other medications such as paracetamol, tramadol or NSAIDs may be helpful. However, the evidence base for their efficacy is limited. Assessment for a co-existent mood disorder is critical as failure to address this will lead to failure of the above therapies.