According to the European guidelines for management of acute nonspecific back pain in primary care, LBP (also known as lumbosacral pain) is “pain and discomfort, localized below the costal margin and above the inferior gluteal folds, with or without leg pain”.4
LBP is often categorized by duration of symptoms first, and next by putative etiology. Acute LBP generally lasts less than 6 weeks, subacute LBP lasts 6–12 weeks, and chronic LBP lasts longer than 12 weeks.1
Etiologically, “nonspecific LBP” comprises symptoms not attributable to a known condition (eg, infection, tumor, osteoporosis, ankylosing spondylitis, fracture, inflammatory process, radicular syndrome, or cauda equina syndrome). “Recurrent LBP” is defined as a new episode of LBP after a symptom-free period of 6 months, whereas recurrence in less than 6 months is considered as exacerbation of chronic LBP. Within the category of acute LBP, there is sometimes a very brief “hyperacute” period of 24–48 hours during which symptom intensity is so great that sufferers are essentially immobilized, and motion is prevented by pain and intense spasm. Fortunately, this hyperacute LBP is seen in a minority of patients, and generally resolves within 24–48 hours.
The time categorization of LBP is more than academic, in that it is also predictive of prognosis: a high percentage of individuals who progress to chronic LBP will incur long-term disability, with its concomitant economic disadvantages, unemployment, and need for ongoing involvement with the health care system.
LBP is amongst the top ten problems presenting in primary care, whether the population be young adult or senior citizen.1
The lifetime prevalence of LBP is 70%–90% in industrialized countries, and the one-year prevalence is 15%–45%.5
The peak prevalence occurs between the ages of 35 and 55 years. The adult incidence is 5% per year.4
Despite the commonplace presentation of LBP, clinicians may feel some uncertainty regarding optimal symptomatic management.
The natural history of acute LBP indicates that, even in the absence of treatment, up to 70% of acute LBP cases are resolved within 3 weeks, and up to 90% by 12 weeks.6
Unfortunately, 2%–7% of acute LBP cases develop chronic pain, accounting for up to 75%–85% of total worker absenteeism.13
The most common risk factors for LBP are previous LBP, heavy physical work (frequent bending, twisting, lifting, pulling, pushing) sedentary lifestyle, workplace vibrations, psychosocial risk factors (stress, distress, anxiety, depression, cognitive functioning, pain behavior), job dissatisfaction, mental stress at work, smoking, obesity, and lack of exercise.4
The clinician’s task is to exclude the red flags (like age at onset of pain <20 or >55 years, weight loss, neurologic changes, significant trauma, or chest pain), inform the patient of the generally benign nature of the disorder, encourage physical activity, and reduce pain to enhance mobility, allowing maximum opportunity for return to work as quickly as possible. NSAIDs are one of the pharmacotherapeutic tools which can be used during this process.
Nonsteroidal anti-inflammatory drugs
It appears that NSAIDs have been used to manage musculoskeletal symptoms since antiquity. Although sodium salicylate (a derivative of various plants, such as willow bark), was probably the first NSAID, gastrointestinal side effects precluded its widespread use. Subsequently, the creation of aspirin in 1897 by means of adding acetic acid to sodium salicylate (invented by chemist Felix Hoffman of the German Friedrich Bayer and Company) allowed for a more tolerable NSAID.14
Most patients presenting to the clinician with LBP will have two primary agendas, ie, ascertaining whether important secondary pathology is present (eg, neoplasia, infection, abdominal aortic aneurysm), and relief of pain.15
The main clinical goals in the management of acute LBP is to reduce pain, improve mobility, and physical function. NSAIDs are often considered front-line agents because they act rapidly and are generally well tolerated. Cyclo-oxygenase 2 enzyme (Cox-2) inhibitors have some advantage over the Cox-1 inhibitors in terms of safety. Indeed, the majority of patients are likely to have already tried one or more over-the-counter remedies, which may include NSAIDs.16
The primary mechanism of action of NSAIDs is blockade of conversion of arachidonic acid to inflammatory prostaglandins, although an impact upon leukotriene production may also play a role.17
Cox-2 is the primary pathway through which arachidonic acid is converted into inflammatory prostaglandins, which can produce pain. Hence, interruption of this pathway, an activity common to all NSAIDs (including aspirin) is believed to be the basis of pain relief. Cox-2 is generally believed to be an “inducible enzyme”, ie, in the absence of stimuli such as inflammation, Cox-2 is inactive. Cox-2 is also involved in maintenance of renal glomerular flow. Accordingly, when glomerular flow is dependent upon activity of Cox-2 to induce vasodilation, any agent which blocks Cox-2 may result in reduced glomerular flow, with a subsequent increase in sodium, potassium, and water retention, as well as an increase in blood urea nitrogen and creatinine.
Endoscopy studies indicate that up to 15%–30% of persons on chronic NSAID treatment demonstrate erosions or ulcers.18
Unfortunately, symptoms are not an accurate guide to the presence, absence, or severity of gastrointestinal pathology induced by NSAIDs. Even when serious upper gastrointestinal bleeding occurs, it is asymptomatic in the majority of persons until a bleeding event is evident. Hence, clinicians cannot rely upon reports of gastrointestinal tolerability to inform whether gastrointestinal toxicity from NSAIDs is occurring.
The burden of toxicity from NSAIDs belies what had been the widely held perspective that NSAIDs are “safer” analgesics. Both Cox-1 and Cox-2 inhibitors have adverse drug reactions in both the short term and the long term. Indeed, it has been reported that as many as 107,000 hospitalizations and 16,500 deaths annually in the United States may be attributable to NSAID toxicity.19
Through the 1990s it was suggested that for every dollar spent on NSAIDs, treatment of NSAID toxicity cost $1.25.20
Similarly, in the United Kingdom, 10,000 hospital admissions and 2000 deaths annually have been attributed to NSAIDs.21
Cox-1 appears to be critical in the maintenance of gastrointestinal mucosal integrity. The promise of Cox-2 selective inhibitors was based upon the belief that because the therapeutic effects (analgesic and anti-inflammatory) of NSAIDs reside in Cox-2 inhibition, and most of the toxic effects are a result of Cox-1 inhibition, agents which only impact Cox-2 might be free of meaningful adverse gastrointestinal effects.
This understanding, although fundamentally sound, turned out to be only partially correct. First, all cyclo-oxygenase selectivity is relative. That is, Cox-2 selective agents have a high relative degree of blockade of Cox-2, while they incur small (but not zero) Cox-1 effects. Additionally, Cox selectivity may be a dose-related phenomenon, and may also vary depending upon the assay used to assess Cox activity. For instance, in the United States, etodolac (Lodine®
) and meloxicam (Mobic®
) are considered “traditional” (ie, not Cox-2 specific) NSAIDs. In Canada and much of Europe, meloxicam (in particular) was considered a Cox-2 selective agent, based upon the William Harvey human modified whole blood assay.22
In keeping with the above, analysis of various NSAIDs by this method at the time indicated that, at 80% inhibition of Cox-2, rofecoxib, etodolac, and meloxicam were the three most selective NSAIDs tested (all were more Cox-2 selective than the currently available agent, celecoxib). However, even with the most selective agents, some degree of Cox-1 inhibition occurs.16
Finally, populations who tend to use NSAIDs commonly or chronically are often of advanced years, and subsequently are also using aspirin long term for the primary or secondary prevention of cardiovascular disease. It has been shown that concomitant administration of aspirin with NSAIDs elevates the risk of gastrointestinal bleeding by 3–4-fold.