H. Lee Moffitt Cancer Center & Research Institute

Nonnarcotic Analgesics in Short-term Pain: Musculoskeletal Disorders

Introduction

Injuries to the musculoskeletal system occurring in sports and at the workplace are becoming more commonplace and, at the same time, the severity of such injuries is increasing. The sequelae of such injuries may be complex and may encompass significant social, economic, and psychological manifestations. Patients experiencing significant pain may avoid engaging in the normal activities of daily living. Whereas at one time most occupational injuries occurred as heavy machines were being used, the advent of the computer has brought with it a new group of repetitive motion injuries. Also, the types of injuries physicians are seeing has changed because today’s workplace includes more women, senior citizens, and physically disabled workers, and each of these populations is particularly disposed to developing a relatively unique set of injuries.

Occupational and recreational injuries together appear to be the greatest cause of strains, sprains, tendonitis, and episodes of bursitis that result in short-term pain (Table).¹ Relief of pain is accomplished by means of a comprehensive therapeutic approach making use of several modalities of care. For many patients, the use of medication helps control the pain experienced and simultaneously hastens the healing of the injury.

Regional rheumatic pain syndromes include disorders involving muscles, tendons, enthesis joints, cartilage, ligaments, fascia, bone, and nerve. Many of these syndromes are the result of injury from a specific event — often an occupational or recreational activity or an accident — that may be a specific episode limited in time or may be associated with repetitive overuse of the human body. The occurrence of such syndromes may be secondary to abnormal body positions or abnormal body mechanics. In addition, older persons experience an increased incidence of injury as compared with younger individuals. The organic changes associated with such an increase include tendons that become less flexible and elastic with age and muscles that atrophy and decrease in bulk. The alteration in the structure of muscles makes them less able to absorb mechanical force, a phenomenon that can result in greater forces being transmitted to ligaments, tendons, joints, and enthesis. Furthermore, the lack of adequate stretching, disuse atrophy and genetic predisposition (hypermobility syndrome) in the elderly may lead to variation in anatomy as well as to altered biomechanics. Such variations and alterations may predispose older persons to injury and pain.²

The injuries being discussed occur most frequently in conjunction with occupational and recreational activities.³ Occupational injuries severe enough to confine a worker to bed for 24 to 48 hours number 2,779,000 annually, according to a survey conducted by the US Public Health Service.⁴ Most of these injuries are minor and include cuts, bruises, and strains of the extremities. However, more disabling injuries also may originate in the workplace; among these more serious injuries, those to the lower back and extremities predominate.⁴ Upper extremity, back, cervical spine, and repetitive stress injuries are the most frequent forms of occupational injuries, in contrast to the lower extremity injuries more commonly associated with athletic activities. Cumulative trauma disorder — which refers to tenosynovitis, carpal tunnel disorders, epicondylitis, and rotator cuff injuries as well as to such less well defined entities as diffuse back and para spinal complaints — has grown more prevalent and now accounts for more than 50% of all occupational injuries in the United States. The annual incidence of cumulative trauma disorder is 21 cases per 1,000 workers.⁵

The economic impact of short-term injuries is difficult to assess. The National Safety Council estimates that on an annual basis, 14.6 injuries occur for every 1,000 persons in the labor force. Furthermore, work-related injuries cost $45 billion per year in terms of both medical expenses and lost work time.⁵

During the past decades, Americans have placed increasing emphasis on preventive health, and this change has been accompanied by more widespread regular exercise throughout the population. In the United States, 22% of adults report that five times a week they engage in regular, sustained physical activity of greater or lesser intensity that lasts 30 minutes or more. Of these, 15% engage in regular vigorous physical activity for at least 20 minutes three times a week. Exercise has been shown to be of demonstrable value: according to the American Heart Association, 250,000 deaths a year in the United States are attributable to a lack of regular physical activity. Another striking fact is that risk of developing high blood pressure among those Americans who are less physically active is 30% to 50% greater than for those who engage in greater amounts of physical activity.⁶ An estimated 215 million Americans participate in at least one recreational sport, such as running, walking, swimming, and bowling. Among Americans 18 years of age or less, 7 million of 41 million participate in school sports.

However, whether it is adults or students who are participating in the physical activity, many of those who exercise sustain injuries. For example, the 7 million students who participate in school sports sustain approximately 10 to 12 million injuries annually.^7,8 Although injuries associated with recreational activities constitute a significant problem in both younger persons and adults, physicians and other health care professionals should encourage healthful recreational activities.

Although musculoskeletal injuries occur in many environments and while the incidence of such occupational and recreational injuries is particularly great, the impact of subpopulations on the epidemiology of these injuries remains an important consideration. Both the incidence and the character of musculoskeletal disorders, for example, are affected by the numbers of women, senior citizens, and physically disabled persons present in the work force and recreational environments. Each population subgroup is prone to a particular set of injuries and is vulnerable to certain social, economic, and psychological manifestations of disease. In addition, it is important to note that all persons who work with computers are at increased risk for developing repetitive motion injuries.

Nonsteroidal Anti-inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are traditionally prescribed for treatment of inflammation associated with chronic arthritis and treatment of soft-tissue injury. The use of NSAIDs in the management of these conditions relates to the combined analgesic, anti-inflammatory, and antipyretic properties of these medicines. In addition to treating pain, NSAIDs undoubtedly decrease soft-tissue inflammation and stiffness associated with acute injury.

Such injury causes cellular damage to the soft or connective tissues, and the damage sets the stage for inflammation. Initial vasoconstriction is followed by the release of the chemical mediators of inflammation: histamine and bradykinin are released by mast cells and thromboxane, leukotrienes, and prostaglandins are released by cell membranes.⁹ The inflammatory process is central not only to pain mechanisms, increased pain sensation being a protective device, but also to the repair process, for the chemical mediators of inflammation cause increased cellular and capillary permeability and, simultaneously, stimulate vasodilation.¹⁰ Activated white blood cells and macrophages are brought into the area of tissue damage. Erythema, heat, pain, and swelling appear.

However, dysfunction may eventually result because although the inflammatory response is essential to the resolution of the injury, excessive inflammation with edema interrupts the flow of oxygen to healthy tissues. Hypoxia results, and thus further tissue damage may occur.

NSAIDs block the formation of prostaglandins from arachidonic acid by inhibiting the generation of the enzyme cyclooxygenase as a consequence of tissue damage, a process described in Dr John Vane’s Nobel-prize-winning research.¹¹ These prostaglandins — PGD₂, PGE₂, and PGF₂ — cause dilation of blood vessels and the leakage of fluid into surrounding tissues. In conjunction with histamine, bradykinin, and other substances, these prostaglandins cause pain.

The effects of NSAIDs on cartilage are more controversial. Cartilage does not respond to injury with inflammation. Instead, the balance through which the chondrocyte is constantly synthesizing to build blocks of collagen and matrix, as well as to produce enzymes that degrade both collagen and the proteoglycan matrix, is distorted. Following acute injury, the process of degradation may gain greater prominence than that of synthesis. As a consequence, accelerated secondary osteoarthritis may develop.

Evidence of the effects of NSAIDs on cartilage is conflicting. Some studies show that salicylates and certain other NSAIDs suppress proteoglycan synthesis in normal cartilage.¹² Other studies demonstrate that NSAIDs reduce the activity of degradative enzymes in cartilage and suppress cartilage catabolism.^13,14 However, these studies were performed on uninjured cartilage and, therefore, may or may not indicate how NSAIDs function in cartilage following acute injury. In addition, researchers have not adequately studied the interesting conjecture that the cytokines involved in inflammation stimulate the chondrocyte to secrete degradative enzymes and that inhibition of inflammation thus may be chondroprotective in acute injury.

Often the initial inflammatory reaction to acute injury is in excess of that needed for healing. Therefore, it is beneficial that NSAIDs reduce soft-tissue inflammation. They achieve this by affecting the production of cytokines and super oxide radicals, the aggregation and adhesion of neutrophils, and the inhibition of prostaglandins, as well as by impacting on other mechanisms. Whether or not an NSAID should be used immediately following acute injury is controversial. Some authorities argue that because these drugs block thromboxane, their early use — within 72 hours of the injury — promotes additional bleeding and retards healing. Others contend that the rapid inhibition of the inflammatory process will diminish pain, decrease inflammation, and more quickly mobilize the patient.¹⁵ An excellent review summarizes the capabilities of NSAIDs to decrease the inflammation, pain tenderness, and stiffness associated with soft-tissue injuries.¹⁶

Whether NSAIDs can hasten a return to work or sports and can promote restoration of normal functioning following injury has not been well studied and remains controversial. Animal studies suggest that during the healing process, NSAID administration during the first six days postinjury helps to strengthen injured ligaments.¹⁷ Additional research has demonstrated that treatment with NSAIDs promotes the return of function following muscle strain.¹⁸ In contrast, other studies do not demonstrate the return of full function or improved performance when NSAIDs are used following injury.¹⁹

The growing popularity of sports and exercise in the general population has undoubtedly resulted in increased use of NSAIDs for acute injuries. Such use, combined with rest, rehabilitation, and modification of activity, decreases pain and hastens the patient’s return to normal activities.²⁰

Conclusions

The incidence and severity of acute musculoskeletal injury have increased, and many of these injuries are associated with occupational and recreational activities. Increasing numbers of women, older persons, and physically disabled persons in the workforce, as well as the large numbers of Americans who engage in recreational exercise, are important factors associated with this increase.

The use of NSAIDs for the treatment of acute soft-tissue injuries is widespread. Over 99 million prescriptions for these drugs are filled on an annual basis in the United States, in addition to over-the-counter purchase of NSAIDs.²¹ Although the clinical indications for the use of NSAIDs for the treatment of acute soft-tissue injuries has not been adequately defined,¹⁶ their effectiveness for patients with musculoskeletal complaints is clear. In combination with rest, rehabilitation, and modification of activity following acute soft-tissue injuries, NSAIDs help to provide symptomatic relief. Accumulating evidence suggests that they neither delay healing nor interfere with the repair of soft tissue or cartilage following acute injury. Furthermore, in the nongeriatric population, the use of NSAIDs as short-term therapy appears to be associated with neither short-term nor long-term side effects.

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