Many athletes have promoted a culture of acceptance regarding pain and sport. “No pain, no gain” resonates in athletic venues worldwide. Although some exertion-related soreness is to be expected, there also is a degree of pain that is abnormal when attributed to exercise. Pain may be a sign of injury that if ignored or masked by analgesics could lead to worsening of the root condition. To some extent, the perception of pain is an evolutionary adaptation to prompt the injured to take time for rest and allow for healing.
In recent years, television commercials have touted the use of various over-the-counter (OTC) and prescription medications for treating pain. Many people of all activity levels take widely available analgesics in response to pain resulting from athletic activity. The general acceptance of exercise coexisting with pain has led to regular use of medications, prescribed or not, to alleviate physical activity-related pain, especially when related to acute injury. A survey of 563 National Collegiate Athletic Association (NCAA) Division I athletes demonstrated that 165 (29%) felt there was nothing wrong with using painkillers on the day of competition to cope with injury-related pain .
This article reviews the evidence surrounding the use of pain medications in athletes and the ethical debates regarding pain management in athletes. Ethical considerations include the voluntary nature of sports, treating athletes under the legal age of consent, and blurring the lines between what is most important to a player: short-term pain relief for performance or longer-term consequences of potential increases in injury severity. Although this review is not intended to settle these ethical issues, the team physician must weigh the risks and benefits of treating pain in athletes and balance the ethical considerations.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
NSAIDs are a commonly used class of drugs available both OTC and by prescription. NSAIDs are taken for a myriad of reasons, including treatment of pain, soft tissue swelling, fever, and sprains/strains, especially overuse strains. Given the easy OTC access, many people assume that there is little risk involved in taking these medications. Although NSAIDs have shown promise in treating painful inflammatory conditions such as rheumatoid arthritis, beneficial effects of NSAIDs in common musculoskeletal injuries are not clearly established in the medical literature. The decision to use these medications should consider several issues regarding safe and appropriate use. A concise and thorough review of the numerous studies involving NSAIDs was published in the BMJ's Clinical Evidence [2••].
Mechanism of action is the first aspect of NSAIDs that should be considered prior to prescribing. Traditional NSAIDs act in the body by nonselectively blocking cyclooxygenase (COX). COX's primary mechanism of action is to catalyze the transformation of arachidonic acids to prostaglandins. There are two main forms, COX-1 and COX-2, each producing different prostaglandins. COX-1 is present at all times in the human body and is responsible for basal functions such as protection of the gastric mucosa and platelet aggregation. COX-2 is an inducible enzyme created and up-regulated during times of injury.
Traditional NSAIDs inhibit both COX-1 and COX-2, leading to decreased inflammatory response, but the decrease in gastric mucosa protection also increases the risk of gastrointestinal irritation. COX-2–specific inhibitors were developed with the goal of suppressing the inflammation produced by up-regulation of COX-2 after injury while sparing the gastrointestinal tract. This is accomplished by not inhibiting prostaglandin secretion in the gastric wall mucosa. Unfortunately, that concept did not take into account the effects on prostacyclin produced in vascular endothelial cells. Without prostacyclin, thromboxane A2 (mediated by COX-1) is unopposed, creating a potential shift in the tissue balance away from prostacyclin's vasodilatory and antiplatelet effects and toward more deleterious vasoconstriction and platelet aggregation. This shift's end result theoretically promotes thrombosis; more than one COX-2 inhibitor has been removed from the market following an increase in cardiovascular events.
Before prescribing NSAIDs, it also is important to consider the natural healing process when no extrinsic factors are in play and how these medicines may interfere with that process. Injuries that trigger the inflammatory cascade allow for signaling to increase blood flow to the area and recruitment of inflammatory cells that are an important part of the healing response. Although this process occurs in a predictable fashion, certain stages require a brisk inflammatory response to be successful and to prepare the injured tissue for the final reconstruction of elements to produce complete healing. NSAID inhibition of the early inflammatory response theoretically could impact or alter natural healing.
NSAIDs have been widely used to treat acute ankle sprains. It has long been believed that NSAIDs would decrease pain and swelling after an ankle sprain, which would potentially allow for earlier return to activity. This was supported by the results of the Kapooka Ankle Sprain Study, but the results also included some unexpected downsides of NSAID use for ankle sprains . In the study, 364 Australian Army recruits were randomized to placebo or piroxicam after an acute ankle sprain suffered during training. The recruits treated with piroxicam had less pain, returned to training more rapidly, and had increased exercise endurance upon resumption of training compared with those on placebo.
On the negative side, the piroxicam group had significantly more nausea than the placebo group (6.8% vs 0.3%). The authors also noted “interestingly” that the group treated with piroxicam had more instability and decreased range of motion (ROM) compared with the placebo group at the study's end. Piroxicam use decreased pain and hastened return to activity, but it is debatable whether the more rapid return was due to quicker healing of the injury (unlikely given the instability and lesser ROM compared with the placebo group) or simply blunting pain prior to the normal healing process' completion.
When cortical bone is injured, prostaglandins such as PGE2 have a pivotal role in response to the insult. PGE2 acts to replicate and differentiate osteoblast and osteoclast precursors, which lead to increased bone resorption and new bone formation . NSAID inhibition of prostaglandins may have detrimental effects on bone healing immediately after injury.
Indomethacin has been used to reduce heterotopic ossification (HO) risk following surgery for an acetabular fracture. In this role, it has been shown to decrease HO. However, a study of prophylactic use of indomethacin to prevent HO following acetabular surgery found a higher incidence (29% vs 7%) of nonunion of associated long bone fractures versus both placebo and radiation therapy to prevent HO . The study concluded that indomethacin for HO prophylaxis should be used with caution or substituted with other means if there are associated long bone fractures. The authors also recommended against the use of NSAIDs for analgesic or anti-inflammatory purposes following a fracture.
In 2005, Koester and Spindler  studied the effects of NSAID use on bone healing in spinal fusion literature and in fracture care. The review demonstrated a decrease in spinal fusion rates when ketorolac (COX-1) was used post-operatively, but not with celecoxib (COX-2). The only prospective study that looked at fracture healing showed no difference in rates of nonunion in postmenopausal women with distal radius fractures. Some retrospective studies that suggested NSAIDs decreased fracture healing were criticized because they relied on patient recall of NSAID use in the months following a fracture, an investigation design that would be hard-pressed to clearly demonstrate a cause-and-effect relationship.
In their conclusion, Koester and Spindler  state that the reviewed population is not at all similar to an athletic population with acute pain, as most studies were in older patients with multiple comorbidities that could affect bone healing. They further state that given the available literature, NSAID use at proper dosages is not contraindicated in fracture care. The risk–benefit ratio of decreasing acute pain with a theoretical risk of longer healing time must be considered and discussed with the athlete.
Acetaminophen is a widely available OTC medication that is effective as both an antipyretic and an analgesic. The low cost and long history of efficacious use make it an appealing option for treating pain. In healthy, adult-sized athletes who adhere to the recommended dosing schedule of no more than 4000 mg per 24 hours, the medication is safe with a low incidence of adverse effects. Caution must be taken in athletes who consume alcohol, have underlying liver disease, or take other medications with significant hepatotoxicity. Overdoses can be fatal unless promptly recognized and treated.
Acetaminophen often is overlooked in favor of NSAIDs due to concern of pain relief efficacy. Woo et al.  carried out a prospective, double-blind, randomized controlled trial comparing acetaminophen alone with diclofenac, indomethacin, or diclofenac combined with acetaminophen for treating blunt limb injury pain presenting to an emergency department. The study used 1000 mg four times daily against the usual doses of the NSAIDs. At study completion, the combination acetaminophen–diclofenac, acetaminophen alone, indomethacin alone, and diclofenac alone all provided similar analgesia with a similar and low side effect profile. Failure of adequate analgesia with acetaminophen may be due to medication underdosing.
Acetaminophen's mechanism of action has yet to be completely established. There are published findings of an additional COX enzyme, COX-3, found in the central nervous system that may be the site of action for acetaminophen and explain its ability to act as both an analgesic and antipyretic . Others believe that COX-3 might play a greater role in canines, but not humans, thereby questioning COX-3 as the target for acetaminophen . More research in this area is needed.
Sports medicine physicians often use injections for the targeted delivery of medications. Whether it is anesthetics, corticosteroids, NSAIDs, or other injectables, this treatment method is akin to a “smart bomb.” Injections avoid most of the systemic side effects and deliver higher doses to the intended tissue compared with the same medication administered orally. However, the provider must be aware that some agents may have some absorption beyond the target tissue, although the systemic levels typically are much lower than levels achieved via enteral administration.
Injecting requires skill, familiarity with anatomy, and knowledge of the medication's benefits and risks. Sterile preparation may minimize infection risk but often proves challenging in the training room. Injections pose a risk of bleeding and injury to adjacent structures. As with dispensing medications, informed consent must be obtained prior to administering injections. Most high school athletes are too young to legally provide consent; thus, parents must be consulted if injections are considered as a part of the pain management plan.
Injections often are viewed as more aggressive treatment typically reserved for higher-level athletes. Using injections to treat sports-related injury pain is not unheard of, yet the medical literature does not lend support to the practice. Orchard  published the results of a case series involving professional Australian football and rugby players treated with injection of local anesthetics (without corticosteroid) to facilitate quicker return to play. This was an important first step to try to adequately describe the benefits and risks associated with injections for sports injury.
Over the course of 6 years, in his role as team physician, Orchard  treated 2851 injuries in professional Australian football and rugby players. Of the 2851 injuries, 221 (8%) were treated with injection of the local anesthetic bupivacaine. These included injuries to the ribs, iliac crest (hematomas), acromioclavicular (AC) joint, fingers, thumb, ankles, metacarpals, sternum, and toes. A total of 86 (39%) of these injections were administered to treat acute injury with the game in progress, whereas the other treatments were administered for both acute and chronic pain prior to a game to allow the athlete to participate.
Complications were broken down into major or minor. Out of 221 injections, there were 17 complications (8%)—six (3%) were major and 11 (5%) minor. All six of the major complications did well with eventual return to play. Some of these injuries needed surgery to provide definitive treatment, but the author believed it was possible that some of those injuries would have needed surgery regardless of the injection to allow for return to play, and the injections allowed the athlete to continue playing until season's end.
Orchard  developed a classification system for injuries that could be treated with routine caution and those that could be treated with extreme caution and only if the rewards outweighed the risks. In the “routine caution” category were injuries to the AC joint, phalanges, metacarpals, ribs, sternum, and iliac crest, as well as chronic plantar fasciitis. The second category of higher-risk injuries included ankle sprains, tendon injuries, prepatellar and olecranon bursa swelling, and thumb and radiocarpal injuries.
This study was limited in that it was nonrandomized, uncontrolled, and of limited follow-up, as it represented a series of cases treated by one physician. Despite those limitations, it was an important first step in quantifying the risks and benefits of anesthetic injections for treating athletic injuries. Perhaps future studies could look at the long-term follow-up of these injuries and treatments.
It warrants mentioning that Orchard  only used anesthetics without corticosteroid in treating the players. Various corticosteroids often are used in combination with anesthetics. Steroids' role in these types of injections is controversial. Steroid injections can produce pain relief of much longer duration than anesthetic alone can produce in certain conditions. Such relief has even been demonstrated in conditions in which inflammation plays little role (such as chronic tendinopathy), which suggests the mechanism of action is beyond anti-inflammatory action alone. Although these injections yield less-than-ideal results for providing cure or extended pain relief in chronic tendinopathy, many physicians still use these treatments in noninflammatory processes.
Steroid injections also carry more risks than nonsteroid percutaneous injections. Adverse events include fat atrophy, skin lightening, blood sugar elevation (particularly in diabetics) , and a theoretical risk of suppression of immune response to an infection mistaken for inflammation.
Whereas teaching in medicine commonly discourages injection of corticosteroids directly into tendons and muscles, it has been done successfully in the highest level of athlete. Levine et al.  reported on their 13-year history of caring for a National Football League (NFL) team in which acute, severe hamstring strains were treated with intramuscular corticosteroids . After a retrospective review of the records for one NFL team, it was noted that 58 players suffered a severe hamstring injury with associated palpable defect in the muscle. These players were treated with corticosteroids and analgesics injected directly into the injury site. The injection was administered after the injured player identified the area of pain by pointing. The physician then prepped the area in sterile fashion and injected intramuscularly 3 mL of 1% lidocaine and 1 mL of dexamethasone (4 mg) via a 25-gauge needle. A compressive device was applied afterward, and the player held out of all activities for 48 hours. None of the players had any complications, and only nine (16% of the 58) missed any games as a result of treating the hamstring injury this way.
Concern of delayed healing or facilitating tendon rupture has prompted many practitioners to avoid injecting tendons directly, so the reporting of such treatments was a bold and significant contribution to the literature. However, it should be noted that the retrospective review had no control group or blinding to the procedure. Furthermore, the NFL athlete represents a unique patient population with different pressures and responsibilities than the average athlete; thus, generalization to all athletes might be unwise.
Other types of injections are sometimes used by sports medicine physicians, including prolotherapy (dextrose or other proinflammatory injections), autologous blood, or platelet-rich plasma (spun down from whole blood via centrifugation). These injections usually are meant to provoke an inflammatory response, not to suppress it. The prevailing theory behind such treatments is to trick the body into thinking a new injury has occurred by reinitiating inflammation to promote healing of ligament or tendon tissue that did not heal appropriately. The nature of these treatments requires influx of immune cells to try to repair damaged tissue, and the treatments require time to heal. Given the time needed to see an effect, they are not often used in the acute management of pain in sports, but more as an alternative treatment option for chronic injuries.
Athletes use many topical remedies. An extremely thorough and well-done review of the medical evidence of various transdermal treatments was published in this journal . The authors concluded that there is good evidence to use/recommend ice, electrical stimulation, iontophoresis, and several topical preparations for analgesic effect, although little evidence suggested a faster return to play with any modality. The review also highlighted lack of sufficient evidence to recommend laser, magnet, phonophoresis, or therapeutic ultrasound.
Topical medications, including NSAIDs, hold a lot of promise by delivering medicines known to be effective, only without the associated risks when administered orally. Topical NSAID preparations, some with good evidence to support their use, are not commercially available in the United States. These formulations can be made by a compounding pharmacy. A prospective, double-blind, randomized controlled trial of once-daily topical ketoprofen patch was performed in France  and found a statistically significant decrease in pain for the topical ketoprofen group versus the placebo group. Treatment with topical NSAIDs can keep plasma levels low (thereby limiting systemic adverse events) while allowing penetration into soft tissues of an injured extremity.
Some practitioners have used transdermal lidocaine patches to treat athletic injuries. Currently, the only US Food and Drug Administration–approved indication for Lidoderm (Endo Pharmaceuticals, Chadds Ford, PA), the only commercially available lidocaine patch, is for treating pain due to postherpetic neuralgia. Although it may play a role in treating musculoskeletal pain, the authors were unable to find any studies demonstrating efficacy of lidocaine patches for athletic injuries.
High-quality pain control and sports injury studies are lacking. Although there are some prospective, double-blind, randomized controlled trials, the sample sizes are often small, and the study designs flawed. As with many aspects of musculoskeletal medicine, there is no iron-clad, evidence-based medicine regarding pain. This requires the sports medicine physician to synthesize the available data and combine it with experience, anecdotal reports, and common sense. Therein lies the art of medicine.
It is common practice to use acetaminophen or NSAIDs for the initial treatment of injury and pain. When using NSAIDs, the aim should be to use the lowest effective dose for the shortest duration to avoid adverse events. More aggressive treatments, such as anesthetic injections, depend on the injury's location and severity and the level of competition. Certain injections, such as AC joint, can be administered with predictable results and low risk. Occasionally, more potent analgesics, such as tramadol or narcotics, will be needed, but it is best to only prescribe those medications after others have failed or for a short, initial course to bridge the initial healing phases. Other key aspects of NSAIDs in management of sports-related injuries can be found in a number of other important reviews [15,16••,17,18].
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance: •• Of major importance
1. Tricker R: Painkilling drugs in collegiate athletics: knowledge, attitudes, and use of student athletes.J Drug Educ
2.•• Gotzsche PC: Non-steroidal anti-inflammatory drugs.BMJ Clin Evid
Excellent and thorough review of the latest literature regarding NSAIDs (including COX-2 inhibitors), detailing head-to-head studies, critiquing meta-analyses, and explaining risks and benefits of use.
3. Slatyer MA, Hensley MJ, Lopert R: A randomized controlled trial of piroxicam in the management of acute ankle sprain in Australian regular army recruits.Am J Sports Med
4. Kawaguchi H, Pilbeam CC, Harrison JR, Raisz LG: The role of prostaglandins in the regulation of bone metabolism.Clin Orthop Relat Res
5. Burd TA, Hughes MS, Anglen JO: Heterotopic ossification prophylaxis with indomethacin increases the risk of long-bone nonunion.J Bone Joint Surg Br
6. Koester MC, Spindler KP: NSAIDs and fracture healing: what's the evidence?Curr Sports Med Rep
7. Woo WW, Man SY, Lam PK, Rainer TH: Randomized double-blind trial comparing oral paracetamol and oral nonsteroidal antiinflammatory drugs for treating pain after musculoskeletal injury.Ann Emerg Med
8. Chandrasekharan NV, Dai H, Roos KL, et al.: COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression.Proc Natl Acad Sci U S A
9. Kis B, Snipes JA, Busija DW: Acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts, fictions, and uncertainties.J Pharmacol Exp Ther
10. Orchard JW: Benefits and risks of using local anaesthetic for pain relief to allow early return to play in professional football.Br J Sports Med
11. Wang AA, Hutchinson DT: The effect of corticosteroid injection for trigger finger on blood glucose level in diabetic patients.J Hand Surg [Am]
12. Levine WN, Bergfeld JA, Tessendorf W, Moorman CT: Intramuscular corticosteroid injection for hamstring injuries: a 13-year experience in the National Football League.Am J Sports Med
13. Bolin DJ: Transdermal approaches to pain in sports injury management.Curr Sports Med Rep
14. Mazieres B, Rouanet S, Velicy J, et al.: Topical ketoprofen patch (100 mg) for the treatment of acute ankle sprain.Am J Sports Med
15. Lippi G, Franchini M, Guidi GC: Non-steroidal anti-inflammatory drugs in athletes.Br J Sports Med
16.•• Mehallo CJ, Drezner JA, Bytomski JR. Practical management: nonsteroidal antiinflammatory drug (NSAID) use in athletic injuries.Clin J Sport Med
Very thorough overview of the evidence on NSAIDs and athletic injuries. Unfortunately, it does not discuss other analgesics to be used instead if the main goal is analgesia.
17. Paoloni JA, Orchard JW: The use of therapeutic medications for soft-tissue injuries in sports medicine.Med J Aust
18. Stovitz SD, Johnson RJ: NSAIDs and musculoskeletal treatment. What is the clinical evidence?Phys Sportsmed
. Accessed September 10, 2007.