Analgesics in many different forms are available for pain relief. An analgesic is a drug or preparation that reduces or eliminates pain. Analgesics can be broken down into two basic categories: opioids and nonopioids. Opioid drugs were originally discovered as naturally occurring substances extracted from the opium poppy. The natural form is derived from the dried seeds of the poppy, which are processed to derive multiple active compounds. The opioids are well known for their ability to relieve moderate and severe pain symptoms. Drug manufacturers have developed semisynthetic and synthetic opioid derivatives that have effects similar to those of the naturally occurring form. Two of the best known compounds are morphine and codeine. Both morphine and codeine have similar chemical structures (Fig. 10–1) and both produce an analgesic effect in the body. With continued processing of the opium seeds, the drug heroin can be extracted. Thus it becomes apparent that this class of drugs is one in which physical dependence is a significant adverse effect.
Physical dependence signs and symptoms are typically demonstrated when a user stops taking the drug. An athlete who is physically dependent on an opioid will demonstrate withdrawal signs and symptoms such as irritability, sweating, insomnia, and tachycardia. An athlete who is psychologically dependent will exhibit behaviors that indicate he or she is craving or seeking the purchase of drugs. If the athlete is truly experiencing pain, the effect of addiction is diminished.
Implications for Activity
Athletes using analgesics have to be aware that, when they are using these drugs, they have a reduced perception of pain. If an athlete using analgesics gets injured, he or she may not be able to perceive the injury or convey the appropriate pain responses to the athletic trainer evaluating him or her. Athletes should not use analgesics to mask pain in order to continue participating.
Endogenous opioids such as endorphins and enkephalins circulate throughout the body on an "as-needed" basis. The endorphins are naturally occurring morphinelike substances and are thought to bind to receptor sites on the pain-mediating pathways. The enkephalins have a similar function to that of the endorphins; they bind to different receptor sites but provide the same type of pain mediation. These endogenous opioids are considered more potent than morphine. Endogenous opioids are available to the central nervous system (CNS) for analgesic purposes. However, these endogenous substances do not exist in the same concentrations as exogenous opioids.
Opioid receptors have been identified in the peripheral nerves. Circulating endogenous opioids can bind to these sites and decrease the excitability of the peripheral sensory neurons, thereby providing an analgesic effect.11 The endogenous opioids are thought to be more active in the peripheral tissues when one is dealing with an inflammatory process and analgesia is needed.10
Internet Resource Box
To learn more about pain in general, go to the American Association of Pain Management's Website, which contains a great deal of information and links:
The World Health Organization (WHO) has produced a treatment progression for physicians and others treating pain. The WHO outlined a three-step procedure (see Table 10–1) that health professionals can follow when addressing the problems associated with pain management. The WHO panel described pain in three categories: mild, moderate, and severe.
If the athlete is experiencing pain in the mild category, nonopioid medications such as acetaminophen, NSAIDs, or COX-2 inhibitors are recommended (see Chapter 3 for more details on these drugs). In the moderate pain category, if necessary, the physician may prescribe morphine or the related opioids such as hydrocodone and oxycodone. If the athlete is experiencing severe pain, the physician may choose methadone or a related opioid for pain control. The steps outlined in the WHO ladder (Fig. 10–2) give the medical provider good direction when helping an athlete to overcome pain for any situation. In some athletes there may be individual intolerances or contradictions to the use of NSAIDs or other drugs, which would indicate the use of an opioid for pain relief. Additionally, the athlete may need greater relief from pain, which may require an opioid drug. The physician should be the person who judges the severity of the pain that the athlete is experiencing and prescribes the proper analgesic for the level of pain. The specific drugs mentioned here will be discussed in more detail further on in this chapter.
Three-step pain management process (World Health Organization, Guidelines for Analgesic Drug Therapy, 2003, p. 25, with permission).
Opioids' Mechanism of Action
Opioid receptors were among the first receptors in the brain to be characterized for a specific activity. In addition to receptors in the CNS, there are opioid receptors in peripheral tissues. The opioid receptors are classified into three categories: mu (μ), kappa (κ), and delta (Δ). Theoretically, any of the opioids can attach to any of the receptors and act as an agonist or antagonist. Typically, there are specific drugs that bind to one or two of the three receptors and cause a change based on the drug-receptor combination. When the physician prescribes an opioid, he or she is usually prescribing a mu receptor agonist, which results in pain relief. Sometimes drug-related euphoria is an adverse effect experienced from the use of this type of drug.
Some drugs have an agonist effect on the mu receptor and an antagonist effect on the kappa receptor. Additionally, it should be noted here that the mu, kappa, and delta receptors have other functions in the body. Alteration of their functions can result in an adverse effect of the drug. For example, a mu receptor agonist can also be associated with respiratory depression, pupillary constriction, changes in self-image, and increased energy. These and other adverse effects will be discussed further on in this chapter.
Table 10-3Opioid Receptors and Physiological Responses ||Download (.pdf) Table 10-3 Opioid Receptors and Physiological Responses
|Opioid Receptor ||Related Response |
|Mu (μ) ||Analgesia, euphoria, respiratory depression |
|Kappa (κ) ||Spinal analgesia, general sedation |
|Delta (Δ) ||Euphoria, general sedation |
Opioid drugs act on the body by producing a decrease in neurotransmitter activity at both the presynaptic and postsynaptic sites, which alters the nocioceptive transmissions to the brain. The excitability of the neuron is altered as the opioid attaches to the potassium, calcium, or cyclic adenosine monophosphate (cAMP) activity at the synaptic site, resulting in a decrease in potassium or calcium conductance or cAMP second-messenger synthesis. These changes in activity at the synapse will result in changes at other sites along the neural pathway. In the case of the spinal cord, the opioid activity will result in an inhibition of the release of substance P (neurotransmitter) at the substantia gelatinosa. This decrease in substance P release produces an analgesic effect.6.
Internet Resource Box
The Canadian Pain Society Position Statement on Opioid Use can be found at:
Opioid use must be prescribed and monitored by the physician. This class of drugs is tightly controlled in the United States, mainly because of the potential for addiction. When used properly, these drugs are generally safe and effective. Children and adolescents react to opioids in much the same way as adults. These drugs can be prescribed for both acute and long-term pain syndromes. A common use of opioids is to treat chronic pain in cancer patients. Their use for treatment of chronic noncancer pain was not common in the United States before the early 1980s. In athletics, the physician generally prescribes these drugs for acute pain, such as pain resulting from surgery or severe trauma.
Physicians use a set treatment plan when prescribing an opioid analgesic. This plan will most likely have the athlete taking normal dosages of the prescription drug initially, followed by small increases in the dose until the athlete begins to experience relief from the pain. The dosage will then be leveled off and the athlete will be slowly withdrawn from the drug. In most cases this takes less than a week. By then, the athlete should have suitable pain relief and can begin a rehabilitation program.
According to Scott-Levin, a pharmacology consulting firm in Newtown, Pennsylvania, the single most prescribed drug in the year 2000 was hydrocodone with acetaminophen (APAP). Scott-Levin estimates that in more than 2.04 billion prescriptions for this drug alone were written in the year 2000. Table 10–4 outlines some of the more commonly prescribed oral opioid analgesics with which athletic trainers should be familiar in order to talk to athletes about their time of onset and duration of action. Hydrocodone (Vicodin, Lortab) is a semisynthetic narcotic analgesic that is combined with acetaminophen in some preparations. It also has an antitussive action and is used in several cough-suppressant formulations. However, this drug is more commonly prescribed for pain.
Table 10-4Oral Opioid Analgesics
Oxycodone (prescribed under brand names including Oxy-Contin, Percocet, Percodan, Oxycodone, Roxicodone, Endocet, Roxicet, Roxilox, Tylox, Endodan, and Roxiprin) can be prepared in combination with acetaminophen or other similar analgesics. It is an opioid analgesic and, like other controlled drugs, must be prescribed by a physician. There is a high risk that an athlete will develop a tolerance if he or she uses this drug over a long period of time. These drugs can be abused by athletes and others, and the use of such drugs must be monitored by the athletic trainer. As with other opioids, this drug is contraindicated in conjunction with other CNS depressants such as alcohol.
Codeine is another mild to moderate agonist that can be prescribed by a physician or dentist to alleviate pain. It is also used as an antitussive for those experiencing severe coughing from the common cold or other upper respiratory tract infections. Codeine can also be habit forming, and the athletic trainer should be aware of any athlete who takes codeine for long periods of time. The most common complaint with the use of codeine is constipation.
Adverse Effects of Exogenous Opioids
As mentioned, this class of drugs can be addictive, which is an important concept for the athletic trainer to keep in mind. It is suggested that persons who have other addictive behaviors should be closely monitored when using these drugs. The ability of these drugs to become addictive suggests that the athletic trainer should monitor the athlete during the use of these drugs and discuss their use with the physician.
The opioids in general can cause sedation, nausea, vomiting, and constipation. The use of opioids with alcohol or other CNS depressants has an additive effect. Taking hydrocodone or other opioid drugs in combination with alcohol or other CNS depressants can be lethal. This is an important point to stress to the high school or college athlete who may be experimenting with or using alcohol regularly. Respiratory depression when taking opioids, and other drug interactions with alcohol or CNS depressants, all of which may cause other health problems or even death, must be explained to the athlete.
As mentioned previously, the physician will prescribe only a limited amount of an opioid drug after surgery to help reduce the associated pain. In most situations, an athlete will be using the drug for less than 10 days, so the opportunity for developing tolerance or dependence is decreased. If the athletic trainer notices that an athlete is taking an opioid for longer periods of time, it may be that the athlete is obtaining extra medication from multiple sources. Suspicion of inappropriate use should be reported to the physician immediately. In a published article by Jonasson et al.,5 22 percent of the orthopedic and chronic pain population they interviewed was considered to have an analgesic use disorder. An even higher percentage, 33 percent, met the criteria for having a substance use disorder.
It is recommended that physicians be aware of whether a patient has addictive behaviors before they prescribe an opioid for analgesia. Coambs et al3 (1996) developed the Screening Instrument for Substance Abuse Potential (SISAP) (Table 10–5). The athletic trainer can implement it and convey the information derived from it to the team physician.
Table 10-5Screening Questions for Potential Opioid Abuse ||Download (.pdf) Table 10-5 Screening Questions for Potential Opioid Abuse
|Question ||Use Caution When: |
|How many alcoholic drinks do you have on a typical day? ||Men have >4 drinks/day or 16 drinks/week |
| In a typical week? ||Women have >3 drinks/day or 12/week |
|Have you used marijuana or hashish in the past year? ||Use extreme caution in prescribing opioid therapy to a patient who uses cannabis. Use for recreational purposes is of concern in this case. |
|Have you ever smoked cigarettes? ||This indicates addictive behavior. |
|What is your age? ||A person under the age of 40 who smokes should be approached with concern. |
It should also be remembered that many prescription opioid pain relievers are combined with acetaminophen or aspirin. The maximum amount of acetaminophen that an athlete with a healthy liver can safely take is 4000 mg per day. If the athlete uses alcohol or has impaired liver function, the maximum daily amount is 2000 mg. People with liver failure should not take acetaminophen. Acetaminophen and aspirin are included in many OTC products also. The athlete should carefully read the label of each OTC drug he or she is considering using to determine all of the ingredients it contains. The athletic trainer should check with the physician or pharmacist to determine if any extra acetaminophen or aspirin can be taken along with the prescription medication.
As mentioned previously, the opioids are known to induce a tolerance effect in some individuals. Tolerance in this situation means that an increasing amount of the drug is required to maintain the same level of analgesia. Tolerance development can be affected by dose, frequency of administration, and regularity of dosing. In the case of the opioids, an increase in tolerance alone does not indicate that a person is addicted to the drug, but an increased tolerance can be a part of the addiction process. It has been shown that 10 to 20 times the initial dose may be needed to control pain in some drug-tolerant individuals. Even though a tolerance effect can start in the first days of taking an opioid, it is not common, and the typical athlete's regimen of taking the drug for less than a week seldom initiates a tolerance response. Tolerance is an important concept for the athletic trainer to understand because tolerance development is normal and expected when opioids are used for long periods of time. The physician can increase the opioid dosage over time. Athletes (and all patients) need to be reassured that this increased dosage does not mean that they are becoming addicted to the medication. When opioids are prescribed for a pain-related condition, addiction does not commonly occur.
Occasionally, opioid drugs can cause respiratory depression and orthostatic hypotension, even at normal doses. The key physiological signs to look for in an athlete possibly overusing these drugs are reduction of respiratory rate and depth, somnolence, euphoria, sedation, slurred speech, and judgment difficulties. If these adverse effects are noted, the dose may be too high or the patient may be overdosing himself or herself. These drugs have an additive effect when combined with other CNS depressants. Ingesting opioids in combination with alcohol or other CNS depressants can result in severe side effects. Opioids taken in conjunction with other CNS depressants have been identified as causes of accidental and self-inflicted fatalities.
As mentioned previously, opioids can create sedation, drowsiness, and an overall mental slowdown. It is wise to schedule rehabilitation or other activities that require mental acuity at times when the drug is at a period of reduced activity. Another possible adverse effect of the opioids is a perception of euphoria, mood changes, or relief from anxiety, which varies from athlete to athlete. This is an adverse effect that needs close monitoring by the physician with help from the athletic trainer.
Because the opioids have an antiperistaltic action, constipation can be an unwanted adversee effect. The physician needs to be aware of any constipation that the athlete may be experiencing. Treatment regimens are available for opioid-associated constipation and should be followed when the athlete is experiencing this adverse effect. Nausea or vomiting can be a problem at lower doses, although at higher doses the vomiting response can be depressed.9 Taking the medication with food often helps with opioid-associated nausea.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used widely for management of pain as well as inflammation. Because of the many types and wide uses of these drugs, we have dedicated a chapter to the anti-inflammatory drugs. Please see Chapter 3 for more information regarding NSAIDs.
One of the most popular nonopioid prescription medications is propoxyphene (Darvon, Darvocet, Darvon-N), which is a mild to moderate agonist. Propoxyphene has a high propensity for addiction among users and has a significant toxic effect when used with other CNS depressants. The toxic effect is mainly depression of the CNS, which results in respiratory difficulty and/or failure. This drug is now prescribed for pain control only on an occasional basis. Propoxyphene ranks second to barbiturates in causing prescription drug fatalities.
Another OTC preparation that is being used more and more is capsaicin, also marketed by the trade name Zostrix. Capsaicin is derived from the seeds of hot chili (capsicum) peppers such as habañero, Jamaican hot, cayenne, and jalapeño. Researchers now have determined that capsaicin limits the activity of substance P in transmitting pain messages from the extremities to the brain.2 Capsaicin is generally marketed for arthritic individuals or persons with some type of atypical pain such as shingles or other neuropathic pain. However, athletes are discovering the use of this product, which is topically applied as a cream. The OTC preparations have a smaller percentage (0.025–0.075%) of the active ingredient, but there are products being tested that have 5 to 10 percent capsaicin. The higher concentrations appear to provide some analgesia and pain relief.8
The athletic trainer should be fully aware of whether the athlete is using any OTC preparation before participation in activity. An athlete should not use an analgesic to mask any pain. When an athlete is not physically ready for practice or competition, he or she should not use an analgesic in an attempt to overcome any warning signals the body may be sending to avoid tissue damage.
Athletes' Understanding of Analgesic Drugs
It is interesting to review the comments of collegiate athletes questioned about "painkilling drugs" and the use of those drugs. In a study reported by Tricker,12 over 2/3 of 563 athletes surveyed responded that they were aware that painkilling drugs were potentially addictive. When asked for a self-report on the use of such drugs, more than half of the athletes indicated that they used painkilling drugs when injured, sick, or sore after workouts, regularly throughout the season. The athletes in this study generally considered themselves to be overusers of painkilling drugs. Additionally, they reported that they did not obtain the painkilling drugs from physicians, but rather from sources such as teammates, friends, and parents. The actual types of painkilling drugs used were not reported in this study, but it gives a sense of how many athletes are using drugs that produce analgesia.
The physician and athletic trainer should monitor any OTC medications taken by the athlete that produce analgesia because a reduction in pain may allow further tissue damage if an athlete participates without regard for the internal warning signals his or her body produces. Additionally, the athlete should report any use of herbal preparations because of the possibility of adverse interactions between many analgesics and herbal medications. Some herbal medications (such as echinacea and kava-kava), when used in conjunction with OTC or prescription analgesics (such as acetaminophen and opioids, respectively), can lead to hepatotoxicity and nephrotoxicity, among other problems. The effectiveness of some analgesics can be inhibited by herbal supplements. A good review of the potential for adverse interactions between herbal medications and analgesic drugs is available in the recent article by Abebe.1
The athletic trainer should observe athletes whom they suspect of overusing analgesics for indications of euphoria, judgment difficulties, and excessive sedation or sleepiness. The athlete might also suffer from respiratory rate reduction. It is not uncommon for an abuser of analgesics to attempt to obtain additional prescriptions for the medication from multiple providers. This allows the abuser to take more of the drug, which keeps him or her in an altered state more often.