Sometimes treating the underlying condition doesn't immediately relieve pain even though the ideal treatment for any pain is to remove the cause, thus diagnosis should always precede treatment planning. Furthermore, some conditions are so painful that rapid and effective analgesia is essential (for example, the postoperative state, burns, trauma, cancer, sickle cell crisis). Analgesic medications are a first line of treatment in these cases, and all practitioners should be familiar with their use.
Aspirin, Acetaminophen, and Nonsteroidal Anti-Inflammatory Agents (NSAIDS) are drugs that considered together because they are used for similar problems and may have a similar mechanism of action . All these compounds inhibit cyclooxygenase (COX), and, except for acetaminophen, all have anti-inflammatory actions, especially at higher dosages. They are particularly effective for mild to moderate headache and for pain of musculoskeletal origin. Since they are effective for these common types of pain and are available without prescription, COX inhibitors are by far the most commonly used analgesics. They are absorbed well from the gastrointestinal tract and, with occasional use, side effects are minimal. With chronic use, gastric irritation is a common side effect of aspirin and NSAIDs and is the problem that most frequently limits the dose that can be given. Gastric irritation is most severe with aspirin, which may cause erosion of the gastric mucosa, and because aspirin irreversibly acetylates platelets and thereby interferes with coagulation of the blood, gastrointestinal bleeding is a risk. The NSAIDs are less prob lematic, but their risk in this regard is still significant. In addition to their well known gastrointestinal toxicity, nephrotoxicity is a significant problem for patients using NSAIDs on a chronic basis, and patients at risk for renal insufficiency should be monitored closely. NSAIDs also cause an increase in blood pressure in a significant number of individuals.
Treatment with NSAIDs in long-term therapy requires regular blood pressure monitoring and treatment if necessary. Although toxic to the liver when taken in a high dose, acetaminophen rarely produces gastric irritation and does not interfere with platelet function. The introduction of a parenteral form of NSAID, ketorolac, extends the usefulness of this class of compounds in the management of acute severe pain. Ketorolac is sufficiently potent and rapid in onset to supplant opioids for many patients with acute severe headache and musculoskeletal pain.
There are two major classes of COX: COX-1 is constitutively expressed and COX-2 is induced in the inflammatory state. COX-2-selective drugs have moderate analgesic potency and produce less gastric irritation than the nonselective COX inhibitors. It is not yet clear whether the use of COX-2 selective drugs is associated with a lower risk of nephrotoxicity compared to nonselective NSAIDs. On the other hand, COX-2-selective drugs offer a significant benefit in the management of acute postoperative pain because they do not affect blood coagulation. This is a situation in which the nonselective COX inhibitors would be contraindicated because they impair platelet-mediated blood clotting and are thus associated with increased bleeding at the operative site. A corollary of this is that COX-2 drugs do not provide the same degree of protection from thromboembolic cardiovascular adverse events such as myocardial infarction. In fact, in patients treated for arthritis, those treated with naproxen had significantly fewer adverse thromboembolic events than those treated with rofecoxib, a selective COX-2 inhibitor.
Opioid Analgesics Opioids are the most potent pain-relieving drugs currently available. Furthermore, of all analgesics, they have the broadest range of efficacy, providing the most reliable and effective method for rapid pain relief. Although side effects are common, they are usually not serious except for respiratory depression and can be reversed rapidly with the narcotic antagonist naloxone. The physician should not hesitate to use opioid analgesics in patients with acute severe pain. Table 11-1 lists the most commonly used opioid analgesics. Opioids produce analgesia by actions in the central nervous system. They activate pain-inhibitory neurons and directly inhibit pain-transmission neurons. Most of the commercially available opioid analgesics act at the same opioid receptor (mu receptor), differing mainly in potency, speed of onset, duration of action, and optimal route of administration. Although the dose-related side effects (sedation, respiratory depression, pruritus, constipation) are similar among the different opioids, some side effects are due to accumulation of nonopioid metabolites that are unique to individual drugs. One striking example of this is normeperidine, a metabolite of meperidine. Normeperidine produces hyperexcitability and seizures that are not reversible with naloxone. Normeperidine accumulation is increased in patients with renal failure. The most rapid relief with opioids is obtained by intravenous administration; relief with oral administration is significantly slower.
Common acute side effects include nausea, vomiting, and sedation. The most serious side effect is respiratory depression. Patients with any form of respiratory compromise must be kept under close observation following opioid administration; an oxygen saturation monitor may be useful. The opioid antagonist, naloxone, should be readily available. Opioid effects are dose-related, and there is great variability among patients in the doses that relieve pain and produce side effects.
Because of this, initiation of therapy requires titration to optimal dose and interval. The most important principle is to provide adequate pain relief. This requires determining whether the drug has adequately relieved the pain and the duration of the relief. The most common error made by physicians in managing severe pain with opioids is to prescribe an inadequate dose. Since many patients are reluctant to complain, this practice leads to needless suffering. In the absence of sedation at the expected time of peak effect, a physician should not hesitate to repeat the initial dose to achieve satisfactory pain relief. An innovative approach to the problem of achieving adequate pain relief is the use of patient-controlled analgesia (PCA). PCA requires a device that delivers a baseline continuous dose of an opioid drug, and preprogrammed additional doses whenever the patient pushes a button. The device can be programmed to limit the total hourly dose so that overdosing is impossible. The patient can then titrate the dose to the optimal level. This approach is used most extensively for the management of postoperative pain, but there is no reason why it should not be used for any hospitalized patient with persistent severe pain. PCA is also used for short-term home care of patients with intractable pain, such as is caused by metastatic cancer. Many physicians, nurses, and patients have a certain trepidation about using opioids that is based on an exaggerated fear of addiction. In fact, there is a vanishingly small chance of patients becoming addicted to narcotics as a result of their appropriate medical use.
The availability of new routes of administration has extended the usefulness of opioid analgesics. Most important is the availability of spinal administration. Opioids can be infused through a spinal catheter placed either intrathecally or epidurally. By applying opioids directly to the spinal cord, regional analgesia can be obtained using a relatively low total dose. In this way, such side effects as sedation, nausea, and respiratory depression can be minimized. This approach has been used extensively in obstetric procedures and for lower-body postoperative pain. Opioids can also be given intranasally (butorphanol), rectally, and transdermally (fentanyl), thus avoiding the discomfort of frequent injections in patients who cannot be given oral medication. The fentanyl transdermal patch has the advantage of providing fairly steady plasma levels, which maximizes patient comfort.
OPIOID AND CYCLOOXYGENASE INHIBITOR COMBINATIONS
When used in combination, opioids and COX inhibitors have additive effects. Because a lower dose of each can be used to achieve the same degree of pain relief and their side effects are nonadditive, such combinations can be used to lower the severity of dose-related side effects. Fixed-ratio combinations of an opioid with acetaminophen carry a special risk. Dose escalation as a result of increased severity of pain or decreased opioid effect as a result of tolerance may lead to levels of acetaminophen that are toxic to the liver.
CHRONIC PAIN
Managing patients with chronic pain is intellectually and emotionally challenging. The patient’s problem is often difficult to diagnose; such patients are demanding of the physician’s time and often appear emotionally distraught. The traditional medical approach of seeking an obscure organic pathology is usually unhelpful. On the other hand, psychological evaluation and behaviorally based treatment paradigms are frequently helpful, particularly in the setting of a multidisciplinary pain-management center.
There are several factors that can cause, perpetuate, or exacerbate chronic pain. First, of course, the patient may simply have a disease that is characteristically painful for which there is presently no cure. Arthritis, cancer, migraine headaches, fibromyalgia, and diabetic neuropathy are examples of this. Second, there may be secondary perpetuating factors that are initiated by disease and persist after that disease has resolved. Examples include damaged sensory nerves, sympathetic efferent activity, and painful reflex muscle contraction. Finally, a variety of psychological conditions can exacerbate or even cause pain.
There are certain areas to which special attention should be paid in the medical history. Because depression is the most common emotional disturbance in patients with chronic pain, patients should be questioned about their mood, appetite, sleep patterns, and daily activity. A simple standardized questionnaire, such as the Beck Depression Inventory, can be a useful screening device. It is important to remember that major depression is a common, treatable, and potentially fatal illness.
Other clues that a significant emotional disturbance is contributing to a patient’s chronic pain complaint include: pain that occurs in multiple unrelated sites; a pattern of recurrent, but separate, pain problems beginning in childhood or adolescence; pain beginning at a time of emotional trauma, such as the loss of a parent or spouse; a history of physical or sexual abuse; and past or present substance abuse. On examination, special attention should be paid to whether the patient guards the painful area and whether certain movements or postures are avoided because of pain. Discovering a mechanical component to the pain can be useful both diagnostically and therapeutically. Painful areas should be examined for deep tenderness, noting whether this is localized to muscle, ligamentous structures, or joints. Chronic myofascial pain is very common, and in these patients deep palpation may reveal highly localized trigger points that are firm bands or knots in muscle. Relief of the pain following injection of local anesthetic into these trigger points supports the diagnosis. A neuropathic component to the pain is indicated by evidence of nerve damage, such as sensory impairment, exquisitely sensitive skin, weakness and muscle atrophy, or loss of deep tendon reflexes. Evidence suggesting sympathetic nervous system involvement includes the presence of diffuse swelling, changes in skin color and temperature, and hypersensitive skin and joint tenderness compared with the normal side. Relief of the pain with a sympathetic block is diagnostic. A guiding principle in evaluating patients with chronic pain is to assess both emotional and organic factors before initiating therapy. Addressing these issues together, rather than waiting to address emotional issues after organic causes of pain have been ruled out, improves compliance in part because it assures patients that a psychological evaluation does not mean that the physician is questioning the validity of their complaint. Even when an organic cause for a patient’s pain can be found, it is still wise to look for other factors. For example, a cancer patient with painful bony metastases may have additional pain due to nerve damage and may also be depressed. Optimal therapy requires that each of these factors be looked for and treated.
TREATMENT of CHRONIC PAIN
Once the evaluation process has been completed and the likely causative and exacerbating factors identified, an explicit treatment plan should be developed. An important part of this process is to identify specific and realistic functional goals for therapy, such as getting a good night’s sleep, being able to go shopping, or returning to work. A multidisciplinary approach that utilizes medications, counseling, physical therapy, nerve blocks, and even surgery may be required to improve the patient’s quality of life. There are also some newer, relatively invasive procedures that can be helpful for some patients with intractable pain. These procedures include implanting intraspinal cannulae to deliver morphine or intraspinal electrodes for spinal stimulation. There are no set criteria for predicting which patients will respond to these procedures. They are generally reserved for patients who have not responded to conventional pharmacologic approaches. Referral to a multidisciplinary pain clinic for a full evaluation should precede any of these procedures. Such referrals are clearly not necessary for all chronic pain patients. For some, pharmacologic management alone can often provide adequate relief.
ANTIDEPRESSANT MEDICATIONS
The tricyclic antidepressants (TCAs) are extremely useful for the management of patients with chronic pain. Although developed for the treatment of depression, the tricyclics have a spectrum of dose-related biologic activities that include the production of analgesia in a variety of clinical conditions. Although the mechanism is unknown, the analgesic effect of TCAs has a more rapid onset and occurs at a lower dose than is typically required for the treatment of depression. Furthermore, patients with chronic pain who are not depressed obtain pain relief with antidepressants. There is evidence that tricyclic drugs potentiate opioid analgesia, so they are useful adjuncts for the treatment of severe persistent pain such as occurs with malignant tumors. TCAs are of particular value in the management of neuropathic pain such as occurs in diabetic neuropathy and postherpetic neuralgia, for which there are few other therapeutic options. The TCAs that have been shown to relieve pain have significant side effects . Some of these side effects, such as orthostatic hypotension, cardiac conduction delay, memory impairment, constipation, and urinary retention, are particularly problematic in elderly patients, and several are additive to the side effects of opioid analgesics.
The serotonin-selective reuptake inhibitors such as fluoxetine (Prozac) have fewer and less serious side effects than TCAs, but they are much less effective for relieving pain. It is of interest that venlafaxine (Effexor), a nontricyclic antidepressant that blocks both serotonin and norepinephrine reuptake, appears to retain most of the pain-relieving effect of TCAs with a side-effect profile more like that of the serotonin-selective reuptake inhibitors. The drug may be particularly useful in patients who cannot tolerate the side effects of tricyclics.
ANTICONVULSANTS AND ANTIARRHYTHMICS
These drugs are useful primarily for patients with neuropathic pain. Phenytoin (Dilantin) and carbamazepine (Tegretol) were first shown to relieve the pain of trigeminal neuralgia. This pain has a characteristic brief, shooting, electric shock–like quality. In fact, anticonvulsants seem to be helpful largely for pains that have such a lancinating quality. A newgeneration anticonvulsant, gabapentin (Neurontin), is effective for a broad range of neuropathic pains.
Antiarrhythmic drugs such as low-dose lidocaine and mexiletine (Mexitil) can also be effective for neuropathic pain. These drugs block the spontaneous activity of damaged primary afferent nociceptors.
CHRONIC OPIOID MEDICATION
The long-term use of opioids is accepted for patients with pain due to malignant disease. Although opioid use for chronic pain of nonmalignant origin is controversial, it is clear that for many such patients opioid analgesics are the best available option. This is understandable since opioids are the most potent and have the broadest range of efficacy of any analgesic medications.
Although addiction is rare in patients who first use opioids for pain relief, some degree of tolerance and physical dependence are likely with long-term use. Therefore, before embarking on opioid therapy, other options should be explored, and the limitations and risks of opioids should be explained to the patient. It is also important to point out that some opioid analgesic medications have mixed agonist-antagonist properties (e.g., pentazocine and butorphanol). From a practical standpoint, this means that they may worsen pain by inducing an abstinence syndrome in patients who are physically dependent on other opioid analgesics.
With long-term outpatient use of orally administered opioids, it is desirable to use long-acting compounds such as levorphanol, methadone, or sustained-release morphine. Transdermal fentanyl is another excellent option. The pharmacokinetic profile of these drug preparations enables prolonged pain relief, minimizes side effects such as sedation that are associated with high peak plasma levels, and reduces the likelihood of rebound pain associated with a rapid fall in plasma opioid concentration. Constipation is a virtually universal side effect of opioid use and should be treated expectantly. It is worth emphasizing that many patients, especially those with chronic pain, seek medical attention primarily because they are suffering and because only physicians can provide the medications required for their relief. A primary responsibility of all physicians is to minimize the physical and emotional discomfort of their patients. Familiarity with pain mechanisms and analgesic medications is an important step toward accomplishing this aim.
Related article : Understanding Pain
Aspirin, Acetaminophen, and Nonsteroidal Anti-Inflammatory Agents (NSAIDS) are drugs that considered together because they are used for similar problems and may have a similar mechanism of action . All these compounds inhibit cyclooxygenase (COX), and, except for acetaminophen, all have anti-inflammatory actions, especially at higher dosages. They are particularly effective for mild to moderate headache and for pain of musculoskeletal origin. Since they are effective for these common types of pain and are available without prescription, COX inhibitors are by far the most commonly used analgesics. They are absorbed well from the gastrointestinal tract and, with occasional use, side effects are minimal. With chronic use, gastric irritation is a common side effect of aspirin and NSAIDs and is the problem that most frequently limits the dose that can be given. Gastric irritation is most severe with aspirin, which may cause erosion of the gastric mucosa, and because aspirin irreversibly acetylates platelets and thereby interferes with coagulation of the blood, gastrointestinal bleeding is a risk. The NSAIDs are less prob lematic, but their risk in this regard is still significant. In addition to their well known gastrointestinal toxicity, nephrotoxicity is a significant problem for patients using NSAIDs on a chronic basis, and patients at risk for renal insufficiency should be monitored closely. NSAIDs also cause an increase in blood pressure in a significant number of individuals.
Treatment with NSAIDs in long-term therapy requires regular blood pressure monitoring and treatment if necessary. Although toxic to the liver when taken in a high dose, acetaminophen rarely produces gastric irritation and does not interfere with platelet function. The introduction of a parenteral form of NSAID, ketorolac, extends the usefulness of this class of compounds in the management of acute severe pain. Ketorolac is sufficiently potent and rapid in onset to supplant opioids for many patients with acute severe headache and musculoskeletal pain.
There are two major classes of COX: COX-1 is constitutively expressed and COX-2 is induced in the inflammatory state. COX-2-selective drugs have moderate analgesic potency and produce less gastric irritation than the nonselective COX inhibitors. It is not yet clear whether the use of COX-2 selective drugs is associated with a lower risk of nephrotoxicity compared to nonselective NSAIDs. On the other hand, COX-2-selective drugs offer a significant benefit in the management of acute postoperative pain because they do not affect blood coagulation. This is a situation in which the nonselective COX inhibitors would be contraindicated because they impair platelet-mediated blood clotting and are thus associated with increased bleeding at the operative site. A corollary of this is that COX-2 drugs do not provide the same degree of protection from thromboembolic cardiovascular adverse events such as myocardial infarction. In fact, in patients treated for arthritis, those treated with naproxen had significantly fewer adverse thromboembolic events than those treated with rofecoxib, a selective COX-2 inhibitor.
Opioid Analgesics Opioids are the most potent pain-relieving drugs currently available. Furthermore, of all analgesics, they have the broadest range of efficacy, providing the most reliable and effective method for rapid pain relief. Although side effects are common, they are usually not serious except for respiratory depression and can be reversed rapidly with the narcotic antagonist naloxone. The physician should not hesitate to use opioid analgesics in patients with acute severe pain. Table 11-1 lists the most commonly used opioid analgesics. Opioids produce analgesia by actions in the central nervous system. They activate pain-inhibitory neurons and directly inhibit pain-transmission neurons. Most of the commercially available opioid analgesics act at the same opioid receptor (mu receptor), differing mainly in potency, speed of onset, duration of action, and optimal route of administration. Although the dose-related side effects (sedation, respiratory depression, pruritus, constipation) are similar among the different opioids, some side effects are due to accumulation of nonopioid metabolites that are unique to individual drugs. One striking example of this is normeperidine, a metabolite of meperidine. Normeperidine produces hyperexcitability and seizures that are not reversible with naloxone. Normeperidine accumulation is increased in patients with renal failure. The most rapid relief with opioids is obtained by intravenous administration; relief with oral administration is significantly slower.
Common acute side effects include nausea, vomiting, and sedation. The most serious side effect is respiratory depression. Patients with any form of respiratory compromise must be kept under close observation following opioid administration; an oxygen saturation monitor may be useful. The opioid antagonist, naloxone, should be readily available. Opioid effects are dose-related, and there is great variability among patients in the doses that relieve pain and produce side effects.
Because of this, initiation of therapy requires titration to optimal dose and interval. The most important principle is to provide adequate pain relief. This requires determining whether the drug has adequately relieved the pain and the duration of the relief. The most common error made by physicians in managing severe pain with opioids is to prescribe an inadequate dose. Since many patients are reluctant to complain, this practice leads to needless suffering. In the absence of sedation at the expected time of peak effect, a physician should not hesitate to repeat the initial dose to achieve satisfactory pain relief. An innovative approach to the problem of achieving adequate pain relief is the use of patient-controlled analgesia (PCA). PCA requires a device that delivers a baseline continuous dose of an opioid drug, and preprogrammed additional doses whenever the patient pushes a button. The device can be programmed to limit the total hourly dose so that overdosing is impossible. The patient can then titrate the dose to the optimal level. This approach is used most extensively for the management of postoperative pain, but there is no reason why it should not be used for any hospitalized patient with persistent severe pain. PCA is also used for short-term home care of patients with intractable pain, such as is caused by metastatic cancer. Many physicians, nurses, and patients have a certain trepidation about using opioids that is based on an exaggerated fear of addiction. In fact, there is a vanishingly small chance of patients becoming addicted to narcotics as a result of their appropriate medical use.
The availability of new routes of administration has extended the usefulness of opioid analgesics. Most important is the availability of spinal administration. Opioids can be infused through a spinal catheter placed either intrathecally or epidurally. By applying opioids directly to the spinal cord, regional analgesia can be obtained using a relatively low total dose. In this way, such side effects as sedation, nausea, and respiratory depression can be minimized. This approach has been used extensively in obstetric procedures and for lower-body postoperative pain. Opioids can also be given intranasally (butorphanol), rectally, and transdermally (fentanyl), thus avoiding the discomfort of frequent injections in patients who cannot be given oral medication. The fentanyl transdermal patch has the advantage of providing fairly steady plasma levels, which maximizes patient comfort.
OPIOID AND CYCLOOXYGENASE INHIBITOR COMBINATIONS
When used in combination, opioids and COX inhibitors have additive effects. Because a lower dose of each can be used to achieve the same degree of pain relief and their side effects are nonadditive, such combinations can be used to lower the severity of dose-related side effects. Fixed-ratio combinations of an opioid with acetaminophen carry a special risk. Dose escalation as a result of increased severity of pain or decreased opioid effect as a result of tolerance may lead to levels of acetaminophen that are toxic to the liver.
CHRONIC PAIN
Managing patients with chronic pain is intellectually and emotionally challenging. The patient’s problem is often difficult to diagnose; such patients are demanding of the physician’s time and often appear emotionally distraught. The traditional medical approach of seeking an obscure organic pathology is usually unhelpful. On the other hand, psychological evaluation and behaviorally based treatment paradigms are frequently helpful, particularly in the setting of a multidisciplinary pain-management center.
There are several factors that can cause, perpetuate, or exacerbate chronic pain. First, of course, the patient may simply have a disease that is characteristically painful for which there is presently no cure. Arthritis, cancer, migraine headaches, fibromyalgia, and diabetic neuropathy are examples of this. Second, there may be secondary perpetuating factors that are initiated by disease and persist after that disease has resolved. Examples include damaged sensory nerves, sympathetic efferent activity, and painful reflex muscle contraction. Finally, a variety of psychological conditions can exacerbate or even cause pain.
There are certain areas to which special attention should be paid in the medical history. Because depression is the most common emotional disturbance in patients with chronic pain, patients should be questioned about their mood, appetite, sleep patterns, and daily activity. A simple standardized questionnaire, such as the Beck Depression Inventory, can be a useful screening device. It is important to remember that major depression is a common, treatable, and potentially fatal illness.
Other clues that a significant emotional disturbance is contributing to a patient’s chronic pain complaint include: pain that occurs in multiple unrelated sites; a pattern of recurrent, but separate, pain problems beginning in childhood or adolescence; pain beginning at a time of emotional trauma, such as the loss of a parent or spouse; a history of physical or sexual abuse; and past or present substance abuse. On examination, special attention should be paid to whether the patient guards the painful area and whether certain movements or postures are avoided because of pain. Discovering a mechanical component to the pain can be useful both diagnostically and therapeutically. Painful areas should be examined for deep tenderness, noting whether this is localized to muscle, ligamentous structures, or joints. Chronic myofascial pain is very common, and in these patients deep palpation may reveal highly localized trigger points that are firm bands or knots in muscle. Relief of the pain following injection of local anesthetic into these trigger points supports the diagnosis. A neuropathic component to the pain is indicated by evidence of nerve damage, such as sensory impairment, exquisitely sensitive skin, weakness and muscle atrophy, or loss of deep tendon reflexes. Evidence suggesting sympathetic nervous system involvement includes the presence of diffuse swelling, changes in skin color and temperature, and hypersensitive skin and joint tenderness compared with the normal side. Relief of the pain with a sympathetic block is diagnostic. A guiding principle in evaluating patients with chronic pain is to assess both emotional and organic factors before initiating therapy. Addressing these issues together, rather than waiting to address emotional issues after organic causes of pain have been ruled out, improves compliance in part because it assures patients that a psychological evaluation does not mean that the physician is questioning the validity of their complaint. Even when an organic cause for a patient’s pain can be found, it is still wise to look for other factors. For example, a cancer patient with painful bony metastases may have additional pain due to nerve damage and may also be depressed. Optimal therapy requires that each of these factors be looked for and treated.
TREATMENT of CHRONIC PAIN
Once the evaluation process has been completed and the likely causative and exacerbating factors identified, an explicit treatment plan should be developed. An important part of this process is to identify specific and realistic functional goals for therapy, such as getting a good night’s sleep, being able to go shopping, or returning to work. A multidisciplinary approach that utilizes medications, counseling, physical therapy, nerve blocks, and even surgery may be required to improve the patient’s quality of life. There are also some newer, relatively invasive procedures that can be helpful for some patients with intractable pain. These procedures include implanting intraspinal cannulae to deliver morphine or intraspinal electrodes for spinal stimulation. There are no set criteria for predicting which patients will respond to these procedures. They are generally reserved for patients who have not responded to conventional pharmacologic approaches. Referral to a multidisciplinary pain clinic for a full evaluation should precede any of these procedures. Such referrals are clearly not necessary for all chronic pain patients. For some, pharmacologic management alone can often provide adequate relief.
ANTIDEPRESSANT MEDICATIONS
The tricyclic antidepressants (TCAs) are extremely useful for the management of patients with chronic pain. Although developed for the treatment of depression, the tricyclics have a spectrum of dose-related biologic activities that include the production of analgesia in a variety of clinical conditions. Although the mechanism is unknown, the analgesic effect of TCAs has a more rapid onset and occurs at a lower dose than is typically required for the treatment of depression. Furthermore, patients with chronic pain who are not depressed obtain pain relief with antidepressants. There is evidence that tricyclic drugs potentiate opioid analgesia, so they are useful adjuncts for the treatment of severe persistent pain such as occurs with malignant tumors. TCAs are of particular value in the management of neuropathic pain such as occurs in diabetic neuropathy and postherpetic neuralgia, for which there are few other therapeutic options. The TCAs that have been shown to relieve pain have significant side effects . Some of these side effects, such as orthostatic hypotension, cardiac conduction delay, memory impairment, constipation, and urinary retention, are particularly problematic in elderly patients, and several are additive to the side effects of opioid analgesics.
The serotonin-selective reuptake inhibitors such as fluoxetine (Prozac) have fewer and less serious side effects than TCAs, but they are much less effective for relieving pain. It is of interest that venlafaxine (Effexor), a nontricyclic antidepressant that blocks both serotonin and norepinephrine reuptake, appears to retain most of the pain-relieving effect of TCAs with a side-effect profile more like that of the serotonin-selective reuptake inhibitors. The drug may be particularly useful in patients who cannot tolerate the side effects of tricyclics.
ANTICONVULSANTS AND ANTIARRHYTHMICS
These drugs are useful primarily for patients with neuropathic pain. Phenytoin (Dilantin) and carbamazepine (Tegretol) were first shown to relieve the pain of trigeminal neuralgia. This pain has a characteristic brief, shooting, electric shock–like quality. In fact, anticonvulsants seem to be helpful largely for pains that have such a lancinating quality. A newgeneration anticonvulsant, gabapentin (Neurontin), is effective for a broad range of neuropathic pains.
Antiarrhythmic drugs such as low-dose lidocaine and mexiletine (Mexitil) can also be effective for neuropathic pain. These drugs block the spontaneous activity of damaged primary afferent nociceptors.
CHRONIC OPIOID MEDICATION
The long-term use of opioids is accepted for patients with pain due to malignant disease. Although opioid use for chronic pain of nonmalignant origin is controversial, it is clear that for many such patients opioid analgesics are the best available option. This is understandable since opioids are the most potent and have the broadest range of efficacy of any analgesic medications.
Although addiction is rare in patients who first use opioids for pain relief, some degree of tolerance and physical dependence are likely with long-term use. Therefore, before embarking on opioid therapy, other options should be explored, and the limitations and risks of opioids should be explained to the patient. It is also important to point out that some opioid analgesic medications have mixed agonist-antagonist properties (e.g., pentazocine and butorphanol). From a practical standpoint, this means that they may worsen pain by inducing an abstinence syndrome in patients who are physically dependent on other opioid analgesics.
With long-term outpatient use of orally administered opioids, it is desirable to use long-acting compounds such as levorphanol, methadone, or sustained-release morphine. Transdermal fentanyl is another excellent option. The pharmacokinetic profile of these drug preparations enables prolonged pain relief, minimizes side effects such as sedation that are associated with high peak plasma levels, and reduces the likelihood of rebound pain associated with a rapid fall in plasma opioid concentration. Constipation is a virtually universal side effect of opioid use and should be treated expectantly. It is worth emphasizing that many patients, especially those with chronic pain, seek medical attention primarily because they are suffering and because only physicians can provide the medications required for their relief. A primary responsibility of all physicians is to minimize the physical and emotional discomfort of their patients. Familiarity with pain mechanisms and analgesic medications is an important step toward accomplishing this aim.
Related article : Understanding Pain
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