Medication Guide for Pain—A Short Primer for Primary Care
There are several classes of medications available for the treatment of chronic, noncancer pain, depending on the classification, duration, and severity of pain a patient is experiencing.
Nociceptive pain, which is pain in muscles, joints, or tissues that occurs due to injury, is typically described as dull, aching, or throbbing. In contrast, neuropathic pain, which involves abnormal signaling in the nerves as a result of injury or damage to the brain, spinal cord, or the peripheral nerves, is usually described as sharp, burning, tingling, or numbing.
Acute pain is defined as pain that lasts less than 3 months and is associated with an identifiable cause, whereas chronic pain may or may not have an identifiable cause, lasts beyond the typical course of an illness or injury (usually 6 months or less), and negatively impacts a patient’s quality of life.1 Chronic pain can be a mixture of both nociceptive and neuropathic pain.
Medications can help reduce pain, but they may not be able to eliminate it. Medications also are associated with adverse events (AEs) that can negatively impact a patient’s quality of life. Each patient’s response to and tolerance of a pain medication is unique, and use of certain pain medications may be limited or even contraindicated due to a patient’s comorbidities, concurrent medications, and renal and/or hepatic impairment.
Therefore, medications are recommended as a component of an interdisciplinary approach to chronic pain management with continual re-evaluation of the risks and benefits of continued use.2
Patients should be counseled about realistic expectations related to potential pain relief, possible AEs, expected duration of therapy (some medications may need to be initiated at doses below the therapeutic level and gradually titrated to minimize AEs), and plans for discontinuation due to intolerable AEs, lack of adequate response, or aberrant behaviors when applicable.
The medications used for chronic, noncancer pain management are broadly classified as non-opioids, adjuvants, topical analgesics, muscle relaxants, and opioids (Table).
Non-opioid medications, such as acetaminophen (Tylenol, others), aspirin (Bayer, Bufferin, others), and non-steroidal anti-inflammatory drugs (NSAIDs), are indicated for the treatment of mild to moderate nociceptive pain. For acute, subacute, and chronic low back pain, both acetaminophen and NSAIDs can be recommended, in addition to self-care and non-pharmacologic therapies such as cognitive behavioral therapy, exercise, massage, and yoga.2
Acetaminophen is available both over-the-counter (OTC) and as a prescription in combination with opioids. For adults, acetaminophen can be taken 4 to 6 times a day as long as the total amount taken per day does not exceed 3,000 mg due to risk of liver toxicity.1 Under the supervision of a prescriber, up to 4,000 mg of acetaminophen can be taken per day. However, patients with chronic liver disease should be prescribed lower maximum doses (2,000 mg/d). Since hundreds of OTC products contain acetaminophen, it is important for patients to keep track of the total daily amount ingested from all sources.3
Acetaminophen is not recommended for patients with a history of alcohol abuse, and patients should not consume alcohol while using acetaminophen. Patients also should avoid acetaminophen if they have a history of phenylketonuria.4
Aspirin and NSAIDs
Unlike acetaminophen, aspirin and NSAIDs have anti-inflammatory properties and are used widely for arthritis, low back pain, and other musculoskeletal disorders. Aspirin and select NSAIDs, such as ibuprofen (Advil, Motrin, others) and naproxen (Aleve, Naprosyn, others), are available OTC, whereas the majority of NSAIDs require a prescription.
NSAID use should be limited to the lowest dose and shortest duration due to the risk of gastric distress, ulceration, bleeding, increased risk of cardiovascular events, and kidney toxicity. To address these concerns, pharmaceutical companies have been investigating new delivery systems. Recently, Iroko Pharmaceuticals has gained approval of three new formulations of NSAIDs that use "SoluMatrix Fine Particle Technology" that contains submicron particles of the NSAID that are approximately 10 times smaller than their original size. This smaller particle size provides an increased surface area, leading to faster dissolution, thus "allowing clinicins to prescribe the lowest effective dose of NSAIDs for the shortest possible duration," noted the company. The three new products include Vivlodex (meloxicam), Zorvolex (diclofenac) and Tivorbex (indomethacin).
Up to 25% of chronic NSAID users will develop ulcer disease and 2% to 4% will have a gastrointestinal (GI) bleed or perforation.4 Strategies to decrease GI risk include prescribing a proton-pump inhibitor or misoprostol (Cytotec, others) along with the NSAID, or prescribing the cyclooxygenase-2 (COX-2)–selective NSAID celecoxib (Celebrex).3
However, patients taking antiplatelet therapy, such as low-dose aspirin for cardioprotection, should consult their provider prior to initiating an NSAID regimen, especially a COX-2 inhibitor, because chronic NSAID use can diminish aspirin’s cardioprotective effects, which can increase the risk of cardiovascular events. Providers should evaluate patients for cardiovascular and GI risk prior to initiating an NSAID for chronic pain management.
Adjuvant Pain Treatments
Medications that are indicated for the treatment of other conditions have also been studied for the treatment of chronic neuropathic pain—for example antidepressants and anticonvulsants.
Tricyclic antidepressants (TCAs), including amitriptyline (formerly sold as Elavil), desipramine (Norpramin, others), and nortriptyline (Pamelor, others), were the first antidepressants recommended for treatment of chronic pain conditions, including diabetic neuropathy, post-herpetic neuralgia, migraine prophylaxis, and subacute or chronic low back pain.2,5-7
An adequate trial of an antidepressant for chronic pain occurs over 4 to 8 weeks at a therapeutic dose. Unfortunately, many patients are unable to tolerate TCAs due to their dose-related anticholinergic AEs, including sedation, constipation, urinary retention, blurry vision, and dry mouth.
TCAs should be used with caution in elderly patients because they may increase the risk of falls. Patients with a history of cardiac disease also should be cautious because TCAs increase the risk of QT prolongation. Practitioners should obtain a baseline electrocardiogram for patients aged older than 40 years and limit the TCA dose to less than 100 mg per day if possible.5