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Summary

Analgesic ladder: the original World Health Organization 3-step analgesic ladder has been modified to a 4-step ladder; 4-step ladder — patients can go up or down the ladder as their pain improves or worsens; the 4-step ladder incorporates invasive and minimally invasive nonpharmacologic treatments such as acupuncture and spinal analgesia

Categorization of pain: in addition to severity, pain can be categorized by type; somatic pain — can be localized to a specific area; treated with over-the-counter medications or nonnarcotic prescription agents; visceral pain — a more generalized deep-seated pain in the organs that may be treated with over-the-counter medicines along with opioids or adjuvant therapy; neuropathic pain — may be characterized as burning or shooting pain, numbness, or a pins-and-needles sensation; may be treated with nonsteroidal anti-inflammatory drugs (NSAIDs), which can help heal underlying inflammation, tricyclic antidepressants, antiepileptic drugs, and nerve blocks

Naproxen: naproxen (eg, Aflaxen, Aleve, Naprelan) stands out among NSAIDs because of its longer half-life; effect of ibuprofen (eg, Advil, Motrin, Nuprin) lasts 4–6 hr, whereas naproxen lasts 12 hr; less frequent dosing leads to better adherence; the regular dose of naproxen has been proven virtually equal in analgesia to morphine 10 mg intramuscular (IM)

Acetaminophen: the mechanism of action of acetaminophen involves both COX-2 inhibition and an increased release of endogenous cannabinoids; acetaminophen also seems to have some effect on inhibition of substance P, the body's most powerful neurotransmitter; the true maximum dose for acetaminophen on a daily basis is 4 gm, and the maximum recommended duration of using this dose is 4 days; the downside of acetaminophen is that it is the leading cause of hepatic failure; acetaminophen is also a common cause of overdose in adults; for patients who are at risk for acetaminophen toxicity (particularly those with a history of alcohol abuse or liver disease), the recommended maximum dose is 2 gm

Aspirin: aspirin irreversibly inhibits platelets, which differentiates it from other NSAIDs; patients who are taking aspirin before surgery need to stop aspirin 7 to 10 days before surgery to decrease the risk of bleeding; the other unique characteristic of aspirin is hypersensitivity, which is commonly associated with asthma; the genetically based “triad” is aspirin hypersensitivity, asthma, and nasal polyps; these patients tend to have allergies; enteric-coated aspirin helps patients tolerate it but does not reduce the incidence of gastric ulcers (the enteric coating dissolves after ingestion)

Pregnancy and breastfeeding: all NSAIDs should be avoided in the last 6 to 8 wk of pregnancy because they inhibit prostaglandins, which are required to keep the baby's ductus arteriosus open; both ibuprofen and naproxen are safe to use while breastfeeding

Side effects of NSAIDs: include blood pressure elevation, kidney failure, and elevated liver function tests (although liver failure is rare); indomethacin — should generally be avoided, especially in elderly patients, as it is associated with psychosis and central nervous system side effects; NSAIDs and proton pump inhibitors (PPIs) — combining an NSAID such as naproxen or ibuprofen with a PPI reduces the incidence of GI upset enough to make it similar to using a COX-2 inhibitor alone; however, taking PPIs for >1 yr increases risk for serious side effects such as Clostridium difficile infections, osteoporosis, Alzheimer disease, and gastric cancer; gastroenterologists now recommend a shorter course of PPIs of ≤3 mo and then shifting to an H2 blocker if necessary

COX-2 selective inhibitors: a newer class of NSAIDs; COX-1 and COX-2 are enzymes produced by the body; COX-1 promotes the gastric mucosa; COX-2 suppresses production of inflammatory prostaglandin, which is beneficial; however, the COX-2 enzyme also suppresses prostacyclin, one of the body's most powerful vasodilators, which potentially increases cardiovascular risk; COX-2 selective inhibitors are favorable for older patients because they are less likely to cause GI upset or clinically significant peptic ulcer disease than other NSAIDs; the COX-2 inhibitor meloxicam (Mobic, generic formulations) is higher on the pain efficacy scale than the older NSAIDs and is not overly COX-2 selective; ibuprofen is more COX-2 selective than naproxen, so naproxen has less cardiovascular risk (also rated higher in the chronic pain efficacy scale); naproxen is therefore favorable for patients with a history of myocardial infarction or stroke

GI effects of NSAIDs: the incidence of GI side effects is 10%–20%; GI bleeding — the incidence overall is <1%, but it is ≈1% in patients >75 yr of age; patients at increased risk for bleeding are patients >65 yr of age, patients with a history of peptic ulcer disease, and patients who are taking other agents (eg, steroids, anticoagulants) that increase risk; misoprostol (Cytotec, generic formulations) — GI protection is superior to that with a PPI or a COX-2 selective inhibitor, so it may be considered for patients prone to gastric bleeding

Ketorolac: the most effective nonopioid agent for pain relief, ketorolac has efficacy comparable to morphine; however, this potency comes at the cost of increased toxicity, so there is a 5-day prescribing limit due to the increased risk of renal and systemic toxicity

Topical NSAIDS: various diclofenac preparations; evidence supports 2 wk of effectiveness; price varies widely among types of preparations; diclofenac gel (Voltaren, generic formulations), drops, and patches are available; Cochrane Review from 2016 found that 60% of patients experienced ≥50% relief from pain; oral diclofenac is available, but topical diclofenac has only a 6% systemic exposure (safer in terms of GI toxicity)

Tricyclic antidepressants: neuropathic pain can be treated with drugs such as tricyclics and anti-epileptic drugs; these drugs may be effective by themselves, or they can be used to boost the effect of acetaminophen or NSAIDs; tricyclic drugs are on the Beers Criteria list of medications that may be inappropriate for older adults; for safety, prescribe at a low dose and prescribe that they be taken at bedtime; tricyclic antidepressants produce anticholinergic side effects; the tricyclic antidepressant associated with the least amount of anticholinergic effects is nortriptyline (Pamelor, generic formulations); tricyclic antidepressants have been found effective for managing pain over the long term in 1 of 3 patients

Bupropion (Wellbutrin, generic formulations): mechanism of action does not involve serotonin; a small study in 2001 found that 73% of patients found effective pain relief for a 6-wk period with bupropion; however, other agents have been more thoroughly studied

Duloxetine (Cymbalta, generic formulations): approved by the US Food and Drug Administration (FDA) for diabetic neuropathy, fibromyalgia, and chronic musculoskeletal pain; side effects include nausea and liver failure; more expensive than generic venlafaxine (Effexor), but venlafaxine produces changes on electrocardiography in 5% of patients

Gabapentin: used for neuropathic pain and diabetic neuropathy; gabapentin is also available in a more potent variant, pregabalin (Lyrica, generic formulations); it decreases anxiety, but it also produces euphoric effects and is classified as a Schedule V drug; gabapentin is one of the top 3 most commonly abused drugs in prisons in the US because it also apparently produces some euphoric effects and is not on the FDA list of scheduled drugs

Anticonvulsant drugs: carbamazepine (Tegretol, generic formulations) has an indication for trigeminal neuralgia; however, the side effects of anticonvulsants are problematic, and evidence is limited on the use of carbamazepine or topiramate (Topamax, generic formulations) for pain; Cochrane studies on the quality of research evidence led them to not recommend the use of anticonvulsants for chronic pain because of the limited benefits and high risk of adverse events

Tramadol: an isomer of morphine; chemically identical to morphine, but with less potential for addiction; it is a Schedule IV drug (has a potential risk for abuse); tramadol increases the risk of seizures and the risk of serotonin syndrome

Skeletal muscle relaxants: the most effective skeletal muscle relaxant is cyclobenzaprine (eg, Amrix, Fexmid, Flexeril); it has shown higher efficacy for musculoskeletal pain than naproxen, but not as effective as NSAIDs for acute back pain or chronic headache; it should not be used in older patients because of addictive potential and risk for falls

Topical analgesics: diclofenac — supported by evidence as the most effective topical medication; capsaicin — inhibits production of substance P; capsaicin cream (Zostrix, many generic formulations) is available over the counter; prescription capsaicin patch (Qutenza) has FDA indications for postherpetic neuralgia, HIV neuropathy, and diabetic neuropathy; lidocaine patch(eg, Dermalid, Lidoderm) — originally approved for knee arthritis; cream is also available and is less expensive

Oral steroids: limited evidence; most useful for herpes zoster; 40 mg/day ≤3 wk provides effective pain relief; also used for acute gout and back pain; side effects from use >3 mo include moon facies, fat accumulation in the neck (“buffalo hump”), obesity, striae, and osteoporosis; taper if using >40 mg/day long-term

Alternative treatments: include medical marijuana (use for chronic pain is now supported by evidence), turmeric, ginger, caffeine, aquatherapy, massage, tai chi, exercise, and cognitive behavioral therapy