Non-opioid pharmacologic treatments for acute pain Acetaminophen and NSAIDs In general, mild-to-moderate acute pain responds well to oral non-opioids (e.g., acetaminophen, NSAIDs, and topical agents). Although they are weaker analgesics than opioids, acetaminophen and NSAIDs do not produce tolerance, physical dependence, or addiction and they do not induce respiratory depression or constipation. Acetaminophen and NSAIDs are often added to an opioid regimen for their opioid-sparing effect. Since non-opioids relieve pain via different mechanisms than opioids, combination therapy can provide improved relief with fewer side effects. The choice of medication may be driven by patient risk factors for drug-related adverse effects (e.g., NSAIDs increase the rate of gastrointestinal, renal, and cardiovascular events). If acetaminophen or NSAIDs are contraindicated or have not sufficiently eased the patient’s pain or improved function despite maximal or combination therapy, other drug classes (e.g., opioids) are sometimes used. Non-opioid analgesics are not without risk, particularly in older patients. Potential adverse effects of NSAIDs include gastrointestinal problems (e.g., stomach upset, ulcers, perforation, bleeding, liver dysfunction), bleeding (i.e., antiplatelet effects), kidney dysfunction, hypersensitivity reactions, and cardiovascular concerns, particularly in the elderly. 109 The threshold dose for acetaminophen liver toxicity has not been established; however, the Food and Drug Administration (FDA) recommends that the total adult daily dose not exceed 4,000 mg in patients without liver disease (with a lower ceiling for older adults with certain conditions). 110 The FDA currently sets a maximum limit of 325 mg of acetaminophen in prescription combination products (e.g., hydrocodone and acetaminophen) in an attempt to limit liver damage and other potential ill effects of these products. 32 Topical agents Topical capsaicin and salicylates can both be effective for short term cutaneous pain relief and generally have fewer side effects than oral analgesics, but their long-term efficacy is not well studied. 111,,112 Topical aspirin, for example, can help reduce pain from acute herpes zoster infection. 107 Topical NSAIDs and lidocaine may also be effective for short-term relief of superficial pain with minimal side effects. Topical agents can be simple and effective for reducing pain associated with wound dressing changes, debridement of leg ulcers, and other sources of superficial pain. 103
Anticonvulsants
In a retrospective study of 12,840 elderly patients with arthritis, opioid use was associated with an increased risk relative to non-opioids for cardiovascular events, fracture, events requiring hospitalization, and all-cause mortality. 122 The risk of prolonged opioid use is particularly high after arthroscopic joint procedures. In a 2019 case-control study of 104,154 opioid-naïve adults, 8,686 (8.3%) developed new prolonged opioid use (continued opioid use between 91 and 180 days after shoulder arthroscopy). 123 Subgroups at higher risk for long-term use included women, those with a history of alcohol use disorder, those with a mood disorder, and those with an anxiety disorder. Opioid choices for acute pain If an opioid is deemed necessary to treat moderate-to-severe acute pain, the following general principles are recommended when starting an opioid: • Avoid extended-release and long-acting opioids such as methadone, fentanyl patches, and ER/LA versions of opioids such as oxycodone or oxymorphone. • Avoid co-prescribing opioids with other drugs known to depress central nervous system function (e.g., benzodiazepines) • Limit the dose and quantity of opioids to address the expected duration and severity of pain (usually less than 7 days). • Combine opioids with other treatments (e.g., non-pharmacologic options such as exercise or cognitive behavioral therapy, NSAIDs, or acetaminophen). • Closely monitor patients with impaired hepatic or kidney function if they are prescribed opioids, and adjust the dose or duration accordingly Immediate-release agents are strongly preferred because of the higher risk of overdose associated with ER/LA agents. A cohort study of 840,000 opioid-naïve patients over a 10-year span found that unintentional overdose was 5 times more likely in patients prescribed ER/LA agents compared to immediate-release opioids. 124 Opioid dosing for acute pain The amount of opioid prescribed should relate to the level of pain expected from the injury or procedure. Injuries or procedures involving bones and joints tend to be more painful than those involving soft tissues. 125 Table 3 illustrates the wide range of expected pain and associated recommended opioid doses for some common surgeries or procedures.
Anticonvulsants, gabapentin, pregabalin, oxcarbazepine, and carbamazepine, are often prescribed for chronic neuropathic pain (e.g., post-herpetic neuralgia and diabetic neuropathy) although evidence for efficacy in acute pain conditions is weak. 114 A 2017 trial, for example, randomized 209 patients with sciatica pain to pregabalin 150 mg/day titrated to a maximum of 600 mg/day vs. placebo for 8 weeks. 115 At 8 weeks there was no significant difference in pain between groups (mean leg pain intensity on a 0-10 scale 3.7 with pregabalin vs. 3.1 with placebo, P=0.19). such as Opioids for acute pain: use caution Opioids are commonly prescribed for pain, with nearly two thirds (64%) of the public reporting being prescribed an opioid for pain at some point in their lives. 116 However, this approach is not as safe and effective as once thought, and high-dose prescriptions or prolonged use not only increase the risk of misuse, addiction, or overdose, they may actually increase pain and pain sensitivity. 117,118 Recent evidence suggests that opioids may not be more effective for moderate to severe acute pain than non-opioid pain regimens. 119,120 A randomized trial of 416 patients with acute extremity pain found no clinically important differences in pain reduction at two hours after single-dose treatment with ibuprofen and acetaminophen vs. three different opioid and acetaminophen combination analgesics. 113 Physical dependence can readily occur after use of opioids at a sufficient dose (e.g., 30mg of oxycodone) for just a few days. In addition, side effects of opioid use can include constipation, confusion/gait instability, respiratory depression, pruritus, erectile dysfunction, and fractures, all of which may be more problematic in older patients and occur at higher rates than with non-opioid analgesics. A cross-sectional study compared common side effects experienced during the first week of treatment with opioid analgesics vs. non-opioid analgesics in patients over age 65 with acute musculoskeletal pain. 121 The intensity of six common opioid-related side effects were significantly higher with opioids. (A limitation of this study is that it could not assess severe but less common adverse events associated with NSAIDs and acetaminophen, including the risk for gastrointestinal bleeding, acute kidney injury, and hepatotoxicity.)
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