Acute Pain Management in the General Population

JULY 17, 2018
Omama Zubairi, PharmD Candidate, and Deepali Dixit, PharmD, BCPS, BCCCP
Acute pain is one of the most common complaints that lead Americans to access the health care system, resulting in more than 115 million emergency department visits each year.1,2 Although there is no globally accepted definition for acute pain, it can be characterized by having an inciting event or stimulus, occurring suddenly, having a limited duration of less than 3 months to 6 months, and carrying the potential to develop into a pathologic condition.3,4 It can relate to skeletal or soft tissue damage and may be categorized as post-spontaneous or posttraumatic, with the trauma planned (surgical) or unplanned (accidental).3 Described as the body’s “awareness of noxious signaling from newly damaged tissue,” acute pain can lead to a variety of complications, including partial and total disability, reduced quality of life, and potential progression to chronic pain.5-7 In fact, it has been noted that poorly controlled postoperative pain is a major cause of chronic pain after surgery. Despite recent medical advances, acute pain is often undertreated, with most patients receiving inadequate pain control, leading to increases in health care costs and the length of stays in the hospital.8,9

Acute Pain Types
Pain can be characterized in a variety of ways, including duration (acute vs chronic) and location (joint related, neuropathic, and nociceptive). 8,9 Most acute pain can be described as nociceptive, as nociceptors are involved in the perception of pain, and their sensitization is a major cause of hyperalgesia. Although the exact substances released that result in the human perception of pain are not completely known, prostaglandins play a key role by sensitizing nociceptors.10 The perception of pain is primarily regulated by the central nervous system, which integrates afferent input from peripheral nociceptors, creating the perception of pain and further amplifying the input from peripheral nociceptors.4
Nociceptive pain can be further divided into 2 types: somatic and visceral. Visceral pain is a more diffuse type that is often described as gnawing and can be hard to localize.11 Nociceptive pain results from chemical, pressure, and temperature stimuli. This type of pain is also classified as originating from bones, connective tissue (somatic), internal organs (visceral), muscle, and skin. Somatic pain is much more direct and localized, occurring in the joints, skin, and subcutaneous tissue.11 This type of pain is often associated with an inflammatory process and therefore lends itself to treatment with an anti-inflammatory agent.

Treatment Goals
The immediate goals of treatment for patients suffering from acute pain include facilitating functional recovery and reducing pain to a tolerable level. Long-term goals include improving patients’ quality of life, reducing the risk of complications (eg, progression to chronic pain), and reducing overall health care–related costs.12 Multimodal treatment is crucial for optimizing pain relief. Because different modalities may be additive or synergistic, this approach can also reduce the potential for adverse effects (AEs). Analgesics, including acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), are most effective for treating acute pain because they target the natural inflammation that occurs with an injury.

Acetaminophen
Acetaminophen is a centrally acting agent with a variety of effects, including the decrease of prostaglandin synthesis, and is used as monotherapy for mild pain and an adjunct to therapy in moderate to severe pain. Results from studies have shown that acetaminophen provides similar analgesic control as NSAIDs for patients with mild to moderate pain.13-15 A recent Cochrane review noted that acetaminophen is preferred over NSAIDs as a first-line treatment because of the cardiovascular and gastrointestinal AEs of NSAIDs.16 Additionally, because of acetaminophen’s lack of effect on blood pressure, it is the analgesic of choice in patients with hypertension and renal impairment.17 Although this medication can be used in a wide patient population, it should be avoided in those with alcohol problems or liver disease.

NSAIDs
NSAIDs inhibit the cyclooxygenase enzymes decreasing prostaglandin synthesis, leadingto greater anti-inflammatory effects than acetaminophen, and are the agents of choice for acute pain because of prostaglandin-mediated inflammation. NSAIDs are preferred over acetaminophen for pain associated with dysmenorrhea and osteoarthritis.16,18 The results of a recent meta-analysis showed that individual NSAIDs differ in their analgesic properties from what was reported in previous studies, the results of which indicated that the individual drugs shared similar analgesic relief. Patients contending with bleeding disorders, coronary artery disease, gastroesophageal reflux disease, peptic ulcers, renal impairment, or stroke should avoid NSAIDs.

COX-2 Inhibitors
The use and role of cyclooxygenase-2 (COX-2) inhibitors in clinical practice are minimal because of several unresolved questions. Although these drugs have a similar efficacy as nonselective NSAIDs, the main concern for the use of COX-2 inhibitors is safety. The inhibitors have been associated with an increased risk of cardiovascular events. Celecoxib may be considered in select patients because it does not affect platelet function or directly increase the risk of bleeding.

Tramadol
Tramadol is a weak opioid agonist with 2 mechanisms of action: binding to the opioid μ receptor and inhibiting the reuptake of norepinephrine and serotonin. Tramadol theoretically possesses weak opioid activity, reducing the risk of respiratory depression. However, tramadol is a substrate for the CYP2D6 liver enzyme, so agents with the ability to induce or inhibit this enzyme may interact with tramadol. Clinicians should exercise caution in patients concurrently on selective serotonin reuptake inhibitors because of the risk of precipitating serotonin syndrome. There is a lack of evidence for the benefit of tramadol.19 However, no evidence supports the concept that tramadol is less addictive than opioids.

Topical Analgesics
Camphor, menthol, methyl salicylate, and a combination of these can be useful in managing localized musculoskeletal injuries, particularly if they can be rubbed into the affected area. These agents can provide short-term relief of muscle pain. Many products are available over the counter and are inexpensive. However, they must be applied several times per day on intact skin. Furthermore, topical NSAIDs, such as diclofenac patches and gel, can also provide good pain relief and are generally underused, particularly in elderly adults.20 

Opioids
For moderate to severe pain, opioids are a mainstay of therapy because they produce greater analgesia effects than acetaminophen and NSAIDs. Results from 2 recent studies measuring postoperative pain showed that combination treatment with a nonopioid analgesic such as acetaminophen produced superior analgesia compared with the opioid alone.21,22 There is limited evidence on whether AEs of the different agents vary at equianalgesic doses.23 In addition, in a meta-analysis, there was limited evidence to point to any individual agent that was more effective than morphine in reducing cancer-related pain, and because of a lack of studies comparing opioid agents in acute pain, a similar statement can be made.24

WHO Pain Ladder
Developed in 1986 to treat cancer pain, the World Health Organization (WHO) pain ladder is a validated instrument that is the backbone of pain management.25-27 Consisting of 3 steps ascending in the degree of pain severity, the pain ladder recommends specific pharmacologic treatments for each level of pain.25-27 It is also important to note that regardless of step, adjuvant therapy ranging from calcium channel blockers to tricyclic antidepressants is recommended as an add-on for additional pain relief. Adjuvants enhance the effects of nonopioid and opioid analgesics by targeting pain through a different mechanism, establishing the pain ladder’s alignment with the therapeutic strategy of multimodal analgesia.
For step 1, characterized as mild pain, treatment should consist of nonopioid analgesics including acetaminophen and NSAIDs. Patients inadequately controlled under step 1 or who have a more severe baseline level of pain should proceed to step 2 in the WHO pain ladder, which is labeled moderate pain. This step recommends therapy with a low-potency opioid, such as codeine or oxycodone, in combination with a nonopioid such as acetaminophen or an NSAID. Combinations of acetaminophen-containing opioid products can also be used to lessen the pill burden for patients. The third step, or the severe pain category, is for patients who are inadequately controlled by step 2 therapy. Patients in this category should be treated with a high-potency opioid, such as fentanyl, hydromorphone, or morphine, in combination with a nonopioid analgesic.

Balancing Opioid Drug Abuse With Pain Management
Because of the addictive properties of opioid analgesics, these medications can be abused. Results from a 2010 survey showed that an estimated 2 million people used prescription pain medications for nonmedical purposes.28 In the heat of the opioid epidemic, health care professionals face a difficult situation. However, it is important to realize that health care professionals can take small steps to reduce diversion and improve patient outcomes. Such steps include prescribing the minimally effective dose for opioids and encouraging patients to use 1 pharmacy for their medications.

Conclusion
Acute pain is a prevalent condition and has a significant impact on morbidity, quality of life, and health care costs in the United States. Acute pain management should focus on a multimodal approach of using medications of different classes to provide the best outcomes for patients.
 
Omama Zubairi is a PharmD candidate at the Ernest Mario School of Pharmacy at Rutgers University in Piscataway, New Jersey. Deepali Dixit, PharmD, BCPC, BCCCP, is a clinical associate professor at the Ernest Mario School of Pharmacy at Rutgers University. She is also a clinical pharmacy specialist, critical care, at Robert Wood Johnson University Hospital in New Brunswick, New Jersey.

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