1

What is pain?

Pain is a complex sensory and emotional experience. It is unpleasant by definition and inherently subjective. Nociception is the perception of painful, actual or threatened, tissue damage. In response to painful stimuli, people exhibit pain behaviors that are influenced by age, developmental status, comorbid conditions, and other biopsychosocial factors.

2

What are various age-appropriate ways to measure pain?

Many validated scales exist to measure nociception or pain behaviors.

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  FLACC: A commonly used pain scale for infants, children, and people with cognitive impairment who have trouble communicating. FLACC is an abbreviation and mnemonic for F aces, L egs, A ctivity, C ry, and C onsolability. Each section is scored 0–2 for a possible total of 10 points.

  
  
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  Wong-Baker FACES scale: An instrument validated for children as young as 3 years, as well as children and adults with cognitive delay. Six faces (scores of 0–5) of progressive discomfort are displayed, and patients pick the face that corresponds to their pain. To extrapolate the scale, the score is doubled to create a 10-point scale.

  
  
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  Numeric Rating Scale (NRS): The most commonly used self-report scale; patients pick a number on a scale from 0 (“no pain”) to 10 (“the worst pain imaginable”). This is validated in children as young as 5 years who have a concept of numbers (i.e., “5 is larger than 1”).

3

What is the difference between acute and chronic pain?

Pain can be divided into acute pain and chronic pain. Acute pain is defined by self-limited pain of <3–6 months’ duration. Chronic pain is defined as pain lasting longer than 3–6 months, or longer than expected for the mechanism of injury. The approaches to acute and chronic pain differ, and an in-depth approach to treating chronic pain is beyond the scope of this chapter.

4

How can classifying pain help guide treatment?

Pain descriptors and patterns can help discern the underlying injury. There are many taxonomies of pain; however, they are broadly classified as nociceptive, neuropathic, psychogenic, and mixed. Nociceptive pain is pain associated with tissue injury (e.g., surgery or fracture), inflammation (e.g., rheumatoid arthritis or ankle sprain), or tumor. Neuropathic pain is broadly classified to involve both direct nerve injury (i.e., amputation or trauma), central nervous system (CNS) injury (i.e., spinal cord injury or post-stroke pain), or altered nerve activity (i.e., functional pain). Psychogenic pain is pain existing without discovered anatomic tissue injury and in a distribution inconsistent with other functional causes. Most types of acute pain are nociceptive, and most causes of chronic pain have mixed etiologies.

5

What is the general approach to acute pain?

Acute pain is best treated with medications that target the underlying cause of pain. Effective treatments include nonsteroidal antiinflammatory drugs (NSAIDs), acetaminophen, local anesthetics, general anesthetics, muscle relaxants, and opioids. The World Health Organization (WHO) pain ladder ( Fig. 50.1 ) is an effective framework for treating acute and cancer-related pain. For pain with a predictable trajectory, scheduled dosing of nonopioid medications is preferred. These strategies can help prevent opioid use, or reduce total opioid dose if they are required. This concept is called opioid-sparing strategies .

World Health Organization (WHO) Pain Relief Ladder for Adults.

A useful strategy is to continue weak analgesics when stepping up to stronger medications. Weak analgesics can be scheduled to reduce the need and total dose of opioids.

6

How do NSAIDs work?

NSAIDs inhibit the enzyme cyclooxygenase (COX), which produces prostaglandins that contribute to inflammation. This causes pain by sensitizing nerve terminals to injury. Thus, NSAIDs are useful for decreasing inflammation and are generally considered weak analgesics. COX-1 and COX-2 are differentially produced. Most tissues constitutively produce COX-1, and COX-2 is induced by inflammation.

7

What are the differences between NSAIDs?

NSAIDs are more similar than they are different. Nonselective NSAIDs have similar predictable side effect profiles based on their COX-2/COX-1 inhibition. Also, NSAIDs differ in their duration of action. COX-2 inhibitors (“Coxibs”) were designed to minimize the long-term side effect profile of this medication class, but unfortunately were associated with a possible increase in the risk of myocardial infarction and thrombotic strokes with prolonged use. The only COX-2 inhibitor currently approved for use in the United States is celecoxib.

8

What are the principal adverse effects of long-term NSAID therapy?

The frequency of side effects is often associated with COX-2/COX-1 inhibition ( Table 50.1 ):

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  Gastrointestinal (GI) effects: Gastritis, peptic ulcer disease ( Table 50.2 ), diarrhea, GI hemorrhage

  
  
  
  

  Table 50.2

  
  

  Cumulative Prevalence of GI Ulcers after 12 Weeks of NSAID Therapy without GI Protection

  
  

  
  
  
  
  
  
  
  
  
  
  
  

  Celecoxib (200 mg bid)	8.5%
  Naproxen (500 mg bid)	40.7%
  Ibuprofen (800 mg tid)	28.5%

   
  

  bid, Twice a day; GI, gastrointestinal; NSAID, nonsteroidal antiinflammatory drug; tid, three times a day.
  
  
  
  
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  Renal effects: Decreased renal blood flow, decreased glomular filtraon rate (GFR), salt and water retention, acute papillary necrosis, chronic interstitial nephritis

  
  
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  Hematologic effects: Inhibition of platelet aggregation, increased bleeding time

  
  
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  Pulmonary effects: Bronchospasm

  
  
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  Hepatic effects: Elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT), drug-induced hepatitis

  
  
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  Idiopathic reactions: Vasomotor rhinitis, angioedema, hypotension, drug-induced rash

9

Which is the best NSAID to use?

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  No NSAID is clearly better than another, although subtle differences may make one more preferable for a specific reason. Table 50.3 lists typical doses and useful notes about select NSAIDs. Factors that influence choice include route of administration, desired dosing interval, COX selectivity, and special considerations.

  
  
  
  

  Table 50.3

  
  

  Suggested Dosing and Useful Notes for Common NSAIDs

  
  

  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

  Drug	Dose (mg/kg)	Duration	Routes	Notes
  Ibuprofen	400–800 mg (4–10 mg/kg)	4–8 h	IV, PO	PO form inexpensive and available OTC. For use >6 months old
  Naproxen	250–500 mg (5 mg/kg)	8–12 h	PO	Inexpensive often started with a loading dose in adults
  Diclofenac	50 mg (1 mg/kg)	8 h	PO, TOP	Inexpensive; often used with a loading dose in adults. Topical gel available.
  Ketorolac	15–30 mg IV, 60 mg IM once (0.5 mg/kg IV or 0.1 mg IM once)	8 h	IV, IM, PO	Potent analgesic; use for <5 days. PO generally used only for IV continuation. Consider 50% dose reduction in critical illness. For use >8 months and 8 kg.
  Indomethacin	25–50 mg (0.5–1 mg/kg)	6–12 h	PO	Max dose of 200 mg/day for adults, 4 mg/kg for children. Use in children limited; alternative use is preferred.
  Meloxicam	5–10 mg (0.125 mg/kg)	24 h	PO	Capsules and tablets are not interchangeable, even if dose is equal.
  Celecoxib	100–200 mg 10–25 kg–50 mg 25–50 kg – 100 mg	12–24 h	PO	Best GI profile and use with platelet disorders. May increase risk of thrombosis and myocardial infarction.

   
  

  IM, Intramuscularly; IN, intranasally; IV, intravenously; NSAIDs, nonsteroidal antiinflammatory drugs; OTC, over the counter; PO, orally; TOP, topical.
  
  
  
  
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  Intravenous (IV) ketorolac is very potent, and therapeutic doses are often described as producing analgesia equivalent to typical doses (10 mg or 0.1 mg/kg) of IV morphine. This is accompanied with a higher than typical adverse effect profile, and use should not exceed 5 days.

10

How is acetaminophen different from typical NSAIDs?

Acetaminophen has an unclear mechanism of action and different elimination and side effect profile. However, it also contains both analgesic and antipyretic activity. It can be safely used in combination with all NSAIDs.

11

What side effects are associated with acetaminophen?

Acetaminophen is not associated with the GI or renal effects of NSAIDs. The most concerning side effect is hepatotoxicity. Acetaminophen-induced hepatotoxicity can be life threatening. It is influenced by dose, duration of use, and comorbid conditions such as hepatic disease or malnutrition.

12

What are the safe dose ranges for acetaminophen?

Acetaminophen is safe and effective at doses of 650–1,000 mg every 4–6 hours in adults, and 10–15 mg/kg for infants and children. Rectally administered acetaminophen should be dosed as 15 mg/kg due to reductions in bioavailability. The maximum recommended daily dose is 4 g/day for adults and 75 mg/kg/day for infants and children.

13

What are toxic doses of acetaminophen?

Toxicity depends on multiple factors, including dose, duration of use, and comorbid conditions. Single dose toxicity is unlikely at doses below 7.5–10 g for adults or 150 mg/kg for infants and children. Chronic administration can produce toxicity at any dose at or above the maximum recommended daily dose.