Pain management

Pain is an unpleasant sensory and emotional experience that arises from actual or potential tissue damage. There are a number of ways to differentiate pain, the most common of which is the distinction between acute and chronic pain. Acute pain is a warning signal for actual or potential tissue damage and is associated with trauma, surgery, and illness. Chronic pain is generally defined as pain lasting beyond the normal tissue healing time. Standardized pain intensity scales are used to evaluate pain in a clinical setting. Pain management involves a multimodal approach with analgesic drugs, physical therapy, behavioral therapy, as well as interventional and surgical methods. The management of chronic pain follows the WHO analgesic ladder, a three-step algorithm and set of guiding principles based on using pharmacologic agents sequentially, escalating from nonopioids for mild pain to strong opioids for severe pain, in accordance with the degree of pain as reported by the patient. Each step of the ladder consists of regular medication and PRN medication as needed. If the analgesic effect is not sufficient at a certain level of the WHO ladder, advancing to the next step must be considered. Independent of the step, additional adjuvant drugs may be administered to potentiate analgesia and manage side effects of the analgesic drugs.

Definitions

• Pain (according to the International Association for the Study of Pain; IASP): “Pain is an unpleasant sensory and emotional experience arising from actual or potential tissue damage, or described in terms of such damage. [...] Pain is always subjective.” ^[1]
• Acute pain
  • A warning signal indicating actual or potential tissue damage that triggers a protective reaction.
  • Typically associated with trauma, surgery, and acute illness.
• Chronic pain
  • Pain that lasts beyond the normal tissue healing time; (6 months according to the IASP )
  • Unlike acute pain, chronic pain has no protective role in preventing further tissue damage and can be considered a disease entity in its own right.

Types of pain ^[2]

• Nociceptive pain: pain that is triggered by chemical, mechanical, or thermal stimuli (noxious stimuli)
  • Somatic pain (musculoskeletal pain): localized, sharp pain that varies in duration and quality (Aδ fibers)
  • Visceral pain: dull, diffuse, deep pain (C fibers)
• Neuropathic pain: pain caused by abnormal neural activity that arises secondary to injury, disease, or dysfunction of the nervous system
  • Central pain: caused by CNS dysfunction; (e.g., from lesions produced by an ischemic stroke, phantom limb pain)
  • Peripheral pain: caused by damage to peripheral nerves; (e.g., diabetic neuropathy, postherpetic neuralgia)
  • Sympathetically mediated pain: caused by damage to autonomic nerves (e.g., complex regional pain syndrome)
• For an overview of pain symptoms in patients with serious or life-threatening illnesses, see “Pain concepts in palliative care”.

Physiology ^[3]

• Pain pathway: nociceptors detect a chemical, mechanical, or thermal noxious stimulus → conversion of stimulus to an electric signal (action potential): → C fibers and Aδ fibers carry afferent input to the dorsal horn of the spinal cord → secondary nociceptive neurons in the spinothalamic tract carry afferent input to the thalamus in the CNS → pain perception and a response sent along efferent pathways, which results in pain modulation and/or a reaction
• Withdrawal reflex: A polysynaptic spinal reflex that causes a part of the body to move away from a painful stimulus (e.g., a hot object) via contraction of flexor muscles and relaxation of extensor muscles

Sensitization ^[4][5]

• Abnormal pain perception due to increased neuronal sensitivity to noxious stimuli (hyperalgesia) and/or reduced neuronal threshold to otherwise normal stimuli (allodynia) in response to local injury, inflammation, and/or repetitive stimulation.
• Plays a major role in the generation and maintenance of chronic pain and neuropathic pain (e.g., postherpetic neuralgia)
• Although not completely understood, the pathophysiology is thought to involve the following two mechanisms:
  • Peripheral sensitization
    • Injury, inflammation, or repetitive stimulation of the peripheral nociceptive neurons → local release of chemical mediators (e.g., cytokines, nerve growth factors, histamine)→ repeated or prolonged exposure to chemical mediators upregulates the ion channels in the nociceptors → increases sensitivity and/or reduces threshold to chemical mediators even further → increased action potentials → abnormal pain perception
    • Usually ceases once the tissue injury or inflammation heals
  • Central sensitization
    • Injury and/or inflammation of the CNS (e.g., dorsal horn of the spinal cord, brain) → increased excitability and reduced inhibition in the CNS and recruitment of non-nociceptive fibers (e.g., Aβ fibers) into the nociceptive pathway → abnormal pain perception
    • Chronic peripheral pain disorders can be a significant driver to the sensitization of central nociceptive neurons
    • Usually continues even after the initial injury has healed

• Definition: pain that is perceived at a location other than that of the causative stimulus; projection of pain usually onto a specific dermatome or myotome of the corresponding segment of the spinal cord
• Common examples of referred pain
  • Right shoulder pain in patients with cholecystitis or perforated PUD
  • Kehr sign: left shoulder pain associated with diaphragmatic irritation resulting from hemoperitoneum (classically secondary to splenic rupture)
  • Left-sided chest and arm pain: myocardial infarction
  • Periumbilical pain in the early stages of appendicitis
• Treatment: Select treatments may reverse this pathway.

References:^[6][7][7][8]

• Definition
  • Phantom sensation: sensation that the amputated limb is still partially or totally existent
  • Phantom pain: sensation of pain in an amputated limb
    • Intermittent pain of varying character (e.g., burning, tingling, shooting, itching, squeezing)
    • Onset usually within days to weeks after amputation; pain often resolves or lessens over time
• Incidence: common complication after upper or lower extremity amputation
• Diagnosis: diagnosed only after exclusion of other causes of stump pain
• Treatment: multimodal approach
  • Mirror therapy
  • Transcutaneous electrical nerve stimulation: an analgesic therapy used to modify pain perception by administering continuous electrical impulses via electrodes on the skin
  • NMDA receptor antagonists
  • Adjuvant therapy (e.g., tricyclic antidepressants, anticonvulsants)
• Prophylaxis: perioperative regional anesthesia

References:^[9]

To optimize pain management, a thorough history and assessment of pain is required prior to initiating treatment.

• Pain characteristics (location, quality, temporal aspects, triggers)
• Associated symptoms (changes in mobility and strength)
• Pain impact (on daily life, sleep, activities)
• Previous pain assessments and/or treatment
• Pain intensity scale: subjective grading of pain severity by the patient
  • Numeric rating scale (NRS): most common pain scale, evaluates pain on a scale from 0–10
  • Visual analog scale (VAS): visual equivalents suitable for children
  • Verbal descriptor scale
• Pain diary: regular documentation of the pain intensity to identify peaks and triggers; enables treatment optimization

Pain can be difficult to assess in nonverbal patients; obtain supporting information from caretakers and use a specialized pain score, e.g., the nonverbal pain scale.

Be aware of implicit bias in the assessment of pain: Hispanic and Black patients are less likely to receive any and/or appropriate analgesia compared to White patients, even when reported pain scores are identical. ^[10][11]

Pain is subjective! Pain scales are used to assess a patient's pain and response to pain management over time. They cannot be used to compare pain intensity between patients.

References:^[12]

WHO analgesic ladder

The WHO analgesic ladder is a 3-step algorithm for the management of acute and chronic pain.

• Regular analgesic (modified-release drugs, administered at fixed times and doses)
  • By the mouth: preferably, analgesics should be given orally.
  • By the clock: regular administration at fixed times, rather than on demand
  • By the ladder (symptom-oriented): if the patient is still in pain, it is necessary to go up a step
• Appropriate PRN medication
  • Short-acting analgesics for peaks in pain
  • If PRN medication is required ≥ 3×/day → inadequate analgesia likely; review the regular medication
• Additionally, concurrent treatment with adjuvant drugs

Nonopioid analgesics are first-line agents for pain; prescribe them alone for mild to moderate pain and in combination with opioids for severe pain. ^[14]

For both opioid and nonopioid analgesics, use the minimal effective dose for the shortest duration of time to minimize adverse effects. Pain intensity scales should be used in regular intervals to assess the success of pain management.

Oral analgesics

All patients being discharged with opioid medications should receive counseling on the use of prescription opioids.

Parenteral analgesics

Analgesic suppositories

• Acetaminophen
• Indomethacin
• Aspirin

Topical analgesics

Adjuvant analgesics

Anticonvulsants

Anticonvulsants are useful adjuncts in the management of neuropathic pain. They typically will not be helpful for acute pain, rather are more commonly used for chronic neuropathic pain.

• Gabapentin
• Pregabalin
• Carbamazepine

Muscle relaxants

Consider muscle relaxants in patients with pain associated with muscle spasticity.

• Cyclobenzaprine
• Methocarbamol
• Baclofen

Avoid prescribing opioids, benzodiazepines, or muscle relaxants (alone or in combination) for treatment of acute nontraumatic low back pain. These agents do not improve pain outcomes and can increase the risk of harm. ^[24][25]

Antidepressants

Tricyclic antidepressants and SNRIs can be helpful for chronic pain syndromes and neuropathic pain. Antidepressants for chronic or neuropathic pain are recommended by the American Society of Anesthesiologists in their 2010 guideline, but only duloxetine is FDA-approved for this indication. All others are off-label use. ^[26][27]

• Tricyclic antidepressants
  • Amitriptyline ^[28]
  • Doxepin
  • Clomipramine
• SNRIs
  • Duloxetine
  • Venlafaxine

Intravenous patient-controlled analgesia

• Infusion pump designed to release additional IV medication in response to patient's request
• Indication: severe acute pain that is difficult to manage and is expected to be limited in duration

Management of side effects

• Laxatives (see constipation)
• Antiemetics
• Proton-pump inhibitors (PPIs): Consider in patients taking frequent NSAIDs.

There are a number of procedures available that complement the pharmacologic management of pain.

• Regional anesthesia: infiltration with local anesthetics (e.g., lidocaine)
• Physical therapy
  • Massage
  • Thermotherapy
    • Involves the application of heat to joints, muscle, and/or soft tissue (e.g., using hot cloths, ultrasound, heating pads, warm compresses).
    • Used to relieve pain and induce muscle relaxation.
  • Desensitization techniques
  • Osteopathic manipulative treatment (OMT): a technique used by osteopathic physicians to relieve pain through stretching, gentle pressure, and resistance
• Acupuncture
• Behavioral therapy
  • Relaxation techniques
    • Biofeedback therapy
    • Autogenic training
    • Progressive muscle relaxation (Jacobson's technique)
  • Cognitive behavioral therapy
  • Patient education

References:^[29][30]

• Background ^[31]
  • Pain pathways are developed by the 20^th week of gestation.
  • Newborn and preterm infants are sensitive to pain and stress.
  • Procedural pain
    • Pain and stress that occur as a result of medical procedures, e.g., IV cannulation, venipuncture, finger prick, heel lance, lumbar puncture, bone marrow aspiration
    • Common in pediatric ICU patients, preterm neonates, children with malignancy
  • Nociceptive stimuli induce behavioral, autonomic, and hormonal responses in infants similar to those seen in older individuals.
  • Chronic or recurrent exposure to nociceptive stimuli can result in sensitization of the maturing neuronal pathways → hypersensitivity to pain
• Clinical features
  • Facial grimacing
  • Crying
  • Changes in crying pattern
  • Inconsolableness
  • Irritability
  • Changes in sleep pattern
• Neonatal pain assessment
  • Scoring systems for acute and postoperative pain in infants evaluate physiological parameters , behavioral changes , and/or contextual factors.
  • Examples: premature infant pain profile (PIPP), neonatal infant pain scale (NIPS), neonatal pain agitation sedation scale (N-PASS), crying, requires oxygen saturation, increased vital signs, expression, sleeplessness (CRIES) score
• Management: neonatal pain ladder ^[31][32]
  • Principles
    • Appropriate analgesia according to the stages of the WHO analgesic ladder
    • Preemptive analgesia for painful procedures administered before, during, and after the procedure
    • Regular assessment of the severity of pain and response to analgesia
    • The choice of the step depends on the anticipated intensity of pain
    • Steps can be combined if single measures are insufficient.
  • Analgesic steps
    • Step 1: nonpharmacological measures, e.g., breastfeeding, use of a pacifier, skin-to-skin contact, oral sucrose
    • Step 2: topical analgesia (e.g., topical lidocaine, tetracaine gel)
    • Step 3: oral, rectal, or IV administration of acetaminophen or NSAIDs
    • Step 4: IV infusion of opioids
    • Step 5: subcutaneous infiltration of lidocaine or specific nerve blocks
    • Step 6: sedation or general anesthesia

Acute pain ^[33]

Tailor pain management to the underlying condition.

Approach

• Provide prompt analgesia to patients presenting with acute, severe pain.
• Assess pain severity and analgesics used.
  • Use a pain intensity scale.
  • Document recent analgesic use (e.g., type and dosage of medication).
  • Reassess pain severity every hour or sooner if necessary.
• Provide treatment.
  • Give NSAIDs and acetaminophen if not contraindicated.
  • Offer an oral opioid or combination analgesic if NSAIDs and acetaminophen are insufficient or contraindicated.
  • Consider a subanesthetic ketamine infusion as a stand-alone treatment or an adjunct to opioids. ^[34]
• Administer ice, elevation, and immobilization as indicated.
• Provide condition-specific treatment.
• Limit ambulatory opioid prescriptions to < 3–5 days and provide counseling on the use of prescription opioids.

Additional treatment considerations

• Offer parenteral analgesics to patients with an obvious acute deformity or suspected dislocation.
• Consider local and regional anesthesia for localized pain.
• For emergency procedures, consider analgesics for procedural sedation.

Administer acute pain management promptly. Withholding acute pain management does not improve the accuracy of a physical examination.

In the emergency department, pain is frequently undertreated in children, patients with a different cultural or linguistic background from their provider, and patients with neurocognitive disorders, because of communication difficulties, atypical presentations, and implicit bias. ^[33]

Acute exacerbations of chronic pain

• Management of acute-on-chronic pain requires significant empathy and skill.
• The goal is a return to baseline function, not the complete alleviation of pain.
• Follow local departmental policies if available.
• Obtain a detailed pain assessment.
• Assess for reversible causes of pain.
• If no reversible cause of pain is determined:
  • When possible:
    • Review any existing individualized comprehensive pain management plan.
    • Discuss care with the patient's outpatient health care provider.
  • Offer NSAIDs and acetaminophen if not contraindicated.
  • Consider the addition of adjuvant analgesics.

Avoid routinely prescribing opioids for acute exacerbations of chronic pain. Local guidelines may, however, support the use of opioids in patients with advanced malignancy. Involve the patient's regular health provider in treatment decisions whenever possible.

Pain in sickle cell disease may represent a vasoocclusive event; manage new pain aggressively and perform a full diagnostic workup.

Assessment of pain in the ICU

• Patients in ICU are typically unable to communicate and require a specialized pain scale ^[35]
• Behavioral pain scale
  • Used to identify pain in critically ill patients on mechanical ventilation
  • Three items are evaluated and awarded points: facial expression, movement of the upper limbs, and mechanical ventilation compliance.
  • ≥ 5 points indicates significant pain
• Critical care pain observation tool (CCPOT)
  • Used to identify pain in critically ill patients.
  • Four items are evaluated and awarded points: facial expressions, body movements, ventilator compliance in intubated patients or vocalization in nonintubated patients, and muscle tension
  • ≥ 3 points indicates significant pain
• For subjective grading of pain severity by the patient, see “Pain intensity scale”

Pain management ^[36]

• Preemptive analgesia for extubation and invasive procedures
• Multimodal analgesia depending on the severity and type of pain
  • Lowest effective dose IV opioids (first-line)
  • Adjuvant NSAIDs
  • Gabapentin or carbamazepine; in case of neuropathic pain
• Consider using continuous infusions or regular doses of analgesics
• Regular assessment of the severity of pain and response to analgesia

Be aware of the adverse effects of opioids (e.g., delirium, CNS depression, tolerance) or NSAID therapy!