Summary
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 non-opioids 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.
Types of pain
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
Types of pain [2]
- Nociceptive pain: pain that is triggered by chemical, mechanical, or thermal stimuli (noxious stimuli)
-
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 signficant driver to the sensitization of central nociceptive neurons
- Usually continues even after the initial injury has healed
-
Peripheral sensitization
Referred pain
- 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's sign: left shoulder pain associated with diaphragmatic irritation due to splenic rupture
- Left-sided chest and arm pain: myocardial infarction
- Periumbilical pain in early stages of appendicitis
- Treatment: Select treatments may reverse this pathway
| Overview of referred pain | ||
|---|---|---|
| Organ | Dermatome | Projection |
| Diaphragm | C4 | Shoulders |
| Heart | T3–4 | Left chest |
| Esophagus | T4–5 | Retrosternal |
| Stomach | T6–9 | Epigastrium |
| Liver, gallbladder | T10–L1 | Right upper quadrant |
| Small bowel | T10–L1 | Periumbilical |
| Colon | T11–L1 | Lower abdomen |
| Bladder | T11–L1 | Suprapubic |
| Kidneys, testicles | T10–L1 | Groin |
Referencs:[6][7][7][8]
Phantom limb syndrome
-
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
- Prophylaxis: perioperative regional anesthesia
References:[9]
Evaluation of pain
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 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:[10]
Treatment of pain
WHO analgesic ladder
The WHO analgesic ladder is a 3-step algorithm for the management of acute and chronic pain.
-
Principles
-
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-orientated): 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 ≥ 3x/d → inadequate analgesia likely; review the regular medication
- Additionally, concurrent treatment with adjuvant drugs
-
Regular analgesic (modified-release drugs, administered at fixed times and doses)
| Pain severity | Non-opioid analgesics | Mild opioids | Strong opioids | Adjuvant drugs | |
|---|---|---|---|---|---|
| Step I | Mild pain | ✓ | - | - | If required |
| Step II | Moderate pain | ✓ | ✓ | - | If required |
| Step III | Severe pain | ✓ | - | ✓ | If required |
Nonopioid analgesics are first-line agents for mild to moderate pain [11]
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
| Oral analgesics | |||
|---|---|---|---|
| Drug class | Drug | Important considerations | |
| Nonopioids | Acetaminophen [12] |
| |
| NSAIDs [12] |
| ||
| Selective COX-2 inhibitor |
| ||
| Opioids |
| ||
| Combination analgesics |
| ||
Parenteral analgesics
| Parenteral analgesics | ||
|---|---|---|
| Drug class | Drug | Important considerations |
| NSAIDs |
| |
| Opioids |
|
|
Analgesic suppositories
Topical analgesics
| Topical analgesics | ||
|---|---|---|
| Drug | Dose | Indications |
| Lidocaine |
| |
| Diclofenac |
|
|
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.
Muscle relaxants
Consider muscle relaxants in patients with pain associated with muscle spasticity.
- Cyclobenzaprine
- Methocarbamol
- Baclofen
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. [23][24]
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.
Additional methods for pain management
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
- Relaxation techniques
References:[26][27]
Pain in neonates and infants
-
Background [28]
- Pain pathways are developed by the 20th 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 [28][29]
- 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
- Principles
Pain in critically ill patients
Assessment of pain in the ICU
- Patients in ICU are typically unable to communicate and require a specialized pain scale [30]
-
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)
- For subjective grading of pain severity by the patient, see “Pain intensity scale”
| Pain intensity scales for critically ill patients | ||
|---|---|---|
| Behavioral pain scale score | CCPOT score | |
| Facial expression |
|
|
| Movement |
| |
| Muscle tension |
|
|
| Mechanical ventilation compliance |
|
|
| Vocalization for extubated patients |
|
|
Pain Management [31]
- 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!