Pain is an unpleasant sensation (sensory and emotional) with biological, psychological, and social components. There are a number of ways to differentiate between types of pain, the most common of which is the distinction between acute and chronic pain. Acute pain lasts for < 1 month. It can indicate actual or potential tissue damage and is associated with trauma, surgery, and illness. Subacute pain lasts for 1–3 months and chronic pain is generally defined as pain lasting > 3 months (normal tissue healing time). Standardized pain intensity scales are used to evaluate pain in a clinical setting. Pain management uses a multimodal approach, which may include the use of pharmacological therapy, physical therapy, behavioral therapy, and/or interventional or surgical methods. Acute pain requires prompt treatment. Analgesics should be tailored to the inciting cause; the WHO analgesic ladder can be used to help structure pain relief strategies. The management of chronic pain can be challenging; initial management involves nonpharmacological therapy (e.g., physical therapy, cognitive behavioral therapy), nonopioid analgesia, and consideration of interventional pain management. For chronic pain refractory to nonopioid management, opioid therapy may be considered only if benefits outweigh risks. Patients who are prescribed opioid therapy for chronic pain should undergo close monitoring, and the risks versus benefits of treatment should be regularly reassessed; opioids should be tapered or discontinued if the benefits no longer outweigh the risks. For information on psychogenic pain, see “ .”
- A warning signal indicating actual or potential tissue damage that triggers a protective reaction
- Typically associated with trauma, surgery, and acute illness
- Lasts < 1 month 
- Subacute pain: lasts 1–3 months 
- Chronic pain
- 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
- For an overview of pain symptoms in patients with serious or life-threatening illnesses, see “ .”
- Pain pathway: nociceptors detect a chemical, mechanical, or thermal noxious stimulus → conversion of stimulus to an electric signal (action potential): → and 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 
Pain sensitization 
- Abnormal pain perception due to increased neuronal sensitivity to noxious stimuli () and/or reduced neuronal threshold to otherwise normal stimuli () 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., )
- Although not completely understood, the pathophysiology is thought to involve the following two mechanisms:
- 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
- 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., ) 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
- Peripheral sensitization
Subtypes and variants
- 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.
|Overview of referred pain|
|Liver, gallbladder||T10–L1||Right upper quadrant|
Phantom limb syndrome
- Phantom sensation: is a sensation that the amputated limb is still partially or totally existent
- Phantom pain: sensation of pain in an amputated limb
- Incidence: common complication after upper or lower extremity amputation
- Pathophysiology: primary somatosensory cortex neurons that formerly respond to signals from the amputated limb respond to signals from adjacent neurons that carry sensation from other parts of the body → functional reorganization of the somatosensory cortex 
- Diagnosis: diagnosed only after exclusion of other causes of stump pain (e.g., infection, ischemia, post-surgical neuroma)
- Treatment: multimodal approach
- Prophylaxis: perioperative regional anesthesia
- Pain characteristics (location, quality, temporal aspects, triggers)
- Associated symptoms (changes in mobility and strength)
- Previous pain assessments and/or treatment
- Pain intensity scale: subjective grading of pain severity by the patient
- Impact of pain
- Pain diary: regular documentation of the pain intensity to identify peaks and triggers; enables treatment optimization
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. 
WHO analgesic ladder
- Regular analgesic (modified-release drugs, administered at fixed times and doses)
- Appropriate PRN medication
- Additionally, concurrent treatment with adjuvant drugs
|Management of pain using WHO analgesic ladder |
|Step I||Mild||Include||Avoid||Avoid||If required|
|Step II||Moderate||Include||Consider||Avoid||If required|
|Step III||Severe||Include||Consider||Consider||If required|
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.
|Drug class||Drug||Important considerations|
|Nonopioids||Acetaminophen || |
|NSAIDs || |
Selective COX-2 inhibitor
All patients being discharged with opioid medications should receive .
|Drug class||Drug||Important considerations|
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. 
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 of analgesics
- Laxatives (see constipation)
- Proton-pump inhibitors (PPIs): Consider in patients taking frequent NSAIDs.
Multiple nonpharmacological therapies are often used in combination (e.g., exercise therapy and cognitive behavioral therapy).
Physical modalities 
- Thermotherapy (e.g., focused ultrasound ) 
- Desensitization techniques 
- Regular exercise (e.g. walking) and 
Psychological modalities 
Refer to a psychologist as needed.
- Relaxation techniques 
- Hypnosis 
Other modalities 
- Provide prompt analgesia for severe acute pain.
- Assess pain severity with a .
- Document recent analgesic use (e.g., type and dosage).
- Tailor the treatment strategy to the patient, the underlying condition, and the care setting.
- For specific dosages, see “Oral analgesics,” “Parenteral analgesics,” and “Adjuvant analgesics.”
|Choice of analgesic for acute pain |
|Opioids likely required||Nonopioid analgesics likely as effective as opioids|
|Surgery|| || |
|Other medical conditions|
Only prescribe opioids if the benefits outweigh the risks. 
- Risk mitigation: See “Risk mitigation for opioid prescribing.”
- Use immediate-release opioids rather than extended-release or long-acting opioids.
- Start at the lowest effective dose.
- Prescribe PRN doses rather than scheduled doses.
- Limit prescription duration to the expected duration of severe pain.
- Reevaluate the risk-benefit ratio if dosage increases are required. 
- See “Oral analgesics” and “Parenteral analgesics” for dosages.
- For management of overdose, see “Opioid overdose.”
Management of acute-on-chronic pain requires significant empathy and skill.
General principles 
Follow local departmental policies if available.
- Establish treatment goals.
- The goal of treating the acute episode is to allow the patient to return to baseline function.
- Complete alleviation of pain is typically not possible.
- Obtain detailed pain assessment and review existing care plans.
- Consult the clinical provider in charge of long-term pain management whenever possible.
- Identify and treat reversible causes of pain, e.g., a new:
- Consider systemic barriers to accessing treatment.
- Consider admission for individual management of patients with progression of terminal illnesses if no reversible cause is identified.
Acute-on-chronic pain management in hospital-based settings 
- For patients already on an opioid regimen who have uncontrolled pain:
- Individualized therapy is recommended for patients with sickle cell disease, cancer, and palliative care and/or end-of-life care needs. 
Involve the patient's regular health provider in treatment decisions whenever possible and be aware of the potential for of prescriptions made by other health providers.
- Follow analgesic.  for choice of
- For specific dosages, see “Oral analgesics,” “Parenteral analgesics,” and “Adjuvant analgesics.”
- Reassess pain severity every hour or more frequently if necessary.
- For emergency procedures, consider .
- Consider a subanesthetic ketamine infusion as a stand-alone treatment or an adjunct to opioids. 
- Extremity injuries
Minimize undertreatment 
- ED patients' pain can be undertreated for a variety of reasons, e.g., communication barriers, atypical presentations, and implicit biases.
- Patients at risk of undertreatment include children, individuals of different cultural and/or linguistic backgrounds, and individuals with neurocognitive disorders.
Ambulatory opioid prescriptions
- Limit duration to < 3–5 days.
- Arrange rapid follow-up with a regular health provider for dosage adjustments.
- See also “Opioids for acute pain.”
- Acute-on-chronic pain: See “ .”
This content applies to the management of chronic and subacute pain unrelated to cancer, sickle cell disease, or other high-morbidity illnesses. For pain related to those conditions, see “.” and are detailed separately.
- Perform an initial assessment.
- Optimize the following as needed:
- Management of 
- Condition-specific pain management
- Provide patient education on chronic pain management. 
- Consider enrolling patients into a pain management program (PMP). 
- According to the WHO analgesic ladder approach, initiate . 
- Periodically reevaluate treatment efficacy using a validated tool to assess pain and functioning (e.g, the PEG pain scale).
- For refractory pain, consider initiation of opioid therapy only if benefits outweigh risks.
Avoid perpetuating existing racial and ethnic disparities in chronic pain management. 
- Obtain a complete history and perform a physical exam, including:
- PEG pain scale  and functioning, ideally with a validated scale such as the
- Assessment of , psychosocial well-being, and other potentially contributory factors 
- Perform a medication review.
- Consider imaging and further studies as needed to: 
Refer patients with these indications to a pain management specialist: 
- Age < 18 years 
- Pregnant individuals 
- Complex regional pain syndrome
- History of
- High MME) prescription required  (
- Refractory or severe pain
- Need for interventional pain management
Individuals without indications for referral to pain management can typically be managed by a primary care clinician.
- Ensure patients understand the diagnosis and how to manage their condition; see “Managing chronic conditions.”
- Provide pain neuroscience education. 
- Manage the patient's expectations, e.g., explain that: 
- Educate patients on when to take medication for pain management.
- Support patients in developing a self-management approach. 
A combination of multimodaland various types of may be used. To select the appropriate pharmacotherapy: 
- Assess for contraindications.
- Evaluate for hepatic and/or renal impairment.
- Determine the nature of any reported adverse effects of previous therapy.
- Consider to minimize adverse effects.
- Determine the type and frequency of the pain (for dosages, see “Treatment of pain”).
- Daily pain: Consider regularly scheduled nonopioid .
- Breakthrough pain: Consider as-needed nonopioid .
- Neuropathic pain: Consider regular adjuvant analgesics (e.g., anticonvulsants, antidepressants) or topical lidocaine or capsaicin.
- Joint pain: Consider intraarticular glucocorticoid injection.
- Radiculopathy: Consider epidural glucocorticoid injection.
Decision to initiate 
- Perform a thorough evaluation of chronic noncancer pain.
- Ensure nonopioid therapy for chronic noncancer pain has been maximized and alternative treatment options have been trialed.
- Check institutional and state guidelines for indications for opioid prescribing. 
- Determine if the patient has or .
- Discuss benefits and risks of opioid therapy with patient; ensure benefits outweigh risks, given type of pain and goals of treatment. 
- If an opioid prescription is deemed appropriate, follow risk mitigation practices.
Ensure patients are aware that chronic use of opioids can interfere with employment opportunities, especially in safety-critical jobs. 
Risk mitigation 
Consider risk mitigation for opioid prescribing prior to starting opioids and at each follow-up appointment.
- Assess for the development of or .
- State and federal laws relevant to prescribing controlled substances
- The state's PDMP) (
- , if relevant
- Prescribe naloxone and provide education on its use if any of the following are present: 
- State requires coprescription
- in patient or household members
- Provide .
- Consider referral to a pain specialist and/or the use of buprenorphine for pain management in patients who: 
- Avoid concurrent use of opioids and sedative-hypnotic medications (e.g., benzodiazepines, sleeping aids; , muscle relaxants) or prescribe with extreme care.
Ensure patients with naloxone and educated on how to use it.  have been provided with
The prescription of more than a 90-day supply of opioids is associated with a dose-dependent increase in the risk of , including . 
Aberrant drug-related behaviors
- Concerning behaviors include: .
- Obtaining medication from nonmedical sources
- Requesting prescriptions early
- Frequently reporting loss of prescriptions
- Missing or canceling appointments at which no opioid refill is anticipated
- Obtaining prescriptions from multiple providers
- Presenting to the emergency department for medications
- Managing patients with aberrant drug-related behaviors
- Do not discharge patients from care unless they are violent or threatening. 
- Evaluate for and/or other ; if present, provide treatment with a multidisciplinary team.
Urine drug monitoring for opioid therapy 
- Consider urine toxicology prior to starting opioid therapy and at least annually thereafter. 
- Communicate clearly with patients to reduce misunderstandings.
- Explain urine drug monitoring procedures; and their purpose in maintaining patient safety.
- Ask nonjudgmentally about the nature and timing of all recent substance use before ordering a test.
- Interpret results with care.
- Establish the following, using shared decision-making.
- Create a and ensure has been obtained in the appropriate form. 
- Provide anticipatory guidance to avoid .
- Establish dosing and frequency based on the Treatment of pain” for specific dosages).
- Use short-acting rather than long-acting formulations.
- Start with a low dose and titrate to the lowest effective dose. 
- In patients with hepatic or renal impairment, consider longer dosing intervals.
- Prescribe as needed rather than scheduling doses. 
- Create a plan for events requiring .
- Follow-up within 1–4 weeks after initiating therapy to evaluate for improved functioning and pain control. 
Ongoing therapy 
- At least every 3 months to evaluate efficacy and safety 
- More frequently for patients with a high risk of overdose or misuse 
- Continue to:
- Maintain accurate records at every visit, including:
- Convert from immediate-release to extended-release opioids only if:
- If transitioning from one formulation to another, reduce the MME of the new formulation initially.
The decision to taper chronic opioid therapy (and, possibly, to discontinue therapy) should be made on an individual basis using , weighing up the benefits and risks of opioid therapy. 
The goal of tapering may be complete discontinuation or dose reduction to improve the risk versus benefit profile. 
Consider tapering in the following scenarios:
- Patient request
- Resolution of pain
- Lack of response to therapy, e.g.:
- Inadequate improvement in quality of life, function, or pain scores
- Escalation of dosages without improvement
- impacting quality of life
- Evidence of aberrant drug-related behaviors) or misuse (
- Overdose event or concern for impending overdose 
- Use a multidisciplinary approach.
- Avoid rapid tapering and sudden discontinuation.
- Advise patients that pain may worsen initially.
- First, reduce the dose per administration.
- Once the lowest dose per administration has been achieved:
- Gradually increase the dosing interval.
- Discontinue opioids when the interval is less than once daily.
- Follow-up monthly during tapering
- Consider the patient's wishes to slow or pause the taper.
- Evaluate for and manage complications of opioid tapering
Do not rapidly taper or discontinue opioids unless the patient is at imminent risk for life-threatening complications such as overdose. 
Inform patients that they are at increased risk for overdose during and shortly after tapering because of decreased tolerance. 
Most patients on long-term opioid therapy who agree to taper or discontinue opioids experience overall satisfaction, with improved quality of life and no increase in pain, but may experience short-term effects of hyperalgesia, insomnia, and agitation. 
Management of complications 
- Development of
- Slow or pause the taper.
- Consider .
- Inability to taper or discontinue because of ongoing pain
- Unmasking of opioid use disorder: See “Treatment of opioid use disorder.”
- Development or unmasking of depression and/or anxiety
- Overdose due to decreased tolerance: Prescribe naloxone. 
- Development of aberrant drug-related behaviors: Engage and address any underlying substance use disorders.
Special patient groups
Pain in critically ill patients
- Patients in ICU are typically unable to communicate and require a specialized pain scale 
- Behavioral pain scale
- Critical care pain observation tool (CCPOT)
- For subjective grading of pain severity by the patient, see “ ”
|Pain intensity scales for critically ill patients|
|Behavioral pain scale score||CCPOT score|
|Facial expression|| || |
|Muscle tension|| || |
|Mechanical ventilation compliance|| || |
|Vocalization for extubated patients|| || |
Pain management 
- Preemptive analgesia for extubation and invasive procedures
- Multimodal analgesia depending on the severity and type of pain
- Consider using continuous infusions or regular doses of analgesics
- Regular assessment of the severity of pain and response to analgesia
- Pain pathways are developed by the 20th week of gestation.
- Newborn and preterm infants are sensitive to pain and stress.
- Procedural pain
- 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
- Facial grimacing
- Changes in crying pattern
- 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 
- 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.
- Step 1: nonpharmacological measures, e.g., breastfeeding, use of a pacifier, skin-to-skin contact, oral sucrose
- Step 2: (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