Acute pain typically results from tissue injury such as trauma, surgery, or infection and is usually self-limited to the duration of tissue healing. Pain signals are generated in response to thermal, mechanical, or chemical stimuli and are transduced by peripheral nociceptors. These signals are transmitted via myelinated A-delta fibers and unmyelinated C fibers to the dorsal root ganglion (DRG), dorsal horn of the spinal cord and higher centers in the central nervous system ^, and are processed and modulated at various levels, including the DRG, spinal cord, and cortex, ultimately leading perception and behavioral responses.

Chronic pain is generally defined as pain lasting beyond 3 months, although there is no universally accepted clinical endpoint distinguishing acute from chronic pain. Chronic pain is now regarded as a disease entity with complex and often irreversible changes in the peripheral and central nervous systems. Chronic pain may persist even after the resolution of the initial injury and may even occur in the absence of any clear inciting event. Chronic pain affects approximately 24.3% of adults in the United States, with 8.5% experiencing pain that significantly interferes with daily life and work activities. This substantial prevalence underscores the importance of properly addressing chronic pain.

Nociception is the process of encoding noxious stimuli. Nociceptive pain results from the activation of nociceptors in response to potentially harmful stimuli. These stimuli include thermal, chemical, and mechanical inputs that lead to depolarization of nociceptor terminals via ion channels and G-protein activation resulting in the generation of action potentials. Nociceptive pain can be further classified into somatic and visceral types. Somatic pain, originating from skin, muscles, and joints, is typically sharp and well localized. Visceral pain, which arises from internal organs, is diffuse, dull, and can often be associated with autonomic symptoms.

Thermal stimuli activate ion channels such as transient receptor potential vanilloid 1 (Heat/capsaicin-sensitive pain receptor) (TRPV1) (heat) and transient receptor potential cation channel subfamily M (melastatin) member 8 (Cold/menthol-sensitive receptor) (TRPM8) (cold), while chemical and mechanical stimuli can activate acid sensing ion channels, Piezo channels, two-pore domain potassium channels (Regulate neuronal excitability and pain signaling) (K2P) channels, and transient receptor potential ankyrin 1 (Irritant-sensitive receptor involved in inflammatory pain) (TRPA1). These channels allow the influx of cations, initiating depolarization. The subsequent action potential is propagated via voltage-gated sodium channels, notably Nav1.7, Nav1.8, and Nav1.9 via A-delta and C fibers, to the rexed laminae of the dorsal horn of the spinal cord. Pain signals are then relayed via projection neurons, including wide dynamic range neurons, to higher centers such as the thalamus and somatosensory cortex.

Inflammatory mediators, such as prostaglandins and cytokines, can sensitize nociceptors and upregulate sodium channels like Nav1.7, amplifying pain signaling. Optogenetic studies have further demonstrated how specific neuronal populations can be activated or silenced directly, elucidating the pathways involved in nociception.

Neuropathic pain arises from damage or disease affecting the somatosensory system. It may originate from central structures (eg, spinal cord injury and stroke) or peripheral nerves (eg, diabetic neuropathy and postherpetic neuralgia). It is often described as burning, pricking, electric-shock-like, paresthesia, or shooting in quality. ^, Neuropathic pain mechanisms are diverse, and often involve partial rather than complete nerve damage, leading to hyperexcitability and spontaneous activity in affected neurons. Mechanisms such as ectopic discharges from injured neurons, sensitization of central pain pathways, loss of inhibitory interneurons, and neuroinflammatory responses, including the activation of microglia and astrocytes, have all been proposed.

Neuropathic pain accounts for 15% to 25% of chronic pain cases and can arise from vascular, metabolic, traumatic, autoimmune, infectious, or genetic conditions with the most common etiologies including diabetic neuropathy, postherpetic neuralgia, and radiculopathy. Despite its prevalence, there are no definitive biomarkers, and diagnosis often relies on clinical assessment and symptom descriptors.

The term nociplastic pain was first introduced in 2016 to describe pain arising from altered nociceptive processing without clear evidence of actual or threatened tissue damage or somatosensory system pathology. It encompasses conditions such as fibromyalgia, interstitial cystitis, irritable bowel syndrome, chronic low back pain, and tension-type headache. In 2019, the International Statistical Classification of Diseases recognized primary pain syndromes such as those listed earlier, where pain itself is the primary disease rather than a symptom of another condition.

Nociplastic pain typically presents with widespread, poorly localized pain described as dull, aching, or deep. Dysesthesia, paresthesia, and symptoms such as fatigue, cognitive dysfunction, and mood disturbances are common.

Cultural norms and beliefs strongly influence how individuals perceive, express, and cope with pain. In cultures that value stoicism, such as certain East Asian or Northern European traditions, individuals may underreport pain or avoid visible expressions of discomfort. In contrast, other cultures may encourage verbal and nonverbal expressions, such as vocalizations or gestures, as a means of communicating distress. Preferences for pain-related social interactions also vary; some individuals desire solitude during painful experiences, while others prefer attentive support.

Religious and spiritual beliefs are also influential. Some faith traditions frame pain as redemptive or divinely purposed, potentially altering the emotional and behavioral response to it. ^, These deeply held cultural frameworks must be considered when assessing pain in diverse populations to avoid misinterpretation of underreporting or overreporting.

Emotional state is a powerful modulator of pain perception. Numerous studies have shown that depression, anxiety, posttraumatic stress disorder, and catastrophizing are associated with lower pain thresholds and higher pain-related disability. Prevalence of pain among individuals with comorbid depression ranges from 15% to 100%, with a mean of 65%. These findings underscore the need to assess emotional health when evaluating pain.

Psychological trauma, especially early in life, has been strongly linked to chronic pain development. Conversely, focused attention or distraction can significantly diminish pain perception. For example, soldiers in combat may not perceive pain from severe injuries due to intense cognitive focus on survival.

Biological factors such as age, sex, and hormonal status are also crucial in pain assessment. Women tend to report greater pain intensity and show different analgesic responses compared to men, due in part to estrogen’s effect on nociceptive signaling pathways. ^, These differences are further reflected in pediatric populations; in one study, girls developed complex regional pain syndrome (CRPS) earlier and experienced longer recovery times compared to boys.

In elderly patients, physiologic and cognitive changes complicate pain evaluation and management. Aging is associated with diminished A-delta fiber transmission and altered central pain processing, potentially masking nociceptive input. Metabolic changes—such as reduced hepatic blood flow and glomerular filtration rate—alter pharmacokinetics and pharmacodynamics. Additionally, comorbid medical conditions like diabetes and autoimmune disorders can directly influence pain processing through mechanisms like peripheral neuropathy or systemic inflammation.

A thorough pain-focused examination—inspection, palpation, range of motion (ROM), neurologic evaluation, and special tests are key for diagnosis.

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  Inspection: Include visual observation for swelling, skin changes, muscle atrophy, joint deformity, and posture abnormalities.

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  Palpation: Identify tenderness, trigger points, muscle tightness, joint effusion, or abnormal tissue textures.

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  ROM: Move the joint to identify limitations or pain and compare both sides for symmetry.

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  Provocative maneuvers: Reproduce the pain by applying pressure or movement in a certain way. The sensitivity and specificity of examination maneuvers is limited but can provide insight into potential sources of pain. Common tests include

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    Spurling’s test suggests cervical radiculopathy.

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    Straight leg raising (SLR) and crossed SLR tests suggest lumbar radiculopathy.

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    Flexion, abduction, and external rotation (test) (Physical exam maneuver used to assess hip or sacroiliac joint pathology) (FABER) test can assist in diagnosis of hip or sacroiliac joint pathology.

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    Hoffmann’s test helps to evaluate upper motor neuron dysfunction and central nervous system involvement.

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    Neurologic examination: checking for sensory, muscle strength, and reflexes in the affected area to assess neuropathic pain and potential nerve involvement.

It is essential when visceral or referred pain is suspected, as cardiac, respiratory, abdominal, or renal conditions can mimic musculoskeletal pain.

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  Cardiac: shoulder/back pain may indicate heart issues; assess with auscultation and electrocardiogram.

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  Respiratory: pleuritic pain radiating to the back/shoulders; check lung sounds.

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  Abdominal: ulcers, pancreatitis, or gallbladder issues can cause mid-back pain; evaluate via palpation and regions of tenderness (McBurney’s point, Rovsing’s sign, Psoas sign, and so forth).

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  Renal: stones or infections may refer pain to the flank/lower back; check for costovertebral angle tenderness.

A questionnaire or scale for patients to describe and rate their pain; widely used in clinical and research settings.

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  Unidimensional pain scales : Measure only pain intensity—simple and quick but exclude pain quality and functional impact.

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    VAS: A 10 cm horizontal or vertical line where patients mark their pain intensity, ranging from “no pain” to “worst pain imaginable.”

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    Numerical Rating Scale: Patients rate their pain on a 0 to 10 or 0 to 100 scale, with higher numbers indicating greater pain severity.

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    Verbal Rating Scale: Uses descriptive terms (eg, “no pain,” “mild pain,” “moderate pain,” “severe pain”) to quantify pain intensity.

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  Multidimensional Pain Scales

• Assess pain intensity plus sensory, emotional, and functional aspects; often used for chronic pain (eg, neuropathic, cancer, and musculoskeletal). ^,

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    McGill Pain Questionnaire: A detailed questionnaire that evaluates pain quality using sensory, affective, and evaluative descriptors.

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    Brief Pain Inventory (BPI): It assesses pain severity and its impact on daily activities.

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    Patient Specific Functional Scale (PSFS): It assesses pain-related functional impairment. This is a valid and reliable scale using which each patient lists activities they feel they are unable to do or have difficulty with, along with their corresponding levels of limitation (0 “unable to perform activity” to 10 “able to perform activity at same level as before injury or problem”) in these activities.

For nonverbal patients (eg, infants and cognitively impaired), assess pain via facial expressions, body movements, and physiologic signs.

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  FLACC Scale (Face, Legs, Activity, Cry, Consolability)

For infants and nonverbal patients, scores based on facial expression, leg movements/tone, body activities, crying, ease of consolability.

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  PAINAD (Pain Assessment in Advanced Dementia Scale)

For patients with dementia, evaluate breathing, vocalization, facial expressions, body language, and consolability.

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  Behavioral Pain Scale:

Used in sedated or nonverbal patients; assesses facial expression, upper limb movements, and ventilation compliance.

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  Pediatric pain assessment

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    Wong-Baker Faces Pain Rating Scale: It uses 0 to 5 scales with facial expressions from smiling to crying to show pain intensity.

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    The Face Pain Scale-Revised: It uses 0 to 10 self-report scale for children, showing neutral to painful facial expressions.

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    Children’s Hospital of Eastern Ontario Pain Scale: It evaluates postoperative pain by assessing crying, facial expressions, and movement in young children.

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  Pain assessment in older adults

• Pain is often underreported, especially in those with dementia. Tools for this population include

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    Abbey Pain Scale: It observes vocalization, facial expression, body language, and physiologic changes in patients with dementia.

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    PAINAD: Adapted behavioral tools for advanced dementia, also effective in older adults.

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  Military Service Members and Veterans

Pain intensity and activity interference in military personnel: Defense and Veterans Pain Rating Scale, Pain Assessment Screening Tool and Outcomes Registry, and Defense & Veterans Center for Integrative Pain Management resources.

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  Neuropathic pain assessment

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    Douleur Neuropathique 4: A 10 item tool for neuropathic pain, including 7 symptoms (eg, burning, tingling, and electric shocks) and 3 examination findings (eg, hypoesthesia and allodynia).

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    PainDETECT: A 9 item self-report tool for assessing neuropathic pain, including 7 sensory symptoms (0–5 scale), 1 pain pattern (−1 to +1), and 1 pain radiation (0—no radiation, +2—radiating pain).

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    Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale: It combines symptom self-report and sensory testing. Score of 12 or greater indicates likely neuropathic pain.

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  Nociplastic pain (central sensitization)

• Chronic pain from altered central nociception, but not direct tissue damage. Assessment includes pain hypersensitivity, widespread pain, fatigue, and sleep disturbance.

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    Central Sensitization Inventory: A 25 item self-report tool for central pain amplification (eg, fibromyalgia and headaches); higher scores = greater sensitization.

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    Fibromyalgia Impact Questionnaire (FIQ): A self-report tool measuring fibromyalgia’s impact on pain, function, fatigue, and mood.

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  Chronic pain assessment

• Functional disability is a major concern in chronic pain.

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    Oswestry Disability Index: A self-administered questionnaire assessing low back pain–related disability (eg, back pain, personal care, and mobility). Higher scores indicate greater disability.

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    FIQ: As mentioned earlier, it assesses fibromyalgia-related chronic pain.

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  Autonomically mediated pain assessment

Pain involving autonomic dysfunction requires specialized testing.

Quantitative sensory testing: It assesses thermal, vibration, and pressure pain thresholds; useful for neuropathic pain.

Heart rate variability (HRV) analysis: It assesses autonomic balance via heartbeat interval changes; used for stress, cardiovascular, and autonomic function.

Sympathetically mediated pain (SMP) testing: It identifies pain driven by sympathetic activity, often using sympathetic blocks.