What is Pain?

  • The International Association for the Study of Pain (IASP) definition: "an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage."
    • An evolutionary response to perceived or actual danger that serves as the body’s warning system
    • Pain is complex, subjective, and constructed by both brain and body working in concert
    • Can be a symptom of an underlying issue or condition, or a health problem in its own right 
    • Pain and nociception are not the same, and pain is not an accurate indicator of tissue damage. Pain can occur in the absence of damage, and physical damage can occur in the absence of pain (see: How Pain Works)
    • Pain can be expressed verbally and/or nonverbally


  • Pain is a diffuse neurological process informed by both PNS and CNS. CNS pain processing sites include somatosensory cortex, motor cortex, prefrontal cortex, insular cortex, anterior cingulate cortex, amygdala, hippocampus, thalamus, basal ganglia, brain stem, midbrain, spinal cord 
  • Critical role of limbic system reveals that pain is never purely physical, but is also always emotional 
  • All pain is biopsychosocial. Three domains interact to produce and reduce acute and chronic pain: 
    • Biological: age, genetics, tissue damage, system dysfunction, anatomical and biomechanical issues, inflammation, diet, sleep, etc. 
    • Psychological: thoughts, beliefs, memories, appraisals and evaluative processes, executive and attentional processes, emotions (stress, anxiety, depression, anger, etc), trauma, coping behaviors, etc. 
    • Social / Sociological: socioeconomic status, access to care, race, culture, ethnicity, family factors, home environment, media, society, context, environmental factors, etc
  • Effective treatment requires a multidisciplinary approach targeting brain and body, combining medicine, psychology, physical therapy, occupational therapy, biofeedback, and other modalities. 
  • Biomedical and psychosocial interventions must be prioritized equally.
  • CNS is highly plastic and therefore easily altered by physiological, pharmacological, emotional, cognitive and environmental inputs.


Acute vs. Chronic Pain

Acute and chronic pain can be experienced anywhere in the body. Differ based on length and treatment approach:

  • Acute pain: pain lasting ≤ 3 months 
    • e.g., broken bone, second-degree burn, pain of childbirth, post-surgical pain
    • Treatment: rest + appropriate care (pharm + nonpharm)
  • Chronic pain (CP): pain lasting ≥ 3 months or beyond expected healing time
    • CP can be linked to specific conditions like migraine, fibromyalgia, sickle cell disease, cancer – or may become a condition in its own right
    • Occurs when pathologic changes in nervous, immune and inflammatory systems create a state of hypersensitivity and over-activation in which signals from the body are amplified and exaggerated, even when the body isn’t in danger 
    • There is documented, altered CNS structure and function in CP patients
    • Neurons that fire, wire: Central sensitization is one of the processes by which the brain learns pain via continued use of “pain pathways” over time. This sensitivity results in amplification and possible misinterpretation of benign sensory signals.
    • CP can be maladaptive and destructive, resulting in significant impairment across domains: employment, social relationships, emotional functioning, physical activity, hobbies, sexual functioning, ADLs. May result in kinesiophobia.  
    • CP can both lead to and be triggered by trauma, depression, anxiety, toxic stress (e.g. ACES studies) 
    • CP is exacerbated by extended periods of rest, inactivity, and social withdrawal.
    • Treatment: Requires a multidisciplinary team to target all biopsychosocial factors. Plans that include only biomedical interventions (medications, procedures) are incomplete. All tx plans should include psychosocial + nonpharmacological interventions. 
    • Opioids sensitize the brain to pain over time and are therefore never indicated for CP (pain > 3 months or pain beyond expected healing time). Exceptions to this are rare and only if the benefits are greater than the risks under the management of an expert in multidisciplinary pain medicine.
    • Nonpharmacological, biobehavioral interventions with evidence of effectiveness include Cognitive Behavioral Therapy (CBT), biofeedback, Mindfulness-Based Stress Reduction (MBSR), etc (see Nonpharmacological Pain Management)


How Pain Works

Pain and nociception are different phenomena: nociception does not require conscious recognition of pain. Pain therefore cannot be inferred solely from activity in sensory neurons. 


  • Nociceptors (e.g. thermoreceptors, mechanoreceptors and chemoreceptors) in the periphery detect potentially dangerous changes in temperature, pressure, and chemicals
  • Send information up spinal cord 
  • Motor neurons then initiate movements that quickly change behavior to protect the body (e.g., pulling hand off hot stove)
  • Nearly all animals, even those with simple nervous systems, experience nociception
  • Signals do not need to reach higher brain centers for nociception to occur


  • Sensory information from the body + nociceptors travel from spinal cord up to brain 
  • Conscious recognition of potential danger occurs 
  • Sensory signals are modulated by cognitive, emotional and contextual inputs
  • Brain incorporates input from nociceptors, five senses, thoughts, memories, emotions, environment, and other biopsychosocial inputs to determine whether or not to make pain, and how much.  
  • Multiple CNS sites work together to reach a conclusion about what’s happening and how to respond: somatosensory cortex, motor cortex, prefrontal cortex, insular cortex, anterior cingulate cortex, amygdala, hippocampus, thalamus, basal ganglia, brain stem, midbrain, and others
  • If there’s any reason to believe protection is required, the brain will make pain.
  • Brain then sends messages back down to body via spinal cord, informing subsequent decisions and actions
  • Valence matters: Negative thoughts and emotions (e.g. anxiety, stress, sadness, anger) amplify pain. Positive thoughts and emotions (e.g. happiness, gratitude, relaxation) attenuate it.
  • Context matters: injuries sustained in negative or stressful circumstances feel worse than those that occur in relaxing, positive contexts. Pleasurable situations and distractions attenuate pain, while attending to and worrying about pain amplifies it. The same sensory input in one context may be benign or pleasurable (e.g., a playful kick) and painful in another (e.g., the same kick sustained during a fight)
  • Pain is a guesstimate, the brain’s best guess based on all available information. Pain is not an accurate indicator of whether the body is actually damaged, nor how much.



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