Nervous System IV

pain

an unpleasant sensory and emotional experience associated with actual or potential tissue damage

-perception of signal

nociception

propagation (transmission) of pain signal

durations of pain

-acute <1 month

-subchronic 1-3 months

-chronic >3 months

causes of pain

nociceptive, neuropathic, nociplastic, mixed

nociceptive

tissue injury/inflammation

nociception pathway

noxious stimulus → transduction → transmission → modulation → perception

nociceptors

high-threshold sensory nerve endings that respond to potentially damaging stimuli

-mechanical (pinch, cut, pressure)

-thermal (heat/cold)

-chemical (inflammation, H⁺, mediators)

transduction

turning tissue threat into an electrical signal

sensory fibers

different axons carry different sensory info

-three types: A_ß, A_σ, C

A_ß sensory fiber

touch/pressure, non-nociceptive, large myelinated

A_σ sensory fiber

sharp/pricking, fast pain, thinly myelinated

C sensory fiber

dull/burning/aching, slow pain, unmyelinated

how pain signals travel to brain

first order neuron enters dorsal horn → synapses → second order neuron crosses to opposite sides → ascends in anterolateral/spinothalamic pathway → thalamus → corticol targets

somatosensory cortex

location & intensity of pain

insula/cingulate

affective & salience components of pain

prefrontal cortex

attention & appraisal of pain

thalamus

relay & integration of pain

how brain understands pain signals

-modality (which receptor/pathway is activated)

-location (which line enters the CNS)

-intension (how often are neurons firing, how many fibers recruited)

-duration

modulation of pain

pain signals can be increased or decreased before reaching conscious

ascending pathways

transmit nociceptive information to brain

descending pathways

modulate nociceptive processing in dorsal horn

gate control theory

A_ß touch input can recruit inhibitory interneurons, reducing A_σ/C nociceptive output (reducing pain)

endogenous opioid peptides

help regulate nociceptive signaling (endorphins, enkephalins, dynorphins)

endorphins

participate in pain modulation

-CNS & stress responses

enkephalins

reduce nociceptive transmission

-spinal cord pain circuits

dynorphins

pain modulation

-spinal mechanisms

opioid receptors

inhibitory GPCRs (µ, κ, δ)

-metabotropic

µ opioid receptor

major receptor in analgesia

κ opioid receptor

contributes to endogenous pain modulation

σ opioid receptor

endogenous pain modulation

opioid mechanism at dorsal horn

opioid receptor activation reduces transmitter release (less Ca²⁺) & postsynaptic excitability (more K⁺) → reduced pain

peripheral sensitization

tissue injury → release of chemicals, stimulate nociceptors → vasodilation, swelling, histamines → lower pain threshold (increased nociceptor responsiveness)

-primary hyperalgesia at injured site

central sensitization

persistent/repeated nociceptive input increases responsiveness of CNS neurons

-hyperalgesia and allodynia

hyperalgesia

amplification of pain (ex. needle stick in inflamed skin)

allodynia

pain from stimuli normally not painful (ex. sunburn)

visceral pain

from internal organs

-diffused, poorly localized

-associated with some autonomic symptoms (nausea, sweat)

referred pain

pain at site different from injured organ

neuropathic pain

caused by lesion or disease of somatosensory nervous system (nerve damage)

-abnormal nerve firing → pain, increased responsiveness

nociplastic pain

from altered nociceptive processing; no clear ongoing tissue injury or nerve lesion to explain pain (ex. IBS)

neuralgia (peripheral)

pain felt along distribution of sensory nerve

-burning, electric, shooting, stabbing

-spontaneously or by touch (injury, irritation, disease)

NSAIDs

act in peripheral; lower COX and prostaglandins

gabapentenoids

act in dorsal horn synapse; lower excitatory transmission

antidepressants

act in descending pathways; enhance monoamine mediated inhibatory

opioids

act in spinal & supraspinal sites; µ-receptor activation