pain (25-26) Flashcards
(16 cards)
What are the main components of the pain pathway from stimulus to perception?
Nociceptors detect thermal, mechanical, and chemical stimuli.
Primary sensory neurons in the dorsal root ganglion transmit signals via Aδ and C fibers.
Spinal cord (dorsal horn) processes the signal using glutamate and neuropeptides.
Ascending pathways relay signals to the brain (thalamus → cortex for localization, limbic system for emotion).
Descending pathways from the PAG and RVM modulate pain via 5-HT and NA.
What are the roles of Aδ and C fibers in pain?
Aδ: Fast, sharp, localized pain (thinly myelinated).
C fibers: Slow, dull, burning pain (unmyelinated).
How do descending pain pathways modulate pain?
They regulate pain through the PAG and RVM using serotonin and noradrenaline, either amplifying or suppressing spinal nociceptive transmission.
What is peripheral sensitization and how does it contribute to chronic pain?
It’s a reduced threshold for nociceptor activation due to inflammatory mediators, leading to increased pain responses (hyperalgesia).
What is central sensitization?
Heightened excitability in the spinal cord and brain after injury, reducing inhibition and enhancing pain signals. Leads to allodynia and spontaneous pain.
Give examples of chronic pain conditions and associated mechanisms.
Arthritis: Inflammatory pain, peripheral/central sensitization.
Diabetic neuropathy: Neuropathic pain from nerve damage.
Post-surgical pain: Nerve injury leads to maladaptive pain signaling.
What are key biological risk factors for developing chronic pain?
Persistent inflammation
Nerve injury
Overexpression of pain-related ion channels
Central nervous system dysfunction
What psychosocial factors increase chronic pain risk?
Negative expectations (nocebo effect)
Depression, anxiety
Poor coping mechanisms
Social isolation
What role does neuroplasticity play in chronic pain?
It underlies the long-term changes in neuron excitability and connectivity, keeping pain circuits active even after healing.
How do opioids relieve pain?
Bind to opioid receptors in CNS and PNS.
Inhibit glutamate and neuropeptide release (presynaptic) and hyperpolarize neurons (postsynaptic).
Also enhance descending inhibitory pathways.
What is the mechanism of NSAIDs?
Inhibit COX-1/COX-2 enzymes → ↓ prostaglandin E2 → ↓ nociceptor sensitization in both CNS and PNS.
How do antidepressants (TCAs/SNRIs) treat pain?
Increase serotonin and noradrenaline levels in descending pain pathways.
Restore inhibitory tone, reducing central sensitization.
How do anticonvulsants like pregabalin work?
Bind to α2δ subunit of Ca²⁺ channels → reduce neurotransmitter release → ↓ spinal excitability and central sensitization.
What are limitations of current analgesics?
Side effects (GI, addiction, sedation)
Not pain-specific (e.g., antidepressants repurposed)
Varying effectiveness across individuals
Why do many pain treatments fail in clinical trials?
Animal models don’t reflect human disease mechanisms.
Lab assessments use reflexes; clinics rely on subjective reports.
Sex bias in research (most animals are male).
Human pain is influenced by psychological and contextual factors.
What are current efforts to improve translational pain research?
Use disease-relevant models (e.g., cancer pain, diabetes).
Include both sexes.
Develop biomarkers and better clinical assessments.
Personalize treatments based on pain mechanism.
