Pain Physiology

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Nociception & Transduction - Ouch! It Starts Here

  • Nociception: Neural encoding of noxious stimuli.
  • Nociceptors: Free nerve endings detecting intense mechanical, thermal (>45°C, <5°C), or chemical stimuli.
    • Types: Mechanical, Thermal, Chemical, Polymodal, Silent (inflammation-activated).
    • Chemicals: Bradykinin, Prostaglandins, Histamine, Serotonin, H+, K+, ATP.
  • Transduction: Noxious stimuli → action potentials via ion channels.
    • Key channels:
      • TRPV1 (heat >43°C, capsaicin, H+).
      • TRPM8 (cold, menthol).
      • TRPA1 (irritants, cold).
      • ASICs (acid).
      • Nav1.7 (Na+ channel).
  • Peripheral Sensitization: ↑ Nociceptor responsiveness at injury.
    • Mediators: Prostaglandins (PGs), Bradykinin.
    • Results in hyperalgesia, allodynia. Nociceptor transduction and ion channels

⭐ TRPV1 receptor is activated by capsaicin, heat >43°C, and H+ ions (protons).

Pain Pathways - The Neural Superhighway

Pain signals ascend via a three-neuron chain:

  • 1st Order Neuron (Primary Afferent):
    • Cell body: DRG (body); Trigeminal Ganglion (face).
    • Fibers: (fast, sharp, localized, myelinated); C (slow, dull, diffuse, unmyelinated).
    • Synapse: Dorsal horn (Rexed laminae I, II, V). NTs: Glutamate, Substance P.
  • 2nd Order Neuron:
    • Location: Dorsal horn.
    • Decussates: Anterior white commissure.
    • Ascends in anterolateral system:
      • Spinothalamic tract (STT): To thalamus (pain, temp).
      • Spinoreticular tract: To reticular formation (arousal).
      • Spinomesencephalic tract: To PAG (modulation).
  • 3rd Order Neuron:
    • Location: Thalamus (VPL-body, VPM-face). 📌 VPL for Lateral body/Legs; VPM for Medial face/Mouth.
    • Projects: Somatosensory cortex (S1, S2 - perception/localization); Limbic system (insula, cingulate - emotion).

⭐ The Spinothalamic tract is the principal pathway for transmitting nociceptive information to higher brain centers.

Pain Modulation - Turning Down the Volume

  • Descending Inhibitory Pathways: Brain's natural analgesia.
    • Origin: Periaqueductal Gray (PAG), Rostral Ventromedial Medulla (RVM) including Nucleus Raphe Magnus (NRM), Locus Coeruleus (LC).
    • Neurotransmitters: Serotonin (5-HT from NRM), Norepinephrine (NE from LC), Enkephalins.
    • Action: Inhibit nociceptive transmission in dorsal horn (Substantia Gelatinosa).
  • Gate Control Theory (Melzack & Wall):
    • Aβ fibers (touch) activate inhibitory interneurons in SG.
    • "Closes gate" to Aδ/C fiber pain signals.
    • Basis for TENS. 📌 Rubbing hurts less!
  • Endogenous Opioids: (Enkephalins, Endorphins, Dynorphins)
    • Act on μ, δ, κ receptors.
    • Mechanism: ↓ $Ca^{2+}$ influx (pre-synaptic), ↑ $K^{+}$ efflux & hyperpolarization (post-synaptic).

⭐ Descending pathways primarily utilize serotonin and norepinephrine to inhibit pain signals at the spinal cord dorsal horn.

Descending Pain Modulation Pathway and Neurotransmitters

  • Nociceptive Pain: Normal response to tissue injury.
    • Somatic: Sharp, localized (skin, muscle, bone). E.g., fracture, burn.
    • Visceral: Dull, poorly localized, referred (organs). E.g., appendicitis, MI.
  • Neuropathic Pain: Nerve damage/dysfunction (PNS/CNS).
    • Burning, tingling, shooting, "pins & needles".
    • E.g., diabetic neuropathy, post-herpetic neuralgia.
    • Features: Allodynia, hyperalgesia.
  • Nociplastic Pain (Central Sensitization): Altered pain processing; no clear injury/neuropathy.
    • Widespread pain, fatigue. E.g., fibromyalgia, IBS.
  • Referred Pain: Pain felt distant from origin.
    • Mechanism: Afferents converge on same spinal segment.

    ⭐ Kehr's sign: Spleen rupture (phrenic nerve C3-C5 irritation) causes left shoulder tip pain.

High‑Yield Points - ⚡ Biggest Takeaways

  • Aδ fibers: fast, sharp pain (first pain); C fibers: slow, dull pain (second pain).
  • Spinothalamic tract: primary ascending pathway for pain & temperature.
  • Gate control theory: pain modulation in substantia gelatinosa of spinal cord.
  • Endogenous opioids (endorphins, enkephalins) are natural analgesics.
  • Referred pain: visceral pain felt at a distant somatic site.
  • Neuropathic pain: due to nerve damage; often chronic and burning.
  • Allodynia: pain from non-painful stimuli; Hyperalgesia: increased pain sensitivity.

Practice Questions: Pain Physiology

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Slow, burning pain is primarily carried by which type of nerve fibers?

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Flashcards: Pain Physiology

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_____ theory assumes three sets of receptor systems, each of which functions as an antagonistic pair

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_____ theory assumes three sets of receptor systems, each of which functions as an antagonistic pair

Opponent process

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