Structure and Function of Nociception

• Ascending pathway of pain

  1. Pain signal from injury travels up to the brain

  2. Signal goes to somatosensory cortex

  3. Somatosensory cortex has areas for different body parts

  4. Signal goes from spinal cord to thalamus

  5. Thalamus relays signal to somatosensory cortex
• Somatosensory cortex


  • Area where sensation, including pain, is perceived
  • Has areas that correlate to different parts of the body
• Spinal cord

  • Contains nerves coming in from posterior root (sensory)
  • Contains spinal thalamic tract (pain pathway)
• Ascending pathway of pain


  1. Damaged cells release prostaglandins

  2. Prostaglandins stimulate sensory nerve fibers

  3. Sensory nerve fibers carry signal to dorsal horn of spinal cord

  4. First order neuron synapses with second order neuron

  5. Second order neuron crosses over and enters spinal thalamic tract

  6. Second order neuron ascends to thalamus

  7. Third order neuron carries signal to somatosensory cortex
• Substance P

  Chemical released by first order neuron to transmit signal to second order neuron
• Descending pathway of pain


  1. Periaqueductal gray matter of midbrain sends neurons to nucleus raphe magnus

  2. Nucleus raphe magnus sends serotonergic/noradrenergic neurons to dorsal horn of spinal cord

  3. These neurons inhibit release of substance P and activation of second order neuron
• Substantia gelatinosa

  • Area in dorsal horn of spinal cord that is important for pain pathway
  • Contains interneurons that release endogenous opioids (e.g. enkephalin)
  • Endogenous opioids inhibit release of substance P and activation of second order neuron
• Opioids inhibit the ascending pathway of pain
• Nociceptors


  Pain sensing nerve cells in the periphery (skin, joints, muscles)
• Pain sensation

  1. Noxious stimuli (e.g. nail penetrating skin)

  2. Nociceptors stimulated

  3. Nociceptors release pain neurotransmitters

  4. Second order neuron receives information

  5. Second order neuron crosses over to opposite side of spinal cord

  6. Second order neuron transmits information to brain via spinothalamic tract
• Types of nociceptors

  • Alpha delta fibers (fast, well-localized sharp pain)
  • C fibers (slow, poorly-localized burning/throbbing pain)
• Spinothalamic tract


  Pathway in spinal cord that transmits pain information to thalamus in brain
• Thalamus


  Relay station in brain that receives pain information from spinal cord
• Somatosensory cortex


  Area of brain's cortex that processes sensations like touch and pain, with specific regions corresponding to different body parts
• Homunculus


  Distorted human figure representation of the somatosensory cortex, showing the relative sensitivity of different body parts
• Pain location

  Processed in opposite side of brain from where pain originated
• Ascending pain pathway

  Nociceptors to spinal cord to thalamus to somatosensory cortex
• There is also a descending pain regulatory pathway that modulates the ascending pathway, but this was not covered in the video
• Nociception

  The neural process of encoding and processing noxious stimuli
• Pain: An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage

  
• Pain is always a personal experience that is influenced to varying degrees by biological, psychological, and social factors

  
• Pain and nociception are different phenomena. Pain cannot be inferred solely from activity in sensory neurons

  
• Although pain usually serves an adaptive role, it may have adverse effects on function and social and psychological well-being
• Types of pain by source

  • Cutaneous (e.g. paper cut)
  • Deep somatic (ankle sprain)
  • Visceral (GI distress)
  • Autonomic responses (N/V, diaphoresis, pallor)

  
• Referred pain


  Pain that is felt in a location other than the site of the painful stimulus

  
• Guarding


  Protective muscle contraction in response to pain
• Acute vs chronic pain

  Acute pain is <6 months, chronic pain is ~>6 months but can vary
• Autonomic responses are associated with acute pain, while chronic pain can negatively impact quality of life
• Specificity theory of pain


  Pain has a separate sensory modality from other senses

  
• Pattern theory of pain


  Pain shares endings/pathways with other sensory modalities, e.g. light touch vs intense pressure

  
• Gate control theory of pain


  Modification of specificity theory, with "gating" at the spinal cord level to regulate transmission of impulses to the CNS

  
• (small) A-delta and C fibers "open" the pain gate, while (large) A-beta fibers "close" the gate
• Components of a typical cutaneous nerve


  • Primary afferents with cell bodies in the dorsal root ganglion
  • Sympathetic postganglionic fibers with cell bodies in the sympathetic ganglion

  
• Primary afferent axon types

  • Large-diameter myelinated (Aβ)
  • Small-diameter myelinated (Aδ)
  • Unmyelinated (C)
• Mechanisms of pain

  • Nociceptive
  • Transduction
  • Conduction
  • Transmission
  • Perception
  • Modulation

  
• Nociceptive


  Relating to the neural processes of encoding and processing noxious stimuli
• Nociceptive neuron


  A sensory neuron that responds to noxious (painful) stimuli
• Nociceptive pain


  Pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors

  
• Nociceptive stimulus


  A stimulus that is damaging or threatens damage to normal tissues
• Nociceptor


  A sensory receptor that responds to stimuli that have the potential to cause tissue damage