Pain Transduction

Overview of Nociception

• Nociception: The process of detecting and responding to pain.
• Four Phases:
  1. Transduction: Conversion of painful stimuli into electrical signals.
  2. Transmission: Electrical signals travel to the brain via neurons.
  3. Perception: Conscious awareness of pain when it reaches the somatosensory cortex.
  4. Modulation: Central nervous system mechanisms to modify pain signals.

Focus on Transduction

• Nociceptors:
  • Pain receptors capable of generating an action potential.
  • Activated by various stimuli causing the depolarization of the nociceptor.
  • Referred to as polymodal receptors due to multiple stimuli types activating them.

Types of Stimuli

• Mechanical stimuli (e.g., trauma).
• Chemical exposure.
• Tissue ischemia (lack of oxygen).
• Temperature extremes.

Mechanism of Transduction

• Ion Channels:
  • Sodium and calcium channels open, allowing depolarization.
  • Mechanical stress (e.g., puncture) opens mechanically gated ion channels.
  • Heat above 43°C or 109°F opens heat-sensitive ion channels.

Biochemical Mediators

• Damaged cells release substances that depolarize nociceptors:

  • Proteases convert kinins into bradykinin, binding to G-protein-coupled receptors.
  • ATP from damaged cells closes ATP-sensitive potassium channels.
  • Extracellular potassium depolarizes nociceptors.
  • Lactic acid increases hydrogen ions activating acid-sensing ion channels.

• Histamine and Serotonin released during allergic reactions like bee stings activate nociceptors.

• Prostaglandins increase cyclic GMP and sensitize nociceptors by phosphorylating sodium channels.

Additional Chemical Influences

• Calcitonin Gene-Related Peptide (CGRP) and Substance P:

  • Released due to nociceptor activity, amplifying inflammatory response and vasodilation.

• Capsaicin:

  • Activates VR1 receptors, which also respond to heat and acid.
  • Desensitizes pain fibers and prevents substance P release.
  • Utilized in capsaicin creams for pain relief.

Practical Applications

• Development of capsaicin-laced birdseed to deter squirrels.
• Capsaicin creams for treating pain associated with:
  • Shingles
  • Arthritis
  • Mastectomy
  • Trigeminal neuralgia

Conclusion

• Pain transduction leads to the generation of action potentials that travel to the brain, creating a conscious awareness of pain.