Descending Monoaminergic Analgesic Pathway

Introduction

• Pain perception can sometimes be diminished in extreme situations, such as:
  • Soldiers enduring injuries in battle.
  • Athletes pushing through pain during competition.
• This phenomenon is attributed to the endogenous descending monoaminergic analgesic pathway.

Key Components of the Pathway

• Neurotransmitters involved:
  • Serotonin (5-hydroxytryptamine)
  • Noradrenaline
• Pathway Characteristics:
  • Descending pathway: signals travel from higher brain centers to the spinal cord.
  • Monoaminergic: involves monoamine neurotransmitters.

Pathway Mechanism

1. Higher Centers:
   • Emotions and impulses converge at the periaqueductal gray area (PAG) in the midbrain.
2. Projection Neurons:
   • PAG stimulates projection neurons that descend to spinal cord.
3. Locus Coeruleus (pons):
   • Releases noradrenergic neurotransmitters.
4. Raphe Nucleus:
   • Releases serotonergic neurotransmitters.

Spinal Cord Level Interaction

• Both noradrenaline and serotonin interact with enkephalinergic interneurons, which are inhibitory.
• These interneurons inhibit pain transmission via projection neurons, reducing pain perception.

Sensory Input and Opioids

• Without opioids:
  • Nociceptor sensory neurons activate, releasing glutamate.
  • Glutamate stimulates projection neurons via AMPA and NMDA receptors, causing pain perception.
• With opioids:
  • Stimulation of enkephalinergic interneurons occurs, which release enkephalins.
  • Enkephalins act on opioid receptors, leading to:
    • Reduced sensory input.
    • Hyperpolarization of projection neurons, diminishing depolarization.
  • Overall decrease in pain perception.

Conclusion

• The descending monoaminergic pathway is crucial in modulating pain perception through complex interactions involving higher centers, neurotransmitters, and spinal cord mechanisms.
• Understanding this pathway can help in developing pain management strategies.