Which neurotransmitter is primarily responsible for pain modulation in the dorsal horn of the spinal cord via activation of opioid receptors?

Explanation

## Pain Modulation and Endogenous Opioids **Key Point:** Endorphins (endogenous opioids) are the primary neurotransmitters responsible for descending pain inhibition in the spinal dorsal horn. They bind to μ (mu), δ (delta), and κ (kappa) opioid receptors on nociceptive neurons and interneurons, causing hyperpolarization and reduced neurotransmitter release. ### Mechanism of Action Endorphins are released from: - Periaqueductal gray (PAG) neurons - Rostral ventromedial medulla (RVM) neurons - Local dorsal horn interneurons They act presynaptically to inhibit substance P and glutamate release from primary nociceptive afferents, and postsynaptically to hyperpolarize second-order nociceptive neurons. ### Descending Pain Inhibitory Pathways ```mermaid flowchart TD A[Noxious stimulus]:::outcome --> B[Dorsal horn nociceptors]:::outcome B --> C[Activation of PAG and RVM]:::action C --> D[Endorphin release in dorsal horn]:::action D --> E[Inhibition of pain transmission]:::outcome E --> F[Reduced pain perception]:::outcome ``` **High-Yield:** The descending inhibitory system explains why pain perception is not purely determined by noxious input — emotional state, attention, and expectation modulate pain through endorphin release. **Clinical Pearl:** This is the basis for opioid analgesia and why endogenous opioid antagonists (naloxone) can reverse pain relief.