Which neurotransmitter is released by inhibitory interneurons in the dorsal horn and is responsible for presynaptic inhibition of nociceptive afferents?

Explanation

## Presynaptic Inhibition in the Dorsal Horn **Key Point:** GABA is the primary inhibitory neurotransmitter responsible for presynaptic inhibition of nociceptive afferents (C-fibers and Aδ-fibers) in the dorsal horn of the spinal cord. ### Mechanism of GABAergic Presynaptic Inhibition GABAergic interneurons in laminae I–II (substantia gelatinosa) form axoaxonic synapses on the presynaptic terminals of primary nociceptive afferents. GABA acts on: - **GABA-A receptors** (ionotropic Cl⁻ channels) → membrane hyperpolarization → reduced action potential propagation into the terminal - **GABA-B receptors** (metabotropic, Gi-coupled) → decreased Ca²⁺ influx → reduced vesicular release of substance P and glutamate This is the classical gate-control mechanism at the spinal level, reducing nociceptive signal transmission to second-order neurons. ### Why Not Glycine? Glycine is indeed an important inhibitory neurotransmitter in the spinal cord and brainstem, but it primarily mediates **postsynaptic inhibition** of dorsal horn neurons rather than presynaptic inhibition of primary afferent terminals. GABA (particularly via GABA-B receptors) is the established mediator of **presynaptic inhibition** of nociceptive afferents. | Feature | GABA | Glycine | |---------|------|---------| | **Primary inhibitory role in dorsal horn** | Presynaptic inhibition of afferents | Postsynaptic inhibition of neurons | | **Receptor** | GABA-A (Cl⁻) / GABA-B (Gi) | Glycine receptor (Cl⁻) | | **Nociceptive modulation** | Reduces transmitter release from C/Aδ terminals | Hyperpolarizes postsynaptic projection neurons | | **Antagonist** | Bicuculline (GABA-A), Baclofen agonist (GABA-B) | Strychnine | **High-Yield:** GABA-B receptor agonist **baclofen** is used clinically to reduce spasticity and pain by enhancing presynaptic inhibition of nociceptive afferents — a direct pharmacological correlate of this mechanism. **Clinical Pearl:** Loss of GABAergic inhibition in the dorsal horn contributes to central sensitization and allodynia seen in neuropathic pain states. GABA-A and GABA-B modulators (e.g., benzodiazepines, baclofen, gabapentinoids) are therefore analgesic adjuncts. [cite: Guyton and Hall 14e Ch 48; Kandel Principles of Neural Science 6e Ch 24]