Presynaptic inhibition

To test whether somatosensation, specifically pain, was subjected to inhibition, scientists injected a chemical into the spinal cord of a rodent to block the primary inhibitory neurotransmitter's activity (bicuculline, a GABA receptor agonist[4]).

[5] The method by which GABA modulates synaptic transmission from primary afferent fibers to their downstream targets is disputed (see Mechanisms section below).

One study showed that animals without a specific type of GABA receptor on their nociceptors were hypersensitive to pain,[6] thus supporting a function of presynaptic inhibition as an analgesic.

In addition to dampening pain, impaired presynaptic inhibition has been implicated in many neurological disorders, such as spasticity after spinal cord injury,[7] epilepsy, autism, and fragile-X syndrome.

In addition to the presence of GABA receptors along sensory afferent axons, the presynaptic terminal also has a distinct ionic composition that is high in chloride concentration.