Spinal presynaptic inhibition in pain control.

The gate control theory proposed that the nociceptive sensory information transmitted to the brain relies on an interplay between the inputs from nociceptive and non-nociceptive primary afferent fibers. Both inputs are normally under strong inhibitory control in the spinal cord. Under healthy conditions, presynaptic inhibition activated by non-nociceptive fibers modulates the afferent input from nociceptive fibers onto spinal cord neurons, while postsynaptic inhibition controls the excitability of dorsal horn neurons, and silences the non-nociceptive information flow to nociceptive-specific (NS) projection neurons. However, under pathological conditions, this spinal inhibition may be altered and lead to chronic pain. This review summarizes our knowledge of presynaptic inhibition in pain control, with particular focus on how its alteration after nerve or tissue injury contributes to neuropathic or inflammatory pain syndromes, respectively.