Spinal nociception Mechanisms

Spinal nociception Mechanisms

This is part 3 of a lecture on?Spinal Cord Circuits and Pain Gating?that I give at the?University of Zurich.

The first part of the lecture focussed on Nociceptive circuits anatomy. Part 2 is about Spinal Neurotransmission and Neuromodulation.

Here you will learn how spinal neurons regulate pain perception and how small changes in a fine balance between excitation and inhibition can lead to pathological conditions.


Pain normally scales with stimulus intensity. However, many conditions can the curve can lead to this curve shifting, leading to either:

?Allodynia: pain elicited by innocuous stimuli

?Hyperalgesia: increased pain in response to a noxious stimulus

?Spontaneous (ongoing) pain: pain in the absence of stimulus

Allodynia and Hyperalgesia


While many factors can contribute to the development of hypersensitivity, neuropathic pain is often linked to nociceptor (primary sensory neurons) hyperactivity. These neurons often become hyperactive upon nerve damage, which sometimes persists even after healing.

Primary afferent hyperactivity (


Neuronal synapses are subject to long-term plasticity changes caused by hyperactivity, which can increase the efficiency of transmission between nociceptors and spinal cord projection neurons.

Associative synaptic plasticity


A simple experiement demonstrates the importance of intact inhibition in spinal circuits: upon pharmacoloical blockade of inhibition (GABA and Glycine receptors), the amount of excitatory current that reaches projection neurons in the spinal cord is greatly increased, even in response to the stimulation of fiber typically only involved in touch sensation.

Loss of inhibition: proof of principle


It follows that the depletion of inhibitory neurons like glycinergic spinal neurons leads to hypersensivity to normally innocuous stimuli, and even to spontaneous pain-like behavior in mice.

Loss of inhibition (in vivo)


Following the observation that touch can inhibit pain in some instances, a theory was made in 1960 called the "gate control theory" based on existing knowledge of the spinal cord anatomy. This theory has been verified again adn again and refined over time:

Projection neurons (nociceptive) receive input from both nociceptive and non-nociceptive fibers. Non-nociceptive fibers recruit inhibitory interneurons, suppressing projection neurons output.

?→ Low-threshold fiber activation (touch) attenuates pain (touch closes the gate)

→ Loss of spinal inhibition leads to the interpretation of innocuous sensory inputs as noxious (allodynia)

The gate control theory (









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