Spinal Neurotransmission and Neuromodulation

This is part 2 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.

Here you will find an overview of the modes of transmission that allow neuronal communication between neurons within and outside the spinal cord.

In general, a synapse is the physical point of contact that allows transmission of a signal between two neurons.

In the spinal cord and the brain, glutamate is the main excitatory neurotransmitter, the chemical released from pre-synaptic neuron at the synapse that leads to the excitation of the post-synaptic neuron upon binding onto specific receptors.

Neurotransmission can also be inhibitory, meaning the effect of neurotransmitter release from the presynaptic neuron is the suppression of neuronal activity in the porst-synaptic neuron. Inhibitory neurotransmitter in the spinal cord are GABA and Glycine, which again exert their action by binding to specific post-synaptic receptors.

Neurons that release inhibitory neurotransmitters are called inhibitory neurons. While neurons are either excitatory or inhibitory, each neurons's activity is typically shaped excitatory AND inhibitory inputs from thousands of pre-synaptic neurons, and in turn contacts thousands of neurons downstream.

On top of excitatory and inhibitory neurotransmission, neuromodulators are released from the pain into the spinal cord, not necessarily at a synapse, and have various effects on spinal neurons's activity dependending on what receptors they bind to.

Finally, neuropeptides such as endogenous opiods are realeased locally in the spinal cord and from the brainstem.

For exeample, enkephalin, an endogenous opioid (as opposed to exogenous opioids like morphine) is released from specialized spinal neurons and blocks neurotransmission between nociceptive input from the periphery and spinal neurons.

During intense stress, typically life-threatening situations, endogenous opioid are able to block nociception altogether to allow to brain to focus on survival strategies rather than pain.