Gate-control theory of pain
Wall and Melzack, 1965
for further review, see Dickenson (2002)
Perception of pain is not simply due to activation of nociceptors, but is the outcome of modulation of both nociceptive and non-nociceptive inputs. According to the gate theory of pain, inhibitory interneurons regulate the transmission of ascending nociceptive information at the level of the second order neuron, allowing modulation of the signal (both increases and decreases in activity are possible). This modulation can explain phantom limb pain, as well as the success of TENS treatment and the actions of opioid analgesics. | ![]() |

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the basic tenet of this theory is that ascending nociceptive signals can be suppressed by the activity of inhibitory interneurons that function as gates to decrease transmission by the second order neurons
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the inhibitory interneurons are thought to be tonically active - therefore, under normal conditions (no external stimuli), neither the C or Aβ fibres are active, the second order neuron is inhibited by the interneuron and no nociceptive signals are sent to the thalamus
- during unmodulated pain, activation of the C fibre causes excitation of the second order neuron as well as inhibition of the inhibitory interneuron, therefore nociceptive information is passed on to the thalamus (i.e., the gate is opened)
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C fibres release the neurotransmitter glutamate (as well as substance P and/or CGRP), which can cause excitation via AMPA receptors or inhibitition via mGLURs - therefore, it is the type of receptor expressed by the postsynaptic cell that determines whether excitation or inhibition occurs
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simultaneous activation of the Aβ fibre reactivates the inhibitory neuron, decreasing the flow of nociceptive signals
and modulation of the pain (i.e., the gate is closed)
- a simple example would be that rubbing your elbow decreases the pain associated with a bumped elbow - rubbing the skin activates large-diameter, myelinated afferents (Aβ) associated with mechanoreceptors, subsequently increasing interneuron activity
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trans-cutaneous electrical nerve stimulation (TENS) is a treatment for pain that also activates this suppression mechanism by delivering a small current to the skin overlying a nerve
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the CNS also has the ability to block pain at the spinal cord level - brainstem neurons that release endorphins are part of an endogenous analgesic system that decrease pain perception due to actions that occur (in part) at the level of the second order neurons
- endogenous opioids (endorphins, enkephalins) act on both the presynaptic (primary afferent) nerve terminal and the postsynaptic cell (2nd order neuron) to decrease nociceptive neurotransmission
- presynaptic actions include a decrease in Ca2+ conductance that results in decreased neurotransmitter release
- postsynaptically, activation of opioid µ receptors causes an increase in K+ conductance (gK+) resulting in an IPSP
- you will hear much more about this system from Dr. Eisenberg!