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Are glutamate and NMDA involved in increasing or decreasing pain? where there are high levels of...

Are glutamate and NMDA involved in increasing or decreasing pain? where there are high levels of glutamate and when there are increased amount of NMDA receptors then is pain relieved or increased?

also, how is substance P related to pain?

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Answer #1

Pain is mediated in by two type of fibres : C fibres which are slow conducting fibres and A delta fibres which are thinly myelinated . They release glutamate which acts on postsynaptic NMDA receptors leading to their stimulation. This is because glutamate is excitatory neurotransmitter. It sensitizes the nerve to Pain stimuli. So they increase the pain perception.

High level of NMDA activation increase the susceptibility to pain and decrease the sensitiivity of receptors to opiod agonists . Therefore NMDA antagonits also prevent opiod tolerance .

By increased glutamate and nmda receptors , pain is increased

Subtsance P is also released in addition to the glutamate when there occurs cell injury . This induces release of histamine from mast cells and itself acts on NK receptors which reduces the threshold of pain receptors

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