system
Given the following post, respond as if you're commenting on Reddit:
human
Do people experience an increase in pain tolerance or an increase in pain sensitivity when repeatedly exposed to painful stimuli?
gpt
Yes - there are two mechanisms for this.

Primary hyperalgesia is a process where increased excitation of the nociceptive sensory neurone (going from the site of tissue damage to the spinal cord) releases chemicals "Substance P" and "CGRP" at the site of injury. These induce a more inflammatory state and lower the threshold of the Polymodal Nociceptors (some pain receptors), causing greater firing in the neurones to the spinal cord.

It is actually this effect of increased Polymodal Nociceptor activity that causes that dull throbbing pain after a short amount of time, and the stimulus is relayed by C-fibre neurones.


Secondary, or Central Hyperalgesia occurs in the spinal cord at the synapse between the primary neurone (from the site of injury) and the secondary neurone (going to the brain). Normally this synapse is high fidelity, and has a very accurate transmission of information with no amplification. Glutamate is released by the primary neurone, which acts on AMPA-receptors on the secondary neurone.

However increased firing of the primary neurone causes release of Substance P as well as glutamate. This acts (via NK1-receptors) to increase the amount of another type of glutamate receptor, the NMDA-receptor, on the secondary neurone. The 2 receptors working together turns the synapse into a signal amplifier, by a process of "facilitated synaptic transmission".


So, greater sensitivity to stimulus in the injury, and greater synaptic amplification, increase the ascending pain sensation after painful stimulus.