Nociception

Nociception is the nervous system's process of detecting and transmitting signals about actual or threatened tissue damage, which the brain may or may not experience as pain.

The process begins at nociceptors, free nerve endings in skin, muscle, joints and internal organs that respond to intense heat or cold, mechanical pressure and chemicals released by injured or inflamed tissue. These endings carry receptor proteins such as TRPV1, which senses heat and capsaicin, and TRPA1, which senses irritants. Signals travel along fast myelinated A-delta fibers, producing sharp first pain, and slow unmyelinated C fibers, producing dull aching second pain, to the dorsal horn of the spinal cord and onward to the thalamus and cortex.

Nociception and pain are not the same thing. Signals can be generated without conscious pain, as under anesthesia, and pain can occur without ongoing nociception, as in phantom limb pain. Between the two sit gates that amplify or dampen the message, including descending pathways from the brainstem and local inflammatory changes that lower the threshold of nociceptors, a process called peripheral sensitization. In the laboratory, nociception is measured by reflex withdrawal thresholds in animals and by quantitative sensory testing in people. Cannabinoid receptors and TRP channels are present along the nociceptive pathway, and cannabinoids have been studied for effects on nociception, mostly in preclinical work.