Nociception is the form of somatic sensation that detects potentially tissue-damaging noxious stimuli. Peripheral nociceptors uniquely express transient receptor potentials which are sensitive to potentially-damaging mechanical, chemical, or thermal stimuli. Nociceptors also contain receptors for pain and inflammatory-related mediators or cytokines. Peripheral nociceptors transmit noxious stimuli to the dorsal root ganglia, the dorsal horn, and further to the trigeminal ganglia in the brain. Pain has both a localizing somatic sensory component and an aversive emotional and motivational component. Pain travels through a variety of pathways via first pain on Alpha Delta fibers and second pain on slowly conducting C-fibers.
The dorsal horn of the spinal cord serves as a major integration center for both ascending nociceptive information and descending antinociceptive influences from the brain. Plasticity within the dorsal horn is mediated by NMDA glutamate receptors and key in the initiation of chronic pain by decreasing the excitability threshold in nociceptive pathways. Additionally, damage to neurons in nociceptive pathways leads to neuropathic pain. Three families in northern Pakistan were congenitally unable to perceive pain due to their homozygous loss of function mutation in the SCN9A gene which codes for the voltage-gated sodium channel Na1.7 . This key finding allowed pharmacologists to begin researching if the Na1.7 is a substantial molecular target for analgesic (antipain) medications.
Sensitization, in the clinical sense of the word, is a phenomenon in which nociceptors in an area beyond a tissue injury exhibit decreased thresholds for activation. Sensitization can be initiated by inflammatory prostaglandins or leukotrienes and are therefore the targets of nonsteroidal anti-inflammatory (NSAIDs) which block key enzymes in their synthesis. Additionally, opioid drugs suppress nociceptions by binding to endogenous opioid receptors.