What are the primary chemical mediators of pain?
At the peripheral pain receptor, mediators of inflamma-tion such as serotonin, histamine, bradykinins, and prosta-glandins decrease nociceptor thresholds, thus sensitizing the receptor to pain. Blocking production of these sub-stances, such as with the use of NSAIDs which decrease prostaglandin production, decreases pain by this peripheral mechanism.
Centrally, substance P, an 11 amino acid peptide, is released in the dorsal horn of the spinal cord, activating the spinothalamic and other ascending pain tracts.
Peripherally, substance-P-releasing axons dilate blood vessels, degranulate mast cells, and stimulate sweat glands, mediating many of the secondary changes associated with pain.
Other physiologic mediators act to inhibit perceived pain stimulation. Endogenous analgesic peptides, such as enkephalins and endorphins, are found throughout the central nervous system and stimulate opioid receptors, inhibiting the release of substance P. These substances are found in the brain, as well as in the descending inhibitory tracks in the dorsal horn of the spinal cord. Neurotransmitters such as serotonin and norepinephrine are also involved in the activation of descending inhibitory tracts.
Amino acids, such as gamma-aminobutyric acid (GABA) and glycine, are known to inhibit synaptic transmission. These neurotransmitters may serve as inhibitory mediators in the substantia gelatinosa.