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.
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