It has been observed that electrical stimulation of small diameter peripheral fibers releases substance P which is present in the synaptic vesicles of these fibers. Substance P has been found in the lamina I and substantia gelatinosa of the spinal cord and is believed to be a neurotransmitter mediating nociception. Iontophoretic application of this substance into the tissues has been shown to excite neurons involved in nociception. Another peptide, somatostatin, also is found in sensory fibers and superficial dorsal horn cells. Peripheral nerve stimulation releases this peptide into the cerebrospinal fluid and it has been suggested that somatostatin may be an inhibitory neurotransmitter in nociception. The role of these peptides in nociception still is an active area of research.
Methionine and leucine enkephalin are pentapeptides which are present in the limbic system, hypothalamus, periaqueductal gray, substantia nigra, locus ceruleus, nucleus tractus solitarius, nucleus ambiguus, nucleus raphae magnus, and lateral reticular nucleus. In the spinal cord, enkephalinergic interneurons have been found in the substantia gelatinosa. Enkephalins are present in the synaptosomal fraction of nervous tissue and are rapidly inactivated. These substances are believed to be neurotransmitters or neuromodulators in the central nervous system (CNS). It has been proposed that in the spinal cord, enkephalins are released from the interneurons in the substantia gelatinosa by the activation of descending periaqueductal-raphae magnus-spinal pathway. Raphae magnus includes serotonin (5-hydroxytryptamine) containing cells. Projections from the raphae magnus to the spinal cord may release serotonin as a neurotransmitter in the spinal cord. The latter may release enkephalins from the spinal interneurons. Binding of enkephalins to the specific opiate receptors on the terminals of the nociceptive afferents results in inhibition of the release of substance P. Substance P is believed to be a neurotransmitter in nociception. Enkephalins, therefore, are believed to be modulators of nociception at the spinal level.
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Division of Neurosurgery
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Saint Barnabas Pain Institute
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