Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry.

THE evaluation of pain in the human fetus and neonate is difficult because pain is generally defined as a subjective phenomenon.1 Early studies of neurologic development concluded that neonatal responses to painful stimuli were decorticate in nature and that perception or localization of pain was not present.2 Furthermore, because neonates may not have memories of painful experiences, they were not thought capable of interpreting pain in a manner similar to that of adults.3 4 5 On a theoretical basis, it was also argued that a high threshold of painful stimuli may be adaptive in protecting infants from pain during birth.6 These traditional . . .

Pain and its effects in the human neonate and fetus

Distribution of substance P-like immunoreactivity in the central nervous system of the rat—I. Cell bodies and nerve terminals

Nervous connections between the trigeminal ganglia and cerebral blood vessels have recently been identified in experimental animals and have been termed the trigeminovascular system. Existence of this system in humans is inferential. Trigeminovascular neurons and their peripheral unmyelinated nerve fibers contain the neurotransmitter peptide substance P. Most newly synthesized substance P is transported from ganglion cell bodies to afferent nerve fibers, where depolarization-induced release of neurotransmitter into the wall of the cerebral blood vessel occurs. Substance P dilates pial arteries, increases vascular permeability, and activates cells that participate in the inflammatory response. The relationship of trigeminovascular fibers to the pathogenesis of vascular head pain sheds light on possible mechanisms of migraine and other central nervous system conditions associated with headache and inflammation.

The neurobiology of vascular head pain.

Immunohistochemical evidence of substance P-like immunoreactivity in some 5-hydroxytryptamine-containing neurons in the rat central nervous system.

THE undecapeptide substance P (SP) may act as a transmitter released from the terminals of primary sensory nerves in the spinal cord1–2. SP has been shown to be highly concentrated in the terminals of small diameter fibres in the substantia gelatinosa of the dorsal horn in mammalian spinal cord, and these terminals disappear after dorsal root section3–6. Sensory nuclei of some of the cranial nerves, such as the spinal trigeminal nucleus, also contain a high density of SP nerve terminals6–7. SP is released by a calcium-dependent mechanism from the isolated rat spinal cord during electrical stimulation of the dorsal roots8. The peptide is also a powerful excitant of neurones in the spinal cord2, and seems to excite selectively those cells in dorsal horn that respond to noxious stimuli9–10. SP may, therefore, represent the excitatory transmitter, or one of the transmitters, released from primary fibres involved in the transmission of pain. We have examined the stimulus-evoked release of SP from rat spinal trigeminal nucleus slices in vitro to explore the factors which may control its release from primary sensory terminals. We report here that opiate analgesics are able to suppress the stimulus-evoked release of SP. These findings may represent a mechanism for the direct spinal analgesic actions of opiates.

T. M. Jessell

Papers

Opiate analgesics inhibit substance P release from rat trigeminal nucleus.

Opiate analgesics inhibit substance P release from rat trigeminal nucleus