Substance P: Depletion in the dorsal horn of rat spinal cord after section of the peripheral processes of primary sensory neurons

Jessell, Thomas M.; Tsunoo, Akinobu; Kanazawa, Ichiro; Otsuka, Masanori

doi:10.1016/0006-8993(79)90167-7

Cited by 440 publications

(94 citation statements)

References 31 publications

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“…Author manuscript; available in PMC 2016 February 24. 567,1220). This is consistent with the preferential immunohistochemical localization of substance P to capsaicin-sensitive sensory neurons associated with small fibers in the C and Aδ range that carry nociceptive inputs and terminate primarily in the dorsal horn, and its absence in muscle afferents that project monosynaptically to spinal motoneurons (493,812).…”

Section: Functional Role Of Trh In Modulating Motoneuronal Excitabilisupporting

confidence: 79%

Synaptic Control of Motoneuronal Excitability

Rekling

Funk

Bayliss

et al. 2000

Physiological Reviews

537

482

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Movement, the fundamental component of behavior and the principal extrinsic action of the brain, is produced when skeletal muscles contract and relax in response to patterns of action potentials generated by motoneurons. The processes that determine the firing behavior of motoneurons are therefore important in understanding the transformation of neural activity to motor behavior. Here, we review recent studies on the control of motoneuronal excitability, focusing on synaptic and cellular properties. We first present a background description of motoneurons: their development, anatomical organization, and membrane properties, both passive and active. We then describe the general anatomical organization of synaptic input to motoneurons, followed by a description of the major transmitter systems that affect motoneuronal excitability, including ligands, receptor distribution, pre-and postsynaptic actions, signal transduction, and functional role. Glutamate is the main excitatory, and GABA and glycine are the main inhibitory transmitters acting through ionotropic receptors. These amino acids signal the principal motor commands from peripheral, spinal, and supraspinal structures. Amines, such as serotonin and norepinephrine, and neuropeptides, as well as the glutamate and GABA acting at metabotropic receptors, modulate motoneuronal excitability through pre-and postsynaptic actions. Acting principally via second messenger systems, their actions converge on common effectors, e.g., leak K + current, cationic inward current, hyperpolarization-activated inward current, Ca 2+ channels, or presynaptic release processes. Together, these numerous inputs mediate and modify incoming motor commands, ultimately generating the coordinated firing patterns that underlie muscle contractions during motor behavior.

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Section: Functional Role Of Trh In Modulating Motoneuronal Excitabilisupporting

confidence: 79%

Synaptic Control of Motoneuronal Excitability

Rekling

Funk

Bayliss

et al. 2000

Physiological Reviews

537

482

View full text Add to dashboard Cite

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“…In mammals, peripheral nerve section also leads to a marked quantitative decrease of substance P in the dorsal horn (11,16). Data from quantitative immunoelectron microscopy and receptor binding experiments showed that this change resulted from the degeneration of dorsal root afferents (17,18).…”

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confidence: 99%

Substance P immunoreactivity in the lumbar spinal cord of the turtle Trachemys dorbigni following peripheral nerve injury

Partata

Krepsky

Xavier

et al. 2003

Braz J Med Biol Res

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Immunoreactive substance P was investigated in turtle lumbar spinal cord after sciatic nerve transection. In control animals immunoreactive fibers were densest in synaptic field Ia, where the longest axons invaded synaptic field III. Positive neuronal bodies were identified in the lateral column of the dorsal horn and substance P immunoreactive varicosities were observed in the ventral horn, in close relationship with presumed motoneurons. Other varicosities appeared in the lateral and anterior funiculi. After axotomy, substance P immunoreactive fibers were reduced slightly on the side of the lesion, which was located in long fibers that invaded synaptic field III and in the varicosities of the lateral and anterior funiculus. The changes were observed at 7 days after axonal injury and persisted at 15, 30, 60 and 90 days after the lesion. These findings show that turtles should be considered as a model to study the role of substance P in peripheral axonal injury, since the distribution and temporal changes of substance P were similar to those found in mammals. Key wordsPeripheral nerve injury may result in significant changes in neuropeptide production and the development of neuropathic pain behavior (1). In rats, peripheral nerve sectioning leads to a marked quantitative decrease in the nerve of substance P, a peptide of 11 amino acids that is present in small primary afferents and plays an important role in pain sensation (2,3).The chemical structure of substance P is highly conserved in non-mammalian species, and is also found in turtles, animals considered phylogenetically related to the extinct theropsids from which mammals arose (4). Previous studies demonstrated substance P immunoreactivity in the turtle central nervous system (5,6); however, the effects of peripheral axotomy on substance P distribution have not been studied. Therefore, the aim of this study was to determine the effects of sciatic nerve transection on substance P immunoreactive fibers in the lumbar spinal cord of the turtle Trachemys dorbigni.Under ether-induced anesthesia (7), the right sciatic nerve was exposed and transected approximately 5 mm distal to the sciatic notch. In this nerve transection, a 2-mm segment of the nerve was removed to ensure that the transection was complete. Groups of three turtles of both sexes, weighing 300-400 g, were sacrificed 7, 15, 30, 60 and 90 days later. On the final day of the experiment, both operated and control turtles were anesthetized (25 mg/kg Thionembutal, intraperitoneally) and perfused through the heart with cold saline solution followed by 4% paraformaldehyde in 0.1 M sodium phosphate buffer, pH 7.4. The lumbar spinal cord was quickly dissected out, immersed in the same fixative for 2 h and then cryoprotected in 15 and 30% sucrose solutions in phosphate buffer at 4ºC. Coronal serial sections (50 µm) were obtained with a cryostat (Leitz) and collected in cold phosphate-buffered saline (PBS). The sections were then treated with 3% hydrogen peroxide in 10% methanol for 30 min, washed wit...

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“…Substance P and calcitonin gene-related peptide are downregulated whereas vasoactive intestinal peptide and galanin are upregulated (15)(16)(17)(18)(19)(20). We have recently demonstrated that the vasoactive intestinal peptide level is increased in the same sensory neurons that previously produced substance P (21) and that vasoactive intestinal peptide took over the role of tachykinins as excitatory mediators of nociceptive input (22).…”

Section: Introductionmentioning

confidence: 99%

Galanin-mediated control of pain: enhanced role after nerve injury.

Wiesenfeld‐Hallin

Langel

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

181

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The endogenous inhibitory role of the neuropeptide galanin in pain transmission and spinal cord excitability was demonstrated by the use of a high-affinity galanin receptor antagonist, M-35 [galanin-(1-13)-bradykinin-(2-9)-amide]. M-35, which displaced 12'I-labeled galanin from membranes of rat dorsal spinal cord with an IC50 of 0.3 nM, dose-dependently antagonized the effect of intrathecal galanin on the flexor reflex. M-35 potentiated the facilitation of the flexor reflex by conditioning stimulation of cutaneous unmyelinated afferents in rats with intact nerves and the potentiating effect of M-35 on the conditioning-stimulation-induced reflex facilitation of the cutaneous unmyelinated afferents was strongly enhanced after axotomy. These results demonstrate that endogenous galanin plays a tonic inhibitory role in the mediation of spinal cord excitability, and it is particularly noteworthy that this function of galanin is remarkably enhanced after peripheral nerve section.The neuropeptide galanin (1) consists of 29 amino acids, has been shown to occur in a relatively small population of dorsal root ganglion cells and spinal cord interneurons (2-4), and may be involved in sensory modulation. Although some reports indicated that intrathecal (i.t.) galanin has a hyperalgesic effect and i.t. galanin antibody produces analgesia (5), overwhelming evidence suggests that galanin primarily has an inhibitory effect in sensory transmission at the spinal level. Thus, i.t. galanin blocks the facilitatory effect of the flexor reflex produced by the conditioning stimulation (CS) of unmyelinated afferents and by i.t. applied excitatory neuropeptides, such as substance P and calcitonin gene-related peptide (6-8). Galanin also selectively depresses spinal nociceptive reflexes in adult and newborn rats with no or very limited effect on the monosynaptic reflex (6, 9, 10). Galanin (i.t.) has been reported to cause analgesia without motor deficits (11) and iontophresis ofgalanin hyperpolarizes dorsal horn neurons (12). Galanin also inhibits the peripheral consequences of antidromic activation of cutaneous unmyelinated (C) afferents, such as the plasma extravasation, mediated by the release of substance P (13,14).Peripheral axotomy has dramatic effects on peptidergic sensory afferents. Substance P and calcitonin gene-related peptide are downregulated whereas vasoactive intestinal peptide and galanin are upregulated (15)(16)(17)(18)(19)(20). We have recently demonstrated that the vasoactive intestinal peptide level is increased in the same sensory neurons that previously produced substance P (21) and that vasoactive intestinal peptide took over the role of tachykinins as excitatory mediators of nociceptive input (22). We have also shown that the depressive effect of galanin on the flexor reflex is enhanced after nerve section (23) and it antagonized the excitatory effect of vasoactive intestinal peptide, with which it coexists in axotomized sensory neurons (7). Based on these findings, we have hypothesized that one role for upr...

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Substance P: Depletion in the dorsal horn of rat spinal cord after section of the peripheral processes of primary sensory neurons

Cited by 440 publications

References 31 publications

Synaptic Control of Motoneuronal Excitability

Synaptic Control of Motoneuronal Excitability

Substance P immunoreactivity in the lumbar spinal cord of the turtle Trachemys dorbigni following peripheral nerve injury

Galanin-mediated control of pain: enhanced role after nerve injury.

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