Time course of substance P expression in dorsal root ganglia following complete spinal nerve transection

Weissner, Wendy; Winterson, Barbara J.; Stuart-Tilley, Alan K.; Devor, Marshall; Bove, Geoffrey M.

doi:10.1002/cne.20981

Cited by 55 publications

(45 citation statements)

References 90 publications

(98 reference statements)

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“…Initially, an increase is found in the number of both small and large diameter DRG neurons expressing SP (Neumann et al 1996;Weissner et al 2006). However, in the nerve injury models this primary increase later tend to decrease below basal levels for small diameter DRG neurons (Neumann et al 1996;Weissner et al 2006). With time, the decreased spinal levels of SP may be partially recovered (Himes and Tessler 1989).…”

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confidence: 93%

“…These models have shown that the expression levels of the primary afferent neurotransmitters change in response to the painful insult. Initially, an increase is found in the number of both small and large diameter DRG neurons expressing SP (Neumann et al 1996;Weissner et al 2006). However, in the nerve injury models this primary increase later tend to decrease below basal levels for small diameter DRG neurons (Neumann et al 1996;Weissner et al 2006).…”

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confidence: 95%

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Spinal Astrogliosis in Pain Models: Cause and Effects

Hald

2009

Cell Mol Neurobiol

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Pathological pain has been subjected to intense research to shed light on the underlying mechanisms of key symptoms, such as allodynia and hyperalgesia. The main focus has by and large concerned plasticity of spinal cord neurons and the primary afferent nerves relaying peripheral information to the spinal cord. Animal pain models display an increased presence of reactive astrocytes in the spinal cord, but in contrast to neurons, little is known about how they contribute to abnormal pain sensation. However, astrocytes are now beginning to receive greater attention, and as new information is emerging, it appears that astrocytes undertake critical roles in manifesting pathological pain. Through the secretion of diffusible transmitters, such as interleukins, ATP, and NO, astrocytes may augment primary afferent neuronal signaling or sensitize second order neurons in the spinal cord. In addition, astrocytes might lead to altered pain perception by a direct modulation of synaptic transmission between neurons in the nociceptive pathway or through the creation of astrocytic networks capable of transducing signals for extended distances across and along the spinal cord. Future research in astrocyte activation and signaling may therefore reveal novel drug targets for managing pathological pain.

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confidence: 93%

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confidence: 95%

Spinal Astrogliosis in Pain Models: Cause and Effects

Hald

2009

Cell Mol Neurobiol

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“…Here we focused on the neuropeptide, substance P, because it is essential for pain signaling between the dorsal root ganglion (DRG) cells and the spinal cord dorsal horn (McLeod et al 1999;Otsuka and Yanagisawa, 1990;Weissner et al, 2006) and there is limited direct comparison of its relative involvement in mechanical and/or inflammatory insults that produce pain. In peripheral nerve injury, recruitment of macrophages is required for myelin clearance and axonal regeneration Perry et al, 1987) and their secreted inflammatory mediators are highly associated with the pathogenesis of neuropathic pain (Marchand et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Schwann Cell Proliferation and Macrophage Infiltration Are Evident at Day 14 after Painful Cervical Nerve Root Compression in the Rat

Chang

Winkelstein

2011

Journal of Neurotrauma

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Although it is known that different types of nerve root insults can produce radicular pain, it is not known whether the neuronal and Schwann cell pathologies in the nerve root vary between inflammation-induced nerve root injury and traumatic compression. This study examined the extent of Wallerian degeneration and associated cellular repair processes in the nerve root in the context of mechanical hyperalgesia resulting from different modes of painful nerve root injury. The C7 dorsal nerve root underwent a transient 10 gram-force compression (10g), inflammation-induced irritation by chromic gut exposure (Cg), or a combination of those stimuli (10g + Cg). Fourteen days after injury when hyperalgesia remained, immunohistochemical analysis revealed upregulation of substance P, robust macrophage infiltration, myelin degeneration and debris removal, and a significant increase in the number of myelinating Schwann cells (Krox20-positive) in the compressed roots (10g, 10g + Cg). Cg alone also produced hyperalgesia, despite being associated with intact myelin. Unilateral exposure to chromic material induced bilateral increases in macrophages and Krox20-positive Schwann cells in the nerve roots, and substance P expression in the dorsal root ganglion (DRG) neurons. Results suggest that despite similar sensitivity, the extent of infiltrating macrophages and repopulated Schwann cells varies for pain from mechanical and/or chemical nerve root injury. Although these different cellular mechanisms may explain pain, they may also only reflect varying injury etiologies. Disciplines Biomedical Engineering and Bioengineering AbstractAlthough it is known that different types of nerve root insults can produce radicular pain, it is not known whether the neuronal and Schwann cell pathologies in the nerve root vary between inflammation-induced nerve root injury and traumatic compression. This study examined the extent of Wallerian degeneration and associated cellular repair processes in the nerve root in the context of mechanical hyperalgesia resulting from different modes of painful nerve root injury. The C7 dorsal nerve root underwent a transient 10 gram-force compression (10g), inflammation-induced irritation by chromic gut exposure (Cg), or a combination of those stimuli (10g + Cg). Fourteen days after injury when hyperalgesia remained, immunohistochemical analysis revealed upregulation of substance P, robust macrophage infiltration, myelin degeneration and debris removal, and a significant increase in the number of myelinating Schwann cells (Krox20-positive) in the compressed roots (10g, 10g + Cg). Cg alone also produced hyperalgesia, despite being associated with intact myelin. Unilateral exposure to chromic material induced bilateral increases in macrophages and Krox20-positive Schwann cells in the nerve roots, and substance P expression in the dorsal root ganglion (DRG) neurons. Results suggest that despite similar sensitivity, the extent of infiltrating macrophages and repopulated Schwann cells varies for pain from mecha...

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“…However, treating Schwann cell culture alone (b) with DETA-NO caused a significant reduction in PPTA gene expression (***<p=0.0001 compared to vehicle) survival and maintenance of all the subset of DRG neurons, it interacts specifically with nociceptive sensory neurons (see review by Lewin and Mendell 1993), which are trkA, SP, and CGRP positive (Qian et al 1996). Incidentally, absence of NGF from postnatal DRG cultures or axotomy increases nNOS expression in the majority of these nociceptive neurons (Zhang et al 1993;Thippeswamy and Morris 1997a;Renganathan et al 2000;Thippeswamy et al 2001bThippeswamy et al , 2005b in addition to a few large neurons, which may also express SP (Malcangio et al 2000;Weissner et al 2006). Recent evidence suggests that in absence of trkA signaling, NO protects neurons intrinsically by taking over the downstream of NGF-trkA signaling pathway (Culmsee et al 2005;Akassoglou 2005).…”

Section: Discussionmentioning

confidence: 95%

“…Nitric oxide synthase (NOS) catalyze the formation of NO from the substrate L-arginine. In addition to nNOS, galanin and vasoactive intestinal peptide (VIP) are also up-regulated, while substance P (SP) and calcitonin gene-related peptide (CGRP) are downregulated in DRG after axotomy (Doughty et al 1991;Verge et al 1995;Thippeswamy et al 2001aThippeswamy et al , 2007. However, there has been a variation in up-or downregulation of SP after axotomy, which depends on the type/ site and duration of nerve injury and the subpopulation of DRG neurons (Malcangio et al 2000;Siri et al 2001;Wallin and Schott 2002;Weissner et al 2006). SP is known to modulate nociception at the spinal level (Malcangio et al 2000;De Vane 2001), and its expression is mediated by NGF (Wong and Oblinger 1991;Zhang et al 1995;Malcangio et al 2000;Gerard et al 2005).…”

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confidence: 97%

Nitric Oxide-NGF Mediated PPTA/SP, ADNP, and VIP Expression in the Peripheral Nervous System

et al. 2007

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Nerve growth factor (NGF)-deprivation or axotomy of dorsal root ganglion (DRG) neurons causes stress, which they cope by triggering various mechanisms. Among several molecular changes, in the present study, we demonstrate preprotachykinin-A-substance P (PPTA-SP) and activity-dependent neuroprotective protein-vasoactive intestinal peptide (ADNP-VIP) expression pattern using DRG neurons-Schwann cells coculture and axotomy model. In the presence of NGF, DRG cultures showed high levels of PPTA and ADNP mRNA expression, which were significantly suppressed in the absence of NGF and/or nitric oxide synthase (NOS) inhibition by NG-nitro-L-arginine methyl ester (L-NAME), suggesting that both NGF and nitric oxide (NO) can regulate PPTA and ADNP expression. However, treating coculture with NO donor, diethylenetriamine nitric oxide (DETA-NO) did not increase PPTA and ADNP expression in the presence or absence of NGF, although there was a marginal increase in ADNP expression in the absence of NGF. NGF-deprivation increases endogenous NO; thus, DETA-NO had no further effect on PPTA and ADNP expression. Alternatively, NGF produced from NO-stimulated Schwann cells influence gene expression. In addition, interestingly, DETA-NO treatment of Schwann cells alone suppresses both PPTA and ADNP, suggesting differential response of DRG neurons-Schwann cells coculture to DETA-NO. SP and ADNP immunostaining of axotomized DRGs revealed significant reduction in SP and ADNP compared to intact DRG, which was partially recovered in neuronal NOS blocker, 7-nitroindazole (7-NI)-treated DRGs, particularly intense ADNP staining in satellite glia. As ADNP is VIP-responsive gene, we further explored VIP expression in DRGs. Axotomy increased VIP in DRG neurons, but 7-NI treatment caused intense VIP staining in satellite glia. These observations suggest a complex interaction of NO-NGF with PPTA/SP and ADNP-VIP in neuron-glial communication when neurons are stressed.

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Time course of substance P expression in dorsal root ganglia following complete spinal nerve transection

Cited by 55 publications

References 90 publications

Spinal Astrogliosis in Pain Models: Cause and Effects

Spinal Astrogliosis in Pain Models: Cause and Effects

Schwann Cell Proliferation and Macrophage Infiltration Are Evident at Day 14 after Painful Cervical Nerve Root Compression in the Rat

Nitric Oxide-NGF Mediated PPTA/SP, ADNP, and VIP Expression in the Peripheral Nervous System

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