Calcitonin gene-related peptide promotes mechanical nociception by potentiating release of substance P from the spinal dorsal horn in rats

Oku, Ryoya; Satoh, Masamichi; Fujii, Nobutaka; Otaka, Akira; Yajima, Haruaki; Takagi, Hiroshi

doi:10.1016/0006-8993(87)90074-6

Cited by 341 publications

(138 citation statements)

References 21 publications

Supporting

Mentioning

132

Contrasting

Unclassified

Order By: Relevance

“…CGRP has been reported to increase the release of neurotransmitters from primary afferent fibers, and to regulate the expression of post-synaptic receptors, including the substance P receptor in spinal neurons (Oku et al, 1987;Seybold, 2009;Seybold et al, 2003). Hence, structural alterations in the wiring of the spinal nociceptive network, particularly in relation to CGRP-expressing fibers, may have a strong impact on the processing of noxious and innocuous information.…”

Section: Spinal Gap-43 Expression and Nerve Injurymentioning

confidence: 99%

Neuropathy-Induced Spinal GAP-43 Expression Is Not a Main Player in the Onset of Mechanical Pain Hypersensitivity

Jaken

Gorp

Joosten

et al. 2011

Journal of Neurotrauma

View full text Add to dashboard Cite

Structural plasticity within the spinal nociceptive network may be fundamental to the chronic nature of neuropathic pain. In the present study, the spatiotemporal expression of growth-associated protein-43 (GAP-43), a protein which has been traditionally implicated in nerve fiber growth and sprouting, was investigated in relation to mechanical pain hypersensitivity. An L5 spinal nerve transection model was validated by the presence of mechanical pain hypersensitivity and an increase in the early neuronal activation marker cFos within the superficial spinal dorsal horn upon innocuous hindpaw stimulation. Spinal GAP-43 was found to be upregulated in the superficial L5 dorsal horn from 5 up to 10 days after injury. GAP-43 was co-localized with calcitoningene related peptide (CGRP), but not vesicular glutamate transporter-1 (VGLUT-1), IB4, or protein kinase-c (PKC-c), suggesting the regulation of GAP-43 in peptidergic nociceptive afferents. These GAP-43/CGRP fibers may be indicative of sprouting peptidergic fibers. Fiber sprouting largely depends on growth factors, which are typically associated with neuro-inflammatory processes. The putative role of neuropathy-induced GAP-43 expression in the development of mechanical pain hypersensitivity was investigated using the immune modulator propentofylline. Propentofylline treatment strongly attenuated the development of mechanical pain hypersensitivity and glial responses to nerve injury as measured by microglial and astroglial markers, but did not affect neuropathy-induced levels of spinal GAP-43 or GAP-43 regulation in CGRP fibers. We conclude that nerve injury induces structural plasticity in fibers expressing CGRP, which is regarded as a main player in central sensitization. Our data do not, however, support a major role of these structural changes in the onset of mechanical pain hypersensitivity.

show abstract

Section: Spinal Gap-43 Expression and Nerve Injurymentioning

confidence: 99%

Neuropathy-Induced Spinal GAP-43 Expression Is Not a Main Player in the Onset of Mechanical Pain Hypersensitivity

Jaken

Gorp

Joosten

et al. 2011

Journal of Neurotrauma

View full text Add to dashboard Cite

show abstract

“…In this study, we employed morphological and immunohistochemical methods to examine the changes of dorsal root ganglion neurons using the same nerve root compression model as in Part 1. In this immunohistochemical study, we investigated SP [32] and CGRP [38,44], which is thought to play a role in pain sensation, and SOM [33], which is believed to be involved in temperature sensation.…”

Section: Introductionmentioning

confidence: 99%

Pathology of lumbar nerve root compression Part 2: Morphological and immunohistochemical changes of dorsal root ganglion

Kobayashi¹,

Yoshizawa²,

Yamada³

2004

Journal Orthopaedic Research

View full text Add to dashboard Cite

Study design: This study is to investigate the changes of dorsal root ganglion (DRG) induced by mechanical compression usingObjectives: The effect of axonal flow disturbance induced by nerve root compression was determined in DRG. Summury of'hackground data: The dorsal root ganglion should not be overlooked when considering the mechanism of low back pain and sciatica, so it is important to understand the morphologic and functional changes that occur in primary sensory neurons of the dorsal root ganglion as a result of nerve root compression. However, few studies have looked at changes of neurons within the dorsal root ganglion caused by disturbance of axonal flow and the axon reaction as a result of mechanical compression of the dorsal root through which the central branches of the primary sensory nerves pass.h4ethod.s: In mongrel dogs, the seventh lumbar nerve root was compressed for 24 h, one week, or three weeks using a clip with a pressure of 7.5 gf. Morphologic changes of the primary sensory neurons in the dorsal root ganglion secondary to the axon reaction were examined by light and electron microscopy. Changes of immunostaining for substance P (SP), calcitonin gene-related peptide (CGRP), and somatostatin (SOM) in the primary sensory neurons affected by central chromatolysis after nerve root compression were also examined.Results: Light microscopy showed central chromatolysis of neurons in the dorsal root ganglion from one week after the start of compression. Electron microscopy of the affected neurons revealed movement of the nucleus to the cell periphery and the loss of rough endo-plasmic reticulum and mitochondria from the central region. Immunohistochemical studies showed a marked decrease of SP, CGRP, and SOM staining in small ganglion cells with central chromatolysis when compared with cells from control ganglia.Conclusion: It is important to be aware that in patients with nerve root compression due to lumbar disc herniation or lumbar canal stenosis, dysfunction is not confined to degeneration at the site of compression, but also extends to the primary sensory neurons within the dorsal root ganglion as a result of the axon reaction. Patients with sensory disturbance should therefore be fully informed of the fact that these symptoms will not resolve immediately after surgery.

show abstract

“…It potentiates the release of substance P from primary afferent terminals and promotes nociceptive information transmission induced by noxious stimuli [49]. CGRP is also implicated in modulating synaptic transmission of glutamate and acetylcholine [50][51][52].…”

Section: Functionmentioning

confidence: 99%

Targeting CGRP: A New Era for Migraine Treatment

Goldberg

Silberstein

2015

CNS Drugs

View full text Add to dashboard Cite

Migraine is a highly prevalent headache disease that typically affects patients during their most productive years. Despite significant progress in understanding the underlying pathophysiology of this disorder, its treatment so far continues to depend on drugs that, in their majority, were not specifically designed for this purpose. The neuropeptide calcitonin gene-related peptide (CGRP) has been indicated as playing a critical role in the central and peripheral pathways leading to a migraine attack. It is not surprising that drugs designed to specifically block its action are gaining remarkable attention from researchers in the field with, at least so far, a safe risk profile. In this article, we highlight the evolution from older traditional treatments to the innovative CGRP target drugs that are revolutionizing the way to approach this debilitating neurological disease. We provide a brief introduction on pathophysiology of migraine and details on the characteristic, function, and localization of CGRP to then focus on CGRP receptor antagonists (CGRP-RAs) and CGRP monoclonal antibodies (CGRP mAbs). Key PointsThe neuropeptide calcitonin gene-related peptide (CGRP) has been indicated as playing a critical role in the central and peripheral pathways leading to a migraine attack.Targeting CGRP as a specific therapeutic tool for migraine may offer similar or even better efficacy than currently available treatments without the vasoconstrictive risk factors.Further studies are necessary to determine the exact role of CGRP receptor antagonists and CGRP monoclonal antibodies in migraine with aura, allodynia, and photophobia.

show abstract

Calcitonin gene-related peptide promotes mechanical nociception by potentiating release of substance P from the spinal dorsal horn in rats

Cited by 341 publications

References 21 publications

Neuropathy-Induced Spinal GAP-43 Expression Is Not a Main Player in the Onset of Mechanical Pain Hypersensitivity

Neuropathy-Induced Spinal GAP-43 Expression Is Not a Main Player in the Onset of Mechanical Pain Hypersensitivity

Pathology of lumbar nerve root compression Part 2: Morphological and immunohistochemical changes of dorsal root ganglion

Targeting CGRP: A New Era for Migraine Treatment

Contact Info

Product

Resources

About