Localization and modulation of calcitonin gene-related peptide-receptor component protein-immunoreactive cells in the rat central and peripheral nervous systems

Ma, Weiya; Chabot, Jean‐Guy; Powell, Kelly J.; Jhamandas, Khem; Dickerson, Ian M.; Quirion, Rémi

doi:10.1016/s0306-4522(03)00159-3

Cited by 113 publications

(89 citation statements)

References 43 publications

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“…RCP enhances signaling at the CGRP receptor (26), and in previous studies, expression of RCP correlated with increased CGRP efficacy during gestation (46). A similar up-regulation of the CGRP receptor system has been proposed in the rat dorsal root ganglia and dorsal horn, where RCP expression was shown to be increased following peripheral inflammation (28,47).…”

Section: Discussionsupporting

confidence: 67%

Intraarticular induction of interleukin‐1β expression in the adult mouse, with resultant temporomandibular joint pathologic changes, dysfunction, and pain

Lai

Shaftel

Miller

et al. 2006

Arthritis & Rheumatism

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Objective. To examine the effects of intraarticular induction of interleukin-1␤ (IL-1␤) expression in adult mice.Methods. We used somatic mosaic analysis in a novel transgenic mouse with an inducible IL-1␤ transcription unit. Transgene activation was induced by Cre recombinase in the temporomandibular joints (TMJs) of adult transgenic mice (conditional knockin model). The effects of intraarticular IL-1␤ induction were subsequently evaluated at the cellular, histopathologic, and behavioral levels. Osteoarthritis (OA) manifests as a slowly progressing debilitating disease that affects one or more joints of the body. Clinical symptoms include pain, dysfunction, and swelling and enlargement of the joints. The primary pathologic features of OA are fibrillation and loss of articular cartilage, accompanied by remodeling of subchondral bone. OA seems to be a node of convergence for a number of potentially independent pathologic processes that, ultimately, can lead to joint dysfunction and pain (1). Although the role of inflammation in OA has been long debated (2), recent evidence now confirms proinflammatory cytokines as mediators in this disease (3). For example, the catabolism of OA cartilage is thought to involve the action of proinflammatory cytokines such as interleukin-1 (IL-1)

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Section: Discussionsupporting

confidence: 67%

Intraarticular induction of interleukin‐1β expression in the adult mouse, with resultant temporomandibular joint pathologic changes, dysfunction, and pain

Lai

Shaftel

Miller

et al. 2006

Arthritis & Rheumatism

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“…Thus, the strain differences in heat responsiveness paralleled those in iCGRP content and chemically induced release. The functional link could be the autoreceptors present on many CGRP-containing DRG neurons and responding to CGRP with calcium influx (10)(11)(12). However, is there a causal relation between CGRP and heat sensitivity?…”

Section: Resultsmentioning

confidence: 99%

“…PKA, via the transcription factor cAMP response element-binding protein, enhances expression of pronociceptive genes including the Calca gene itself (7)(8)(9). Moreover, many CGRP-containing sensory neurons in the rat dorsal root ganglion (DRG) are equipped with autoreceptors and respond to CGRP with calcium influx (10)(11)(12). Both activation of PKA and calcium influx are sufficient to induce sensitization to heat of nociceptive neurons and to enhance their stimulated release of CGRP (13)(14)(15)(16).…”

mentioning

confidence: 99%

Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene

Mogil

Miermeister

Seifert

et al. 2005

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

150

109

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Heat sensitivity shows considerable functional variability in humans and laboratory animals, and is fundamental to inflammatory and possibly neuropathic pain. In the mouse, at least, much of this variability is genetic because inbred strains differ robustly in their behavioral sensitivity to noxious heat. These strain differences are shown here to reflect differential responsiveness of primary afferent thermal nociceptors to heat stimuli. We further present convergent behavioral and electrophysiological evidence that the variable responses to noxious heat are due to strain-dependence of CGRP expression and sensitivity. Strain differences in behavioral response to noxious heat could be abolished by peripheral injection of CGRP, blockade of cutaneous and spinal CGRP receptors, or long-term inactivation of CGRP with a CGRP-binding Spiegelmer. Linkage mapping supports the contention that the genetic variant determining variable heat pain sensitivity across mouse strains affects the expression of the Calca gene that codes for CGRP␣.calcitonin gene-related peptide ͉ genetic ͉ Calca ͉ nociceptors ͉ pain H umans display wide individual variability in sensitivity to pain.Although the relative importance of genes versus experience in human pain perception is unclear, recent studies have shown that mouse strains display large differences in behavioral pain sensitivity that are heritable (1). These same studies revealed genetic correlations between baseline thermal nociception and the hypersensitivity states associated with inflammatory and neuropathic pain (2). Of the strains examined, AKR and C57BL͞6 mice displayed the largest and most consistent differences in several different assays of thermal nociception, with AKR being much less sensitive than C57BL͞6. In contrast, AKR mice exhibit more robust heat hyperalgesia after inflammatory or nerve injury (1). Despite our considerable knowledge of the behavioral ''phenomics'' of baseline heat pain and hyperalgesia, there are almost no published data regarding the underlying cellular or molecular mechanisms. Here we show that the observed strain differences in response to thermal stimulation are caused by corresponding differences in the functioning of primary afferent nociceptors. The differences in nociceptor sensitivity, in turn, are caused by the presence of and sensitivity to the neuropeptide calcitonin gene-related polypeptide (CGRP). Finally, linkage mapping revealed a candidate gene likely responsible for the strain difference: Calca, the gene encoding CGRP␣.CGRP␣ is a secretory neuropeptide released from thin nerve fibers at their peripheral and central terminals, which is thought to contribute importantly to neurogenic inflammation in the skin and to central sensitization in the spinal cord (3-6). CGRP acts through a G s protein-coupled receptor complex to activate cAMPdependent protein kinase (PKA). PKA, via the transcription factor cAMP response element-binding protein, enhances expression of pronociceptive genes including the Calca gene itself (7-9). Moreover, many...

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“…RCP-IR neurons are also present in this area (20). Thus, the various components required to generate functional CGRP1, AM1, and AM2 (1) receptors are expressed in dorsal horn neurons.…”

Section: Discussionmentioning

confidence: 99%

“…We also observed that AM22-52 attenuated capsaicin-induced increase in AM levels in the dorsal horn. AM22-52 may thus act on ''autoreceptors'' to regulate the release of AM from nociceptive afferents, as suggested for CGRP (20). The increase in AM-IR induced by capsaicin may result from a direct effect on the synthesis and release of AM and͞or from an indirect action through the stimulation of the production of other inflammatory mediators, which, in turn, act on their receptors on nociceptors to increase AM synthesis and release.…”

Section: The Pi3k͞akt͞gsk3␤ Signaling Pathway Is Involved In Am-inducedmentioning

confidence: 99%

A role for adrenomedullin as a pain-related peptide in the rat

Chabot

Quirion

2006

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

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Localization and modulation of calcitonin gene-related peptide-receptor component protein-immunoreactive cells in the rat central and peripheral nervous systems

Cited by 113 publications

References 43 publications

Intraarticular induction of interleukin‐1β expression in the adult mouse, with resultant temporomandibular joint pathologic changes, dysfunction, and pain

Intraarticular induction of interleukin‐1β expression in the adult mouse, with resultant temporomandibular joint pathologic changes, dysfunction, and pain

Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene

A role for adrenomedullin as a pain-related peptide in the rat

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