The role of calcitonin gene-related peptide (CGRP) in the generation and maintenance of mechanical allodynia and hyperalgesia in rats after intradermal injection of capsaicin

Sun, Rui; Lawand, Nada; Willis, William D.

doi:10.1016/s0304-3959(03)00008-3

Cited by 107 publications

(76 citation statements)

References 39 publications

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“…Repression of CGRP expression may be clinically important given the role of CGRP in inflammatory and neuropathic pain (van Rossum et al, 1997;Ma and Quirion, 2006). For example, CGRP has been reported to play an important role in the initiation and maintenance of capsaicin-induced secondary allodynia and hyperalgesia and, thus, in the development of central sensitization in response to peripheral inflammation (Sun et al, 2003). In addition, results from in vivo studies have demonstrated that CGRP contributes to nociceptive behavior associated with inflammation (Han et al, 2005;Ambalavanar et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract

Abbey

Patil

Vause

et al. 2008

Journal of Ethnopharmacology

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Ethnopharmacological relevance-Cocoa bean preparations were first used by the ancient Maya and Aztec civilizations of South America to treat a variety of medical ailments involving the cardiovascular, gastrointestinal, and nervous systems. Diets rich in foods containing abundant polyphenols, as found in cocoa, underlie the protective effects reported in chronic inflammatory diseases. Release of calcitonin gene-related peptide (CGRP) from trigeminal nerves promotes inflammation in peripheral tissues and nociception.Aim of the study-To determine whether a methanol extract of Theobroma cacao L. (Sterculiaceae) beans enriched for polyphenols could inhibit CGRP expression, both an in vitro and an in vivo approach was taken.Results-Treatment of rat trigeminal ganglia cultures with depolarizing stimuli caused a significant increase in CGRP release that was repressed by pretreatment with Theobroma cacao extract. Pretreatment with Theobroma cacao was also shown to block the KCl-and capsaicin-stimulated increases in intracellular calcium. Next, the effects of Theobroma cacao on CGRP levels were determined using an in vivo model of temporomandibular joint (TMJ) inflammation. Capsaicin injection into the TMJ capsule caused an ipsilateral decrease in CGRP levels. Theobroma cacao extract injected into the TMJ capsule 24 h prior to capsaicin treatment repressed the stimulatory effects of capsaicin.Conclusions-Our results demonstrate that Theobroma cacao extract can repress stimulated CGRP release by a mechanism that likely involves blockage of calcium channel activity. Furthermore, our findings suggest that the beneficial effects of diets rich in cocoa may include suppression of sensory trigeminal nerve activation.

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Section: Discussionmentioning

confidence: 99%

Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract

Abbey

Patil

Vause

et al. 2008

Journal of Ethnopharmacology

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“…Supporting a role for CGRP in this form of trigeminal plasticity is the observation that the CGRP receptor antagonist CGRP reduces mechanical allodynia and hyperalgesia in rat. 105 Finally, CGRP may modulate neuronal function through interaction with glial CGRP receptors. 106 CGRP is thought to be secreted by neurons and then to activate the surrounding glia cells to express molecules such as nitric oxides, which in turn can activate many pronociceptive mediators This modulating effect of CGRP on glial function is not only limited to trigeminal ganglia, but has also been demonstrated in other brain areas, such as the cerebellum [107][108][109][110] and neuromuscular junctions.…”

Section: How Do Cgrp Antagonists Act In Migraine?mentioning

confidence: 99%

CGRP Receptor Antagonism and Migraine

Edvinsson

2010

Neurotherapeutics

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Summary: Calcitonin gene-related peptide (CGRP) is expressed throughout the central and peripheral nervous systems, consistent with control of vasodilatation, nociception, motor function, secretion, and olfaction. ␣CGRP is prominently localized in primary spinal afferent C and A⌬ fibers of sensory ganglia, and ␤CGRP is the main isoform in the enteric nervous system. In the CNS there is a wide distribution of CGRP-containing neurons, with the highest levels occurring in striatum, amygdala, colliculi, and cerebellum. The peripheral projections are involved in neurogenic vasodilatation and inflammation, and central release induces hyperalgesia. CGRP is released from trigeminal nerves in migraine. Trigeminal nerve activation results in antidromic release of CGRP to cause non-endothelium-mediated vasodilatation. At the central synapses in the trigeminal nucleus caudalis, CGRP acts postjunctionally on second-order neurons to transmit pain signals centrally via the brainstem and midbrain to the thalamus and higher cortical pain regions. Recently developed CGRP receptor antagonists are effective at aborting acute migraine attacks. They may act both centrally and peripherally to attenuate signaling within the trigeminovascular pathway.

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“…Noxious mechanical and thermal stimuli evoke the release of CGRP from the superficial dorsal horn (Morton and Hutchison, 1989), and carrageenan inflammation enhances CGRP release (Garry and Hargreaves, 1992). Intrathecal administration of a CGRP-1 receptor antagonist significantly inhibits the development of capsaicin-evoked mechanical allodynia (Sun et al, 2003) Finally αCGRP knockout mice demonstrate a diminished pain behavior in response to capsaicin injection into the hind paw (Salmon et al, 2001). These studies and numerous others demonstrate that CGRP release in the dorsal horn of the spinal cord is a critical component of nociceptive transmission.…”

Section: Hhs Public Accessmentioning

confidence: 99%

Neuropeptide Y inhibits capsaicin-sensitive nociceptors via a Y1-receptor-mediated mechanism

2004

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Neuropeptide Y (NPY) is expressed in certain primary afferent fibers, is up-regulated in response to tissue injury and is capable of inhibiting nociceptive behavior at the spinal level. However, the spinal mechanism(s) for NPY-evoked antinociception is unknown. In this study, we evaluated the hypothesis that agonists at the NPY Y1 receptor subtype (Y1-R) inhibit exocytosis from the capsaicin-sensitive class of nociceptors. Using in vitro superfusion of rat dorsal spinal cord slices, pre-treatment with the Y1-R agonist [Leu 31 Pro 34 ]NPY significantly inhibited capsaicin-evoked release of immunoreactive calcitonin gene-related peptide with an EC 50 value of 10.6 nM. This inhibitory effect was concentration dependent, significantly attenuated by pre-treatment with the Y1 receptor antagonist BIBP3226 and reproduced by synthetic NPY. Examination of adult rat dorsal root ganglia using double immunofluorescent labeling revealed frequent co-localization of Y1 receptor immunoreactivity in vanilloid receptor type 1-immunoreactive neurons, indicating that Y1 agonists may directly modulate the capsaicin-sensitive class of nociceptors. Collectively, these results indicate that NPY is capable of inhibiting capsaicin-sensitive neurons via a Y1 receptor mechanism, suggesting the mechanisms for spinal NPY-induced antinociception is due, at least in part, to inhibition of central terminals of capsaicin-sensitive nociceptors. Keywords superfusion; pain; spinal cord; dorsal root ganglion; exocytosis Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is highly expressed throughout the central and peripheral nervous systems (Balasubramaniam, 1997;Larhammar, 1996;Malstrom, 1997). NPY has been proposed to mediate several physiologic systems including the processing of nociceptive signaling at the level of the spinal cord (Duggan et al., 1991;Mark et al., 1997;Balasubramaniam, 1997;Hokfelt et al., 1998). The NPY Y1 and Y2 receptors are expressed in the dorsal horn of the spinal cord as well as in dorsal root ganglia (DRG) (Kar and Quirion, 1992;Mantyh et al., 1994). The NPY Y1 receptor (Y1-R) is expressed primarily in small-and medium-sized neurons that express calcitonin gene related peptide (CGRP) in the DRG as well as in the dorsal spinal cord in inner lamina II . The NPY Y2 receptor is also expressed in DRG neurons, but primarily in large-* Corresponding author. Tel: +1-210-567-6668; fax: +1-210-567-3389. gibbs@uthscsa.edu (J. Gibbs). The intrathecal administration of NPY or its analogs produces both antinociception and antihyperalgesia (Hua et al., 1991;Taiwo and Taylor, 2002). Recent studies utilizing Y1-R knockout mice or specific NPY receptor antagonists indicate that the intrathecal effects of NPY are due primarily to activation of the Y1-R (Naveilhan et al., 2001;Taiwo and Taylor, 2002). However, the target neuronal populations mediating this effect have yet to be determined. HHS Public AccessNumerous studies have demonstrated that CGRP is involved in spinal nociception (see Vasko, 1995; van Rossum et al., 19...

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The role of calcitonin gene-related peptide (CGRP) in the generation and maintenance of mechanical allodynia and hyperalgesia in rats after intradermal injection of capsaicin

Cited by 107 publications

References 39 publications

Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract

Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract

CGRP Receptor Antagonism and Migraine

Neuropeptide Y inhibits capsaicin-sensitive nociceptors via a Y1-receptor-mediated mechanism

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