Abstract
Calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) belongs to the calcitonin gene-related peptide (CGRP) family, with a wide range of distribution and biological functions. CGRP is a well known pain transmitter and modulator highly expressed in primary sensory neurons. In this book chapter, we summarize current data on the role of CGRP in nociception and various types of pain conditions. We also discuss the effectiveness of peptide and non-peptide CGRP antagonists in treating these pathological pain states. Unlike CGRP, the role of AM in nociception and pathological pain conditions remains mostly unknown. However, recent anatomical and pharmacological findings suggest its role in nociception and some pain conditions. Future studies are proposed to uncover the mechanisms underlying the contribution of CGRP and AM in nociception and pathological pain conditions. Developing more selective small molecule antagonists of CGRP and AM receptors should thus be considered as promising therapeutic avenue to effectively treat various pain conditions.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- AM:
-
adrenomedullin
- AMPA:
-
alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate
- CB1:
-
cannabinoid 1
- CFA:
-
complete Freund’s adjuvant
- CGRP:
-
calcitonin gene-related peptide
- CLR:
-
calcitonin-like receptor
- CREB:
-
cAMP response element binding protein
- DRG:
-
dorsal root ganglion
- GDNF:
-
glia-derived neurotrophic factor
- GSK3ß:
-
glycogen synthase kinase 3ß
- IB4:
-
isolectin 4
- IL-6:
-
interleukin-6
- IL-1β:
-
interleukin-1β
- LPS:
-
lipopolysccharide
- MAPK:
-
mitogen-activated protein kinase
- NGF:
-
nerve growth factor
- NMDA:
-
N-methyl-D-aspartate
- NO:
-
nitric oxide
- PGE2:
-
prostaglandin E2
- PI3K:
-
phosphatidylinositol 3-kinase
- PKA:
-
protein kinase A
- PKC:
-
protein kinase C
- RAMPs:
-
receptor activity modifying proteins
- RCP:
-
receptor component protein
- SP:
-
substance P
- TRPV1:
-
transient receptor potential vanilloid receptor 1
References
Ai X, Cappuzzello J, Hall AK (1999) Activin and bone morphogenetic proteins induce calcitonin gene-related peptide in embryonic sensory neurons in vitro. Mol Cell Neurosci 14:506–518
Amara SG, Jonas V, Rosenfeld MG et al (1982) Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature 298:240–244
Amara SG, Arriza JL, Leff SE et al (1985) Expression in brain of a messenger RNA encoding a novel neuropeptide homologous to calcitonin gene-related peptide. Science 229:1094–1097
Ambalavanar R, Dessem D, Moutanni A et al (2006a) Muscle inflammation induces a rapid increase in calcitonin gene-related peptide (CGRP) mRNA that temporally relates to CGRP immunoreactivity and nociceptive behavior. Neuroscience 143:875–884
Ambalavanar R, Moritani M, Moutanni A et al (2006b) Deep tissue inflammation upregulates neuropeptides and evokes nociceptive behaviors which are modulated by a neuropeptide antagonist. Pain 120:53–68
Belanger S, Ma W, Chabot J-G, Quirion R (2002) Expression of calcitonin gene-related peptide, substance P and protein kinase C in cultured dorsal root ganglion neurons following chronic exposure to mu, delta and kappa opiates. Neuroscience 115:441–453
Bellamy J, Bowen EJ, Russo AF et al (2006) Nitric oxide regulation of calcitonin gene-related peptide gene expression in rat trigeminal ganglia neurons. Eur J Neurosci 23:2057–2066
Bennett AD, Chastain KM, Hulsebosch CE (2000) Alleviation of mechanical and thermal allodynia by CGRP(8-37) in a rodent model of chronic central pain. Pain 86:163–175
Brain SD, Grant AD (2004) Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev 84:903–934
Bucelli RC, Gonsiorek EA, Kim WY et al (2008) Statins decrease expression of the proinflammatory neuropeptides calcitonin gene-related peptide and substance P in sensory neurons. J Pharmacol Exp Ther 324:1172–1180
Carlton SM, Mcneill DL, Chung K et al (1987) A light and electron microscopic level analysis of calcitonin gene-related peptide (CGRP) in the spinal cord of the primate: an immunohistochemical study. Neurosci Lett 82:145–150
Caterina MJ, Schumacher MA, Tominaga M et al (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824
Caterina MJ, Leffler A, Malmberg AB et al (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306–313
Chabot J-G, Ma W, Trang T et al (2005) Alteration of calcitonin gene-related peptide receptor modifying protein in the dorsal horn of morphine-tolerant rats. Soc Neurosci Abstr 920:6
Chung K, Lee WT, Carlton SM (1988) The effects of dorsal rhizotomy and spinal cord isolation on calcitonin gene-related peptide labeled terminals in the rat lumbar dorsal horn. Neurosci Lett 90:27–32
Cottrell GS, Roosterman D, Marvizon JC et al (2005) Localization of calcitonin receptor-like receptor and receptor activity modifying protein 1 in enteric neurons, dorsal root ganglia, and the spinal cord of the rat. J Comp Neurol 490:239–255
Cridland RA, Henry JL (1988) Effects of intrathecal administration of neuropeptides on a spinal nociceptive reflex in the rat: VIP, galanin, CGRP, TRH, somatostatin and angiotensin II. Neuropeptides 11:23–32
Cruise BA, Xu P, Hall AK (2004) Wounds increase activin in skin and a vasoactive neuropeptide in sensory ganglia. Dev Biol 271:1–10
Doods H, Hallermayer G, Wu D et al (2000) Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist. Br J Pharmacol 129:420–423
Doods H, Arndt K, Rudolf K et al (2007) CGRP antagonists: unravelling the role of CGRP in migraine. Trends Pharmacol Sci 28:580–587
Ebersberger A, Charbel IP, Vanegas H et al (2000) Differential effects of calcitonin gene-related peptide and calcitonin gene-related peptide 8–37 upon responses to N-methyl-D-aspartate or (R, S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate in spinal nociceptive neurons with knee joint input in the rat. Neuroscience 99:171–178
Edvinsson L (2007) Novel migraine therapy with calcitonin gene-regulated peptide receptor antagonists. Expert Opin Ther Targets 11:1179–1188
Edvinsson L, Ekman R, Jansen I et al (1987) Calcitonin gene-related peptide and cerebral blood vessels: distribution and vasomotor effects. J. Cereb Blood Flow Metab 7:720–728
Edvinsson L, Nilsson E, Jansen-Olesen I (2007) Inhibitory effect of BIBN4096BS, CGRP(8-37), a CGRP antibody and an RNA-Spiegelmer on CGRP induced vasodilatation in the perfused and non-perfused rat middle cerebral artery. Br J Pharmacol 150:633–640
Flores CM, Leong AS, Dussor GO et al (2001) Capsaicin-evoked CGRP release from rat buccal mucosa: development of a model system for studying trigeminal mechanisms of neurogenic inflammation. Eur J Neurosci 14:1113–1120
Gallai V, Sarchielli P, Floridi A et al (1995) Vasoactive peptide levels in the plasma of young migraine patients with and without aura assessed both interictally and ictally. Cephalalgia 15:384–390
Gibson SJ, Polak JM, Bloom SR et al (1984) Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and of eight other species. J Neurosci 4:3101–3111
Goadsby PJ, Edvinsson L (1993) The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 33:48–56
Goadsby PJ, Edvinsson L (1994) Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies. Brain 117:427–434
Goadsby PJ, Edvinsson L, Ekman R (1988) Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol 23:193–196
Hanesch U, Schaible HG (1995) Effects of ankle joint inflammation on the proportion of calcitonin gene-related peptide (CGRP)-immunopositive perikarya in dorsal root ganglia. Prog Brain Res 104:339–347
Hobara N, Nakamura A, Ohtsuka A et al (2004) Distribution of adrenomedullin-containing perivascular nerves in the rat mesenteric artery. Peptides 25:589–599
Hokfelt T, Arvidsson U, Ceccatelli S et al (1992) Calcitonin gene-related peptide in the brain, spinal cord, and some peripheral systems. Ann N Y Acad Sci 657:119–134
Hokfelt T, Zhang X, Verge V et al (1993) Coexistence and interaction of neuropeptides with substance-P in primary sensory neurons, with special reference to galanin. Regul Pept 46:76–80
Hong Y, Ma W, Fournier A et al (2007) The role of adrenomedullin in the spinal cord and dorsal root ganglion in inflammatory pain. Soc Neurosci Abstr 184:19
Hong Y, Chen P, Ma W et al. (2008) The involvement of adrenomedullin in the development of morphine tolerance. Soc Neurosci Abstr 270.11
Jacques D, Dumont Y, van Rossum D et al (2000) Calcitonin gene-related peptide (CGRP), amylin and adrenomedullin: anatomical localization and biological functions in the mammalian and human brains. In: Quirion R, Bjorklund A, Hokfelt T (eds) Peptide receptors, Part I, vol 16. Elsevier Science, Amsterdam, pp 301–374
Jang JH, Nam TS, Paik KS et al (2004) Involvement of peripherally released substance P and calcitonin gene-related peptide in mediating mechanical hyperalgesia in a traumatic neuropathy model of the rat. Neurosci Lett 360:129–132
Jhamandas K, Ma W, Trang T et al (2005) Alteration of the pathways of PI3 kinases and MAP kinases in the dorsal horn of morphine-tolerant and dependent rats. Soc Neurosci Abstr 291:6
Kangrga I, Randic M (1990) Tachykinins and calcitonin gene-related peptide enhance release of endogenous glutamate and aspartate from the rat spinal dorsal horn slice. J Neurosci 10:2026–2038
Kitamura K, Kangawa K, Kawamoto M et al (1993) Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun 192:553–560
Kuraishi Y, Nanayama T, Ohno H et al (1988) Antinociception induced in rats by intrathecal administration of antiserum against calcitonin gene-related peptide. Neurosci Lett 92:325–329
Kuwasako K, Cao YN, Nagoshi Y et al (2004) Adrenomedullin receptors: pharmacological features and possible pathophysiological roles. Peptides 25:2003–2012
Lassen LH, Haderslev PA, Jacobsen VB et al (2002) CGRP may play a causative role in migraine. Cephalalgia 22:54–61
Le Greves P, Nyberg F, Terenius L et al (1985) Calcitonin gene-related peptide is a potent inhibitor of substance P degradation. Eur J Pharmacol 115:309–311
Lee SE, Kim JH (2007) Involvement of substance P and calcitonin gene-related peptide in development and maintenance of neuropathic pain from spinal nerve injury model of rat. Neurosci Res 58:245–249
Liang DY, Shi X, Li X et al (2007) The beta2 adrenergic receptor regulates morphine tolerance and physical dependence. Behav Brain Res 181:118–126
Limmroth V, Katsarava Z, Liedert B et al (2001) An in vivo rat model to study calcitonin gene related peptide release following activation of the trigeminal vascular system. Pain 92:101–106
Lindsay RM, Harmar AJ (1989) Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature 337:362–334
Link AS, Kuris A, Edvinsson L (2008) Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system. J Headache Pain 9:5–12
Luebke AE, Dahl GP, Roos BA et al (1996) Identification of a protein that confers calcitonin gene-related peptide responsiveness to oocytes by using a cystic fibrosis transmembrane conductance regulator assay. Proc Natl Acad Sci U S A 93:3455–3460
Ma W, Bisby MA (1998) Increase of calcitonin gene-related peptide immunoreactivity in the axonal fibers of the gracile nuclei of adult and aged rats after complete and partial sciatic nerve injuries. Exp Neurol 152:137–149
Ma W, Quirion R (2006a) Increased calcitonin gene-related peptide in neuroma and invading macrophages is involved in the up-regulation of interleukin-6 and nerve injury associated thermal hyperalgesia in a rat model of mononeuropathy. J Neurochem 98:180–192
Ma W and Quirion R (2006) Lipopolysaccharide induces calcitonin gene-related peptide in Raw 264.7 macrophage cell line and murine peritoneal macrophages. Soc Neurosci Abstr 444:5
Ma W, Ramer MS, Bisby MA (1999) Increased calcitonin gene related peptide immunoreactivity in gracile nucleus after partial sciatic nerve injury: age-dependent and originating from spared sensory neurons. Exp Neurol 159:459–473
Ma W, Zheng W, Kar S et al (2000) Morphine treatment induced calcitonin gene-related peptide and substance P increases in cultured dorsal root ganglion neurons. Neuroscience 99:529–539
Ma W, Zheng WH, Powell K et al (2001) Chronic morphine exposure increases the phosphorylation of MAP kinases and the transcription factor CREB in dorsal root ganglion neurons: an in vitro and in vivo study. Eur J Neurosci 14:1091–1104
Ma W, Chabot JG, Powell KJ et al (2003) Localization and modulation of calcitonin gene-related peptide-receptor component protein-immunoreactive cells in the rat central and peripheral nervous systems. Neuroscience 120:677–694
Ma W, Chabot JG, Quirion R (2006) A role for adrenomedullin as a pain-related peptide in the rat. Proc Natl Acad Sci U S A 103:16027–16032
Ma W, Dumont Y, Quirion R (2009) Lipopolysaccharide induces calcitonin gene-related peptide in the Raw 264.7 macrophage cell line. Submitted
Ma W, Inoue W, Luheshi G et al. (2008) Stimulating the synthesis of pain-related peptide substance P and calcitonin gene-related peptide in nociceptors is a novel mechanism underlying the role of prostaglandin E2 in nociception. Abstr Can Assoc Neurosci. 172.8
Mao J, Coghill RC, Kellstein DE et al (1992) Calcitonin gene-related peptide enhances substance P-induced behaviors via metabolic inhibition: in vivo evidence for a new mechanism of neuromodulation. Brain Res 574:157–163
Marvizon JC, Perez OA, Song B et al (2007) Calcitonin receptor-like receptor and receptor activity modifying protein 1 in the rat dorsal horn: localization in glutamatergic presynaptic terminals containing opioids and adrenergic alpha2C receptors. Neuroscience 148:250–265
McLatchie LM, Fraser NJ, Main MJ et al (1998) RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393:333–339
Mcneill DL, Chung K, Carlton SM et al (1988) Calcitonin gene-related peptide immunostained axons provide evidence for fine primary afferent fibers in the dorsal and dorsolateral funiculi of the rat spinal cord. J Comp Neurol 272:303–308
Menard DP, Vanrossum D, Kar S et al (1996) A calcitonin gene-related peptide receptor antagonist prevents the development of tolerance to spinal morphine analgesia. J Neurosci 16:2342–2351
Merighi A, Polak JM, Gibson SJ et al (1988) Ultrastructural studies on calcitonin gene-related peptide-, tachykinins- and somatostatin-immunoreactive neurones in rat dorsal root ganglion: evidence for the colocalization of different pepitdes in single secretory granules. Cell Tissue Res 254:101–109
Miki K, Fukuoka T, Tokunaga A et al (1997) Calcitonin gene-related peptide increase in the rat spinal dorsal horn and dorsal column nucleus following peirpheral nerve injury: up-regulation in a subpopulation of primary afferent sensory neurons. Neuroscience 82:1243–1252
Mogil JS, Miermeister F, Seifert F et al (2005) Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene. Proc Natl Acad Sci U S A 102:12938–12943
Nahin RL, Byers MR (1994) Adjuvant-induced inflammation of rat paw is associated with altered calcitonin gene-related peptide immunoreactivity within cell bodies and peripheral endings of primary afferent neurons. J Comp Neurol 349:475–485
Natura G, von Banchet GS, Schaible HG (2005) Calcitonin gene-related peptide enhances TTX-resistant sodium currents in cultured dorsal root ganglion neurons from adult rats. Pain 116:194–204
Oku R, Satoh M, Fujii N et al (1987) Calcitonin gene-related peptide promotes mechanical nociception by potentiating release of substance P from the spinal dorsal horn in rats. Brain Res 403:350–354
Ossipov MH, Zhang ET, Carvajal C et al (2002) Selective mediation of nerve injury-induced tactile hypersensitivity by neuropeptide Y. J Neurosci 22:9858–9867
Pedersen-Bjergaard U, Nielsen LB, Jensen K et al (1991) Calcitonin gene-related peptide, neurokinin A and substance P: effects on nociception and neurogenic inflammation in human skin and temporal muscle. Peptides 12:333–337
Powell KJ, Ma W, Sutak M et al. (2000) Blockade and reversal of spinal morphine tolerance by peptide and non- peptide calcitonin gene-related peptide receptor antagonists. Br J Pharmacol 131:875–884
Poyner DR, Sexton PM, Marshall I et al (2002) International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev 54:233–246
Rosenfeld MG, Mermod JJ, Amara SG et al (1983) Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature 304:129–135
Salvatore CA, Hershey JC, Corcoran HA et al (2008) Pharmacological characterization of MK-0974 [N-[(3R, 6S)-6-(2, 3-difluorophenyl)-2-oxo-1-(2, 2, 2-trifluoroethyl)azepan-3- yl]-4-(2-oxo-2, 3-dihydro-1H-imidazo[4, 5-b]pyridin-1-yl)piperidine-1-carbox amide], a potent and orally active calcitonin gene-related peptide receptor antagonist for the treatment of migraine. J Pharmacol Exp Ther 324:416–421
Schorscher-Petcu A, Mogil JS, Quirion R (2007) Pharmacological effects of supraspinal CGRP in pain- and mood-related behaviors in mice. Soc Neurosci Abstr 502:4
Seybold VS, Galeazza MT, Garry MG et al (1995) Plasticity of calcitonin gene related peptide neurotransmission in the spinal cord during peripheral inflammation. Can J Physiol Pharmacol 73:1007–1014
Sivilia S, Paradisi M, D’Intino G et al (2008) Skin homeostasis during inflammation: a role for nerve growth factor. Histol Histopathol 23:1–10
Snider WD, McMahon SB (1998) Tackling pain at the source: new ideas about nociceptors. Neuron 20:629–632
Staton PC, Wilson AW, Bountra C et al (2007) Changes in dorsal root ganglion CGRP expression in a chronic inflammatory model of the rat knee joint: differential modulation by rofecoxib and paracetamol. Eur J Pain 11:283–289
Steenbergh PH, Hoppener JW, Zandberg J et al (1985) A second human calcitonin/CGRP gene. FEBS Lett 183:403–407
Stepien A, Jagustyn P, Trafny EA et al (2003) Suppressing effect of the serotonin 5HT1B/D receptor agonist rizatriptan on calcitonin gene-related peptide (CGRP) concentration in migraine attacks. Neurol Neurochir Pol 37:1013–1023
Sugimoto T, Fujiyoshi Y, Xiao C et al (1997) Central projection of calcitonin gene-related peptide (CGRP)- and substance P (SP)-immunoreactive trigeminal primary neurons in the rat. J Comp Neurol 378:425–442
Sun H, Ren K, Zhong CM et al (2001) Nerve injury-induced tactile allodynia is mediated via ascending spinal dorsal column projections. Pain 90:105–111
Sun RQ, Lawand NB, Willis WD (2003) 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. Pain 104:201–208
Sun RQ, Lawand NB, Lin Q et al (2004a) Role of calcitonin gene-related peptide in the sensitization of dorsal horn neurons to mechanical stimulation after intradermal injection of capsaicin. J. Neurophysiol 92:320–326
Sun RQ, Tu YJ, Lawand NB et al (2004b) Calcitonin gene-related peptide receptor activation produces PKA- and PKC-dependent mechanical hyperalgesia and central sensitization. J Neurophysiol 92:2859–2866
Takhshid MA, Owji AA, Vasei M et al (2004) Expression of spinal cord Fos protein in response to intrathecal adrenomedullin and CGRP in conscious rats. Brain Res 1020:30–36
Takhshid MA, Poyner DR, Chabot JG et al (2006) Characterization and effects on cAMP accumulation of adrenomedullin and calcitonin gene-related peptide (CGRP) receptors in dissociated rat spinal cord cell culture. Br J Pharmacol 148:459–468
Tiong GK, Pierce TL, Olley JE (1992) Sub-chronic exposure to opiates in the rat: effects on brain levels of substance P and calcitonin gene-related peptide during dependence and withdrawal. J Neurosci Res 32:569–575
Trang T, Sutak M, Quirion R et al (2002) The role of spinal neuropeptides and prostaglandins in opioid physical dependence. Br J Pharmacol 136:37–48
Trang T, Ma W, Chabot JG et al (2006) Spinal modulation of calcitonin gene-related peptide by endocannabinoids in the development of opioid physical dependence. Pain 126:256–271
Traub RJ, Solodkin A, Ruda MA (1989) Calcitonin gene-related peptide immunoreactivity in the cat lumbosacreal spinal cord and the effects of multiple dorsal rhizotomies. J Comp Neurol 287:225–237
Troconiz IF, Wolters JM, Tillmann C et al (2006) Modelling the anti-migraine effects of BIBN 4096 BS: a new calcitonin gene-related peptide receptor antagonist. Clin Pharmacokinet 45:715–728
Tvedskov JF, Lipka K, Ashina M et al (2005) No increase of calcitonin gene-related peptide in jugular blood during migraine. Ann Neurol 58:561–568
Verge VMK, Richardson PM, Wiesenfeld-Hallin Z et al (1995) Differential influence of nerve growth factor on neuropeptide expression in vivo: A novel role in peptide suppression in adult sensory neurons. J Neurosci 15:2081–2096
Wang Z, Ma W, Chabot J-G et al (2007) Involvement of calcitonin-gene related peptide in morphine analgesic tolerance by modulating astrocyte-derived interlukine-1 release. Soc Neurosci Abstr 922:10
Welch SP, Bass PP, Olson KG et al (1992) Morphine-induced modulation of calcitonin gene-related peptide levels. Pharmacol Biochem Behav 43:1107–1116
Wiesenfeld-Hallin Z, Hokfelt T, Lundberg JM et al (1984) Immunoreactive calcitonin gene-related peptide and substance P coexist in sensory neurons to the spinal cord and interact in spinal behavioral responses of the rat. Neurosci Lett 52:199–204
Woolf CJ, Wiesenfeld-Hallin Z (1986) Substance P and calcitonin gene-related peptide synergistically modulate the gain of the nociceptive flexor withdrawal reflex in the rat. Neurosci Lett 66:226–230
Xu P, Hall AK (2007) Activin acts with nerve growth factor to regulate calcitonin gene-related peptide mRNA in sensory neurons. Neuroscience 150:665–674
Xu P, Van Slambrouck C, Berti-Mattera L et al (2005) Activin induces tactile allodynia and increases calcitonin gene-related peptide after peripheral inflammation. J Neurosci 25:9227–9235
Yu LC, Hansson P, Lundeberg T (1994) The calcitonin gene-related peptide antagonist CGRP8-37 increases the latency to withdrawal responses in rats. Brain Res 653:223–230
Yu LC, Hansson P, Brodda-Jansen G et al (1996a) Intrathecal CGRP8-37-induced bilateral increase in hindpaw withdrawal latency in rats with unilateral inflammation. Br J Pharmacol 117:43–50
Yu LC, Hansson P, Lundeberg T (1996b) The calcitonin gene-related peptide antagonist CGRP(8-37) increases the latency to withdrawal responses bilaterally in rats with unilateral experimental mononeuropathy, an effect reversed by naloxone. Neuroscience 71:523–531
Zhang Z, Winborn CS, Marquez DP et al (2007) Sensitization of calcitonin gene-related peptide receptors by receptor activity-modifying protein-1 in the trigeminal ganglion. J Neurosci 27:2693–2703
Acknowledgements
This study was supported by grants from Canadian Institutes of Health Research to Remi Quirion.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media B.V
About this chapter
Cite this chapter
Ma, W., Chabot, JG., Schorscher-Petcu, A., Hong, Y., Wang, Z., Quirion, R. (2010). CGRP and Adrenomedullin as Pain-Related Peptides. In: Hay, D., Dickerson, I. (eds) The calcitonin gene-related peptide family. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2909-6_10
Download citation
DOI: https://doi.org/10.1007/978-90-481-2909-6_10
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-2908-9
Online ISBN: 978-90-481-2909-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)