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Published in: The Journal of Headache and Pain 4/2010

Open Access 01-08-2010 | Original

Cutaneous nociception and neurogenic inflammation evoked by PACAP38 and VIP

Authors: Henrik Winther Schytz, Helle Holst, Lars Arendt-Nielsen, Jes Olesen, Messoud Ashina

Published in: The Journal of Headache and Pain | Issue 4/2010

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Abstract

Pituitary adenylate cyclase-activating peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) belong to the same secretin–glucagon superfamily and are present in nerve fibers in dura and skin. Using a model of acute cutaneous pain we explored differences in pain perception and vasomotor responses between PACAP38 and VIP in 16 healthy volunteers in a double-blind, placebo-controlled, crossover study. All participants received intradermal injections of 200 pmol PACAP38, 200 pmol VIP and placebo into the volar forearm. Measurements included pain intensity on a visual analog scale (VAS), blood flow by laser Doppler flowmetry, visual flare and wheal. Pain intensities after PACAP38 and VIP were mild and limited to a short time of about 100 s after injection. The area under the VAS-time curve was larger following PACAP38 (P = 0.004) and VIP (P = 0.01) compared to placebo. We found no statistical difference in pain perception between PACAP38 and VIP. Skin blood flow increase, flare and wheal were larger after both PACAP38 (P = 0.011) and VIP (P = 0.001) compared to placebo. VIP induced a considerably larger increase in skin blood flow, flare and wheal than PACAP38 (P = 0.002). In conclusion, we found that peripheral nociceptive cutaneous responses elicited by PACAP38 and VIP are similar in healthy volunteers. This suggests that acute pain and vasomotor responses following intradermal injections of PACAP38 and VIP are primarily mediated by VPAC receptors.
Literature
1.
go back to reference Dickinson T, Fleetwood-Walker SM (1999) VIP and PACAP: very important in pain? Trends Pharmacol Sci 20:324–329, 10.1016/S0165-6147(99)01340-1, 1:CAS:528:DyaK1MXns1ymsLc%3D, 10431211CrossRefPubMed Dickinson T, Fleetwood-Walker SM (1999) VIP and PACAP: very important in pain? Trends Pharmacol Sci 20:324–329, 10.1016/S0165-6147(99)01340-1, 1:CAS:528:DyaK1MXns1ymsLc%3D, 10431211CrossRefPubMed
2.
go back to reference Dickson L, Aramori I, Sharkey J, Finlayson K (2006) VIP and PACAP receptor pharmacology: a comparison of intracellular signaling pathways. Ann N Y Acad Sci 1070:239–242, 10.1196/annals.1317.021, 1:CAS:528:DC%2BD28XpvVeht7w%3D, 16888173CrossRefPubMed Dickson L, Aramori I, Sharkey J, Finlayson K (2006) VIP and PACAP receptor pharmacology: a comparison of intracellular signaling pathways. Ann N Y Acad Sci 1070:239–242, 10.1196/annals.1317.021, 1:CAS:528:DC%2BD28XpvVeht7w%3D, 16888173CrossRefPubMed
3.
go back to reference Arimura A, Somogyvari-Vigh A, Miyata A, Mizuno K, Coy DH, Kitada C (1991) Tissue distribution of PACAP as determined by RIA: highly abundant in the rat brain and testes. Endocrinology 129:2787–2789, 10.1210/endo-129-5-2787, 1:CAS:528:DyaK3MXmsVyntbY%3D, 1935809CrossRefPubMed Arimura A, Somogyvari-Vigh A, Miyata A, Mizuno K, Coy DH, Kitada C (1991) Tissue distribution of PACAP as determined by RIA: highly abundant in the rat brain and testes. Endocrinology 129:2787–2789, 10.1210/endo-129-5-2787, 1:CAS:528:DyaK3MXmsVyntbY%3D, 1935809CrossRefPubMed
4.
go back to reference Ghatei MA, Takahashi K, Suzuki Y, Gardiner J, Jones PM, Bloom SR (1993) Distribution, molecular characterization of pituitary adenylate cyclase-activating polypeptide and its precursor encoding messenger RNA in human and rat tissues. J Endocrinol 136:159–166, 10.1677/joe.0.1360159, 1:CAS:528:DyaK3sXhs1Kitw%3D%3D, 8094091CrossRefPubMed Ghatei MA, Takahashi K, Suzuki Y, Gardiner J, Jones PM, Bloom SR (1993) Distribution, molecular characterization of pituitary adenylate cyclase-activating polypeptide and its precursor encoding messenger RNA in human and rat tissues. J Endocrinol 136:159–166, 10.1677/joe.0.1360159, 1:CAS:528:DyaK3sXhs1Kitw%3D%3D, 8094091CrossRefPubMed
5.
go back to reference Hannibal J, Mikkelsen JD, Clausen H, Holst JJ, Wulff BS, Fahrenkrug J (1995) Gene expression of pituitary adenylate cyclase activating polypeptide (PACAP) in the rat hypothalamus. Regul Pept 55:133–148, 10.1016/0167-0115(94)00099-J, 1:CAS:528:DyaK2MXjsFejt7w%3D, 7754101CrossRefPubMed Hannibal J, Mikkelsen JD, Clausen H, Holst JJ, Wulff BS, Fahrenkrug J (1995) Gene expression of pituitary adenylate cyclase activating polypeptide (PACAP) in the rat hypothalamus. Regul Pept 55:133–148, 10.1016/0167-0115(94)00099-J, 1:CAS:528:DyaK2MXjsFejt7w%3D, 7754101CrossRefPubMed
6.
go back to reference Mikkelsen JD, Hannibal J, Fahrenkrug J, Larsen PJ, Olcese J, McArdle C (1995) Pituitary adenylate cyclase activating peptide-38 (PACAP-38), PACAP-27, and PACAP related peptide (PRP) in the rat median eminence and pituitary. J Neuroendocrinol 7:47–55, 10.1111/j.1365-2826.1995.tb00666.x, 1:CAS:528:DyaK2MXjtFCktL8%3D, 7735297CrossRefPubMed Mikkelsen JD, Hannibal J, Fahrenkrug J, Larsen PJ, Olcese J, McArdle C (1995) Pituitary adenylate cyclase activating peptide-38 (PACAP-38), PACAP-27, and PACAP related peptide (PRP) in the rat median eminence and pituitary. J Neuroendocrinol 7:47–55, 10.1111/j.1365-2826.1995.tb00666.x, 1:CAS:528:DyaK2MXjtFCktL8%3D, 7735297CrossRefPubMed
7.
go back to reference Hansen JM, Sitarz J, Birk S, Rahmann AM, Oturai PS, Fahrenkrug J et al (2006) Vasoactive intestinal polypeptide evokes only a minimal headache in healthy volunteers. Cephalalgia 26:992–1003, 10.1111/j.1468-2982.2006.01149.x, 1:STN:280:DC%2BD28vmsVaitw%3D%3D, 16886936CrossRefPubMed Hansen JM, Sitarz J, Birk S, Rahmann AM, Oturai PS, Fahrenkrug J et al (2006) Vasoactive intestinal polypeptide evokes only a minimal headache in healthy volunteers. Cephalalgia 26:992–1003, 10.1111/j.1468-2982.2006.01149.x, 1:STN:280:DC%2BD28vmsVaitw%3D%3D, 16886936CrossRefPubMed
8.
go back to reference Rahmann A, Wienecke T, Hansen JM, Fahrenkrug J, Olesen J, Ashina M (2008) Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not induce migraine. Cephalalgia 28:226–236, 10.1111/j.1468-2982.2007.01497.x, 1:STN:280:DC%2BD1c%2Fpsl2gtA%3D%3D, 18254893CrossRefPubMed Rahmann A, Wienecke T, Hansen JM, Fahrenkrug J, Olesen J, Ashina M (2008) Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not induce migraine. Cephalalgia 28:226–236, 10.1111/j.1468-2982.2007.01497.x, 1:STN:280:DC%2BD1c%2Fpsl2gtA%3D%3D, 18254893CrossRefPubMed
9.
go back to reference Schytz HW, Birk S, Wienecke T, Kruuse C, Olesen J, Ashina M (2009) PACAP38 induces migraine-like attacks in patients with migraine without aura. Brain 132:16–25, 10.1093/brain/awn307, 19052139CrossRefPubMed Schytz HW, Birk S, Wienecke T, Kruuse C, Olesen J, Ashina M (2009) PACAP38 induces migraine-like attacks in patients with migraine without aura. Brain 132:16–25, 10.1093/brain/awn307, 19052139CrossRefPubMed
10.
go back to reference Roosterman D, Goerge T, Schneider SW, Bunnett NW, Steinhoff M (2006) Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev 86:1309–1379, 10.1152/physrev.00026.2005, 1:CAS:528:DC%2BD28Xht1SgtL3P, 17015491CrossRefPubMed Roosterman D, Goerge T, Schneider SW, Bunnett NW, Steinhoff M (2006) Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev 86:1309–1379, 10.1152/physrev.00026.2005, 1:CAS:528:DC%2BD28Xht1SgtL3P, 17015491CrossRefPubMed
11.
go back to reference Strassman AM, Levy D (2006) Response properties of dural nociceptors in relation to headache. J Neurophysiol 95:1298–1306, 10.1152/jn.01293.2005, 16492942CrossRefPubMed Strassman AM, Levy D (2006) Response properties of dural nociceptors in relation to headache. J Neurophysiol 95:1298–1306, 10.1152/jn.01293.2005, 16492942CrossRefPubMed
12.
go back to reference Schmelz M, Michael K, Weidner C, Schmidt R, Torebjork HE, Handwerker HO (2000) Which nerve fibers mediate the axon reflex flare in human skin? Neuroreport 11:645–648, 10.1097/00001756-200002280-00041, 1:STN:280:DC%2BD3c7otFamtQ%3D%3D, 10718329CrossRefPubMed Schmelz M, Michael K, Weidner C, Schmidt R, Torebjork HE, Handwerker HO (2000) Which nerve fibers mediate the axon reflex flare in human skin? Neuroreport 11:645–648, 10.1097/00001756-200002280-00041, 1:STN:280:DC%2BD3c7otFamtQ%3D%3D, 10718329CrossRefPubMed
13.
go back to reference Anand P, Bloom SR, McGregor GP (1983) Topical capsaicin pretreatment inhibits axon reflex vasodilatation caused by somatostatin and vasoactive intestinal polypeptide in human skin. Br J Pharmacol 78:665–669, 1:CAS:528:DyaL3sXktVSkur0%3D, 6133573PubMedCentralCrossRefPubMed Anand P, Bloom SR, McGregor GP (1983) Topical capsaicin pretreatment inhibits axon reflex vasodilatation caused by somatostatin and vasoactive intestinal polypeptide in human skin. Br J Pharmacol 78:665–669, 1:CAS:528:DyaL3sXktVSkur0%3D, 6133573PubMedCentralCrossRefPubMed
14.
go back to reference Raud J, Dahlen SE, Smedegard G, Hedqvist P (1989) An intravital microscopic model for mast cell-dependent inflammation in the hamster cheek pouch. Acta Physiol Scand 135:95–105, 10.1111/j.1748-1716.1989.tb08556.x, 1:STN:280:DyaL1M7mtlOrsw%3D%3D, 2493712CrossRefPubMed Raud J, Dahlen SE, Smedegard G, Hedqvist P (1989) An intravital microscopic model for mast cell-dependent inflammation in the hamster cheek pouch. Acta Physiol Scand 135:95–105, 10.1111/j.1748-1716.1989.tb08556.x, 1:STN:280:DyaL1M7mtlOrsw%3D%3D, 2493712CrossRefPubMed
15.
go back to reference Gazerani P, Andersen OK, Arendt-Nielsen L (2005) A human experimental capsaicin model for trigeminal sensitization. Gender-specific differences. Pain 118:155–163, 10.1016/j.pain.2005.08.009, 1:CAS:528:DC%2BD2MXhtFOmt7%2FL, 16202522CrossRefPubMed Gazerani P, Andersen OK, Arendt-Nielsen L (2005) A human experimental capsaicin model for trigeminal sensitization. Gender-specific differences. Pain 118:155–163, 10.1016/j.pain.2005.08.009, 1:CAS:528:DC%2BD2MXhtFOmt7%2FL, 16202522CrossRefPubMed
16.
go back to reference Fullerton A, Fischer T, Lahti A, Wilhelm KP, Takiwaki H, Serup J (1996) Guidelines for measurement of skin colour and erythema. A report from the Standardization Group of the European Society of Contact Dermatitis. Contact Dermatitis 35:1–10, 10.1111/j.1600-0536.1996.tb02258.x, 1:STN:280:DyaK2s%2Flt1eisA%3D%3D, 8896947CrossRefPubMed Fullerton A, Fischer T, Lahti A, Wilhelm KP, Takiwaki H, Serup J (1996) Guidelines for measurement of skin colour and erythema. A report from the Standardization Group of the European Society of Contact Dermatitis. Contact Dermatitis 35:1–10, 10.1111/j.1600-0536.1996.tb02258.x, 1:STN:280:DyaK2s%2Flt1eisA%3D%3D, 8896947CrossRefPubMed
17.
go back to reference Drewes AM, Helweg-Larsen S, Petersen P, Brennum J, Andreasen A, Poulsen LH, Jensen TS (1993) McGill Pain Questionnaire translated into Danish: experimental and clinical findings. Clin J Pain 9:80–87, 10.1097/00002508-199306000-00002, 1:STN:280:DyaK3szmsVSktQ%3D%3D, 8358143CrossRefPubMed Drewes AM, Helweg-Larsen S, Petersen P, Brennum J, Andreasen A, Poulsen LH, Jensen TS (1993) McGill Pain Questionnaire translated into Danish: experimental and clinical findings. Clin J Pain 9:80–87, 10.1097/00002508-199306000-00002, 1:STN:280:DyaK3szmsVSktQ%3D%3D, 8358143CrossRefPubMed
18.
go back to reference Van der Schueren BJ, de Hoon JN, Vanmolkot FH, Van Hecken A, Depre M, Kane SA et al (2007) Reproducibility of the capsaicin-induced dermal blood flow response as assessed by laser Doppler perfusion imaging. Br J Clin Pharmacol 64:580–590, 10.1111/j.1365-2125.2007.02939.x, 17578484, 1:CAS:528:DC%2BD2sXhtlOht7zIPubMedCentralCrossRefPubMed Van der Schueren BJ, de Hoon JN, Vanmolkot FH, Van Hecken A, Depre M, Kane SA et al (2007) Reproducibility of the capsaicin-induced dermal blood flow response as assessed by laser Doppler perfusion imaging. Br J Clin Pharmacol 64:580–590, 10.1111/j.1365-2125.2007.02939.x, 17578484, 1:CAS:528:DC%2BD2sXhtlOht7zIPubMedCentralCrossRefPubMed
19.
go back to reference Dalsgaard CJ, Rydh M, Haegerstrand A (1989) Cutaneous innervation in man visualized with protein gene product 9.5 (PGP 9.5) antibodies. Histochemistry 92:385–390, 10.1007/BF00492495, 1:STN:280:DyaK3c%2FmtFOksw%3D%3D, 2531128CrossRefPubMed Dalsgaard CJ, Rydh M, Haegerstrand A (1989) Cutaneous innervation in man visualized with protein gene product 9.5 (PGP 9.5) antibodies. Histochemistry 92:385–390, 10.1007/BF00492495, 1:STN:280:DyaK3c%2FmtFOksw%3D%3D, 2531128CrossRefPubMed
20.
go back to reference Schulze E, Witt M, Fink T, Hofer A, Funk RH (1997) Immunohistochemical detection of human skin nerve fibers. Acta Histochem 99:301–309, 1:CAS:528:DyaK2sXmtFSit7o%3D, 9381913CrossRefPubMed Schulze E, Witt M, Fink T, Hofer A, Funk RH (1997) Immunohistochemical detection of human skin nerve fibers. Acta Histochem 99:301–309, 1:CAS:528:DyaK2sXmtFSit7o%3D, 9381913CrossRefPubMed
21.
go back to reference Savage MV, Brengelmann GL, Buchan AM, Freund PR (1990) Cystic fibrosis, vasoactive intestinal polypeptide, and active cutaneous vasodilation. J Appl Physiol 69:2149–2154, 1:STN:280:DyaK3M7ntVSltw%3D%3D, 1706332PubMed Savage MV, Brengelmann GL, Buchan AM, Freund PR (1990) Cystic fibrosis, vasoactive intestinal polypeptide, and active cutaneous vasodilation. J Appl Physiol 69:2149–2154, 1:STN:280:DyaK3M7ntVSltw%3D%3D, 1706332PubMed
22.
go back to reference Groneberg DA, Welker P, Fischer TC, Dinh QT, Grutzkau A, Peiser C et al (2003) Down-regulation of vasoactive intestinal polypeptide receptor expression in atopic dermatitis. J Allergy Clin Immunol 111:1099–1105, 10.1067/mai.2003.1477, 1:CAS:528:DC%2BD3sXkt1Gltr0%3D, 12743576CrossRefPubMed Groneberg DA, Welker P, Fischer TC, Dinh QT, Grutzkau A, Peiser C et al (2003) Down-regulation of vasoactive intestinal polypeptide receptor expression in atopic dermatitis. J Allergy Clin Immunol 111:1099–1105, 10.1067/mai.2003.1477, 1:CAS:528:DC%2BD3sXkt1Gltr0%3D, 12743576CrossRefPubMed
23.
go back to reference Steinhoff M, McGregor GP, Radleff-Schlimme A, Steinhoff A, Jarry H, Schmidt WE (1999) Identification of pituitary adenylate cyclase activating polypeptide (PACAP) and PACAP type 1 receptor in human skin: expression of PACAP-38 is increased in patients with psoriasis. Regul Pept 80:49–55, 10.1016/S0167-0115(99)00010-5, 1:CAS:528:DyaK1MXitFans7k%3D, 10235634CrossRefPubMed Steinhoff M, McGregor GP, Radleff-Schlimme A, Steinhoff A, Jarry H, Schmidt WE (1999) Identification of pituitary adenylate cyclase activating polypeptide (PACAP) and PACAP type 1 receptor in human skin: expression of PACAP-38 is increased in patients with psoriasis. Regul Pept 80:49–55, 10.1016/S0167-0115(99)00010-5, 1:CAS:528:DyaK1MXitFans7k%3D, 10235634CrossRefPubMed
24.
go back to reference Odum L, Petersen LJ, Skov PS, Ebskov LB (1998) Pituitary adenylate cyclase activating polypeptide (PACAP) is localized in human dermal neurons and causes histamine release from skin mast cells. Inflamm Res 47:488–492, 10.1007/s000110050363, 1:STN:280:DyaK1M7gslSlsw%3D%3D, 9892043CrossRefPubMed Odum L, Petersen LJ, Skov PS, Ebskov LB (1998) Pituitary adenylate cyclase activating polypeptide (PACAP) is localized in human dermal neurons and causes histamine release from skin mast cells. Inflamm Res 47:488–492, 10.1007/s000110050363, 1:STN:280:DyaK1M7gslSlsw%3D%3D, 9892043CrossRefPubMed
25.
go back to reference Lundeberg L, Nordlind K (1999) Vasoactive intestinal polypeptide in allergic contact dermatitis: an immunohistochemical and radioimmunoassay study. Arch Dermatol Res 291:201–206, 10.1007/s004030050394, 1:CAS:528:DyaK1MXjtlKksr8%3D, 10335916CrossRefPubMed Lundeberg L, Nordlind K (1999) Vasoactive intestinal polypeptide in allergic contact dermatitis: an immunohistochemical and radioimmunoassay study. Arch Dermatol Res 291:201–206, 10.1007/s004030050394, 1:CAS:528:DyaK1MXjtlKksr8%3D, 10335916CrossRefPubMed
26.
go back to reference Fischer TC, Dinh QT, Peiser C, Loser C, Fischer A, Groneberg DA (2002) Simultaneous detection of receptor mRNA and ligand protein in human skin tissues. J Cutan Pathol 29:65–71, 10.1034/j.1600-0560.2002.290201.x, 12150135CrossRefPubMed Fischer TC, Dinh QT, Peiser C, Loser C, Fischer A, Groneberg DA (2002) Simultaneous detection of receptor mRNA and ligand protein in human skin tissues. J Cutan Pathol 29:65–71, 10.1034/j.1600-0560.2002.290201.x, 12150135CrossRefPubMed
27.
go back to reference Rukwied R, Heyer G (1999) Administration of acetylcholine and vasoactive intestinal polypeptide to atopic eczema patients. Exp Dermatol 8:39–45, 10.1111/j.1600-0625.1999.tb00346.x, 1:CAS:528:DyaK1MXpvVOqsA%3D%3D, 10206720CrossRefPubMed Rukwied R, Heyer G (1999) Administration of acetylcholine and vasoactive intestinal polypeptide to atopic eczema patients. Exp Dermatol 8:39–45, 10.1111/j.1600-0625.1999.tb00346.x, 1:CAS:528:DyaK1MXpvVOqsA%3D%3D, 10206720CrossRefPubMed
28.
go back to reference Jensen K, Tuxen C, Pedersen-Bjergaard U, Jansen I, Edvinsson L, Olesen J (1990) Pain, wheal and flare in human forearm skin induced by bradykinin and 5-hydroxytryptamine. Peptides 11:1133–1138, 10.1016/0196-9781(90)90142-R, 1:CAS:528:DyaK3MXhtFGmsbc%3D, 2087438CrossRefPubMed Jensen K, Tuxen C, Pedersen-Bjergaard U, Jansen I, Edvinsson L, Olesen J (1990) Pain, wheal and flare in human forearm skin induced by bradykinin and 5-hydroxytryptamine. Peptides 11:1133–1138, 10.1016/0196-9781(90)90142-R, 1:CAS:528:DyaK3MXhtFGmsbc%3D, 2087438CrossRefPubMed
29.
go back to reference Pedersen-Bjergaard U, Nielsen LB, Jensen K, Edvinsson L, Jansen I, Olesen J (1989) Algesia and local responses induced by neurokinin A and substance P in human skin and temporal muscle. Peptides 10:1147–1152, 10.1016/0196-9781(89)90006-5, 1:CAS:528:DyaK3cXkvV2jsw%3D%3D, 2482964CrossRefPubMed Pedersen-Bjergaard U, Nielsen LB, Jensen K, Edvinsson L, Jansen I, Olesen J (1989) Algesia and local responses induced by neurokinin A and substance P in human skin and temporal muscle. Peptides 10:1147–1152, 10.1016/0196-9781(89)90006-5, 1:CAS:528:DyaK3cXkvV2jsw%3D%3D, 2482964CrossRefPubMed
30.
go back to reference Pedersen-Bjergaard U, Nielsen LB, Jensen K, Edvinsson L, Jansen I, Olesen J (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, 10.1016/0196-9781(91)90022-H, 1:CAS:528:DyaK3MXit1WkurY%3D, 1712469CrossRefPubMed Pedersen-Bjergaard U, Nielsen LB, Jensen K, Edvinsson L, Jansen I, Olesen J (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, 10.1016/0196-9781(91)90022-H, 1:CAS:528:DyaK3MXit1WkurY%3D, 1712469CrossRefPubMed
31.
go back to reference Huttunen M, Harvima IT, Ackermann L, Harvima RJ, Naukkarinen A, Horsmanheimo M (1996) Neuropeptide- and capsaicin-induced histamine release in skin monitored with the microdialysis technique. Acta Derm Venereol 76:205–209, 1:STN:280:DyaK28zptlGhtQ%3D%3D, 8800300PubMed Huttunen M, Harvima IT, Ackermann L, Harvima RJ, Naukkarinen A, Horsmanheimo M (1996) Neuropeptide- and capsaicin-induced histamine release in skin monitored with the microdialysis technique. Acta Derm Venereol 76:205–209, 1:STN:280:DyaK28zptlGhtQ%3D%3D, 8800300PubMed
32.
go back to reference Brain SD, Tippins JR, Morris HR, MacIntyre I, Williams TJ (1986) Potent vasodilator activity of calcitonin gene-related peptide in human skin. J Invest Dermatol 87:533–536, 10.1111/1523-1747.ep12455620, 1:CAS:528:DyaL28XmtVels7k%3D, 2428885CrossRefPubMed Brain SD, Tippins JR, Morris HR, MacIntyre I, Williams TJ (1986) Potent vasodilator activity of calcitonin gene-related peptide in human skin. J Invest Dermatol 87:533–536, 10.1111/1523-1747.ep12455620, 1:CAS:528:DyaL28XmtVels7k%3D, 2428885CrossRefPubMed
33.
go back to reference Fjellner B, Hagermark O (1981) Studies on pruritogenic and histamine-releasing effects of some putative peptide neurotransmitters. Acta Derm Venereol 61:245–250, 1:CAS:528:DyaL3MXktVWjtrw%3D, 6167109PubMed Fjellner B, Hagermark O (1981) Studies on pruritogenic and histamine-releasing effects of some putative peptide neurotransmitters. Acta Derm Venereol 61:245–250, 1:CAS:528:DyaL3MXktVWjtrw%3D, 6167109PubMed
34.
go back to reference Sikand P, Shimada SG, Green BG, LaMotte RH (2009) Similar itch and nociceptive sensations evoked by punctate cutaneous application of capsaicin, histamine and cowhage. Pain 144:66–75, 10.1016/j.pain.2009.03.001, 1:CAS:528:DC%2BD1MXms1ygsrg%3D, 19423224PubMedCentralCrossRefPubMed Sikand P, Shimada SG, Green BG, LaMotte RH (2009) Similar itch and nociceptive sensations evoked by punctate cutaneous application of capsaicin, histamine and cowhage. Pain 144:66–75, 10.1016/j.pain.2009.03.001, 1:CAS:528:DC%2BD1MXms1ygsrg%3D, 19423224PubMedCentralCrossRefPubMed
35.
go back to reference Warren JB, Cockcroft JR, Larkin SW, Kajekar R, Macrae A, Ghatei MA, Bloom SR (1992) Pituitary adenylate cyclase activating polypeptide is a potent vasodilator in humans. J Cardiovasc Pharmacol 20:83–87, 1:CAS:528:DyaK38Xks1egtL0%3D, 1383635PubMed Warren JB, Cockcroft JR, Larkin SW, Kajekar R, Macrae A, Ghatei MA, Bloom SR (1992) Pituitary adenylate cyclase activating polypeptide is a potent vasodilator in humans. J Cardiovasc Pharmacol 20:83–87, 1:CAS:528:DyaK38Xks1egtL0%3D, 1383635PubMed
36.
go back to reference Hovell CJ, Beasley CR, Mani R, Holgate ST (1987) Laser Doppler flowmetry for determining changes in cutaneous blood flow following intradermal injection of histamine. Clin Allergy 17:469–479, 10.1111/j.1365-2222.1987.tb02041.x, 1:STN:280:DyaL1c%2FltlartQ%3D%3D, 2960474CrossRefPubMed Hovell CJ, Beasley CR, Mani R, Holgate ST (1987) Laser Doppler flowmetry for determining changes in cutaneous blood flow following intradermal injection of histamine. Clin Allergy 17:469–479, 10.1111/j.1365-2222.1987.tb02041.x, 1:STN:280:DyaL1c%2FltlartQ%3D%3D, 2960474CrossRefPubMed
37.
go back to reference Seebeck J, Kruse ML, Schmidt-Choudry A, Schmidt WE (1998) Pituitary adenylate cyclase activating polypeptide induces degranulation of rat peritoneal mast cells via high-affinity PACAP receptor-independent activation of G proteins. Ann N Y Acad Sci 865:141–146, 10.1111/j.1749-6632.1998.tb11172.x, 1:CAS:528:DyaK1MXmvFWmtg%3D%3D, 9928006CrossRefPubMed Seebeck J, Kruse ML, Schmidt-Choudry A, Schmidt WE (1998) Pituitary adenylate cyclase activating polypeptide induces degranulation of rat peritoneal mast cells via high-affinity PACAP receptor-independent activation of G proteins. Ann N Y Acad Sci 865:141–146, 10.1111/j.1749-6632.1998.tb11172.x, 1:CAS:528:DyaK1MXmvFWmtg%3D%3D, 9928006CrossRefPubMed
38.
go back to reference Burstein R, Yamamura H, Malick A, Strassman AM (1998) Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. J Neurophysiol 79:964–982, 1:STN:280:DyaK1c7jtVKluw%3D%3D, 9463456PubMed Burstein R, Yamamura H, Malick A, Strassman AM (1998) Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. J Neurophysiol 79:964–982, 1:STN:280:DyaK1c7jtVKluw%3D%3D, 9463456PubMed
39.
go back to reference Strassman AM, Raymond SA, Burstein R (1996) Sensitization of meningeal sensory neurons and the origin of headaches. Nature 384:560–564, 10.1038/384560a0, 1:CAS:528:DyaK2sXhtlWh, 8955268CrossRefPubMed Strassman AM, Raymond SA, Burstein R (1996) Sensitization of meningeal sensory neurons and the origin of headaches. Nature 384:560–564, 10.1038/384560a0, 1:CAS:528:DyaK2sXhtlWh, 8955268CrossRefPubMed
40.
go back to reference Gazerani P, Andersen OK, Arendt-Nielsen L (2007) Site-specific, dose-dependent, and sex-related responses to the experimental pain model induced by intradermal injection of capsaicin to the foreheads and forearms of healthy humans. J Orofac Pain 21:289–302, 18018990PubMed Gazerani P, Andersen OK, Arendt-Nielsen L (2007) Site-specific, dose-dependent, and sex-related responses to the experimental pain model induced by intradermal injection of capsaicin to the foreheads and forearms of healthy humans. J Orofac Pain 21:289–302, 18018990PubMed
41.
go back to reference Moskowitz MA (1993) Neurogenic inflammation in the pathophysiology and treatment of migraine. Neurology 43:S16–S20, 1:STN:280:DyaK3s3nsFGhsA%3D%3D, 8389008PubMed Moskowitz MA (1993) Neurogenic inflammation in the pathophysiology and treatment of migraine. Neurology 43:S16–S20, 1:STN:280:DyaK3s3nsFGhsA%3D%3D, 8389008PubMed
42.
go back to reference Levy D, Burstein R, Kainz V, Jakubowski M, Strassman AM (2007) Mast cell degranulation activates a pain pathway underlying migraine headache. Pain 130:166–176, 10.1016/j.pain.2007.03.012, 1:CAS:528:DC%2BD2sXmtVKisro%3D, 17459586PubMedCentralCrossRefPubMed Levy D, Burstein R, Kainz V, Jakubowski M, Strassman AM (2007) Mast cell degranulation activates a pain pathway underlying migraine headache. Pain 130:166–176, 10.1016/j.pain.2007.03.012, 1:CAS:528:DC%2BD2sXmtVKisro%3D, 17459586PubMedCentralCrossRefPubMed
43.
go back to reference Burstein R, Yarnitsky D, Goor-Aryeh I, Ransil BJ, Bajwa ZH (2000) An association between migraine and cutaneous allodynia. Ann Neurol 47:614–624, 10.1002/1531-8249(200005)47:5<614::AID-ANA9>3.0.CO;2-N, 1:STN:280:DC%2BD3c3mtlSrsA%3D%3D, 10805332CrossRefPubMed Burstein R, Yarnitsky D, Goor-Aryeh I, Ransil BJ, Bajwa ZH (2000) An association between migraine and cutaneous allodynia. Ann Neurol 47:614–624, 10.1002/1531-8249(200005)47:5<614::AID-ANA9>3.0.CO;2-N, 1:STN:280:DC%2BD3c3mtlSrsA%3D%3D, 10805332CrossRefPubMed
44.
go back to reference Wienecke T, Olesen J, Oturai PS, Ashina M (2009) Prostaglandin E2(PGE2) induces headache in healthy subjects. Cephalalgia 29:509–519, 10.1111/j.1468-2982.2008.01748.x, 1:STN:280:DC%2BD1M3oslamtg%3D%3D, 19187340CrossRefPubMed Wienecke T, Olesen J, Oturai PS, Ashina M (2009) Prostaglandin E2(PGE2) induces headache in healthy subjects. Cephalalgia 29:509–519, 10.1111/j.1468-2982.2008.01748.x, 1:STN:280:DC%2BD1M3oslamtg%3D%3D, 19187340CrossRefPubMed
45.
go back to reference Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J (2002) CGRP may play a causative role in migraine. Cephalalgia 22:54–61, 10.1046/j.1468-2982.2002.00310.x, 1:STN:280:DC%2BD383ltlGrtA%3D%3D, 11993614CrossRefPubMed Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J (2002) CGRP may play a causative role in migraine. Cephalalgia 22:54–61, 10.1046/j.1468-2982.2002.00310.x, 1:STN:280:DC%2BD383ltlGrtA%3D%3D, 11993614CrossRefPubMed
46.
go back to reference Lassen LH, Thomsen LL, Olesen J (1995) Histamine induces migraine via the H1-receptor. Support for the NO hypothesis of migraine. Neuroreport 6:1475–1479, 10.1097/00001756-199507310-00003, 1:CAS:528:DyaK2MXotlSmtbc%3D, 7579128CrossRefPubMed Lassen LH, Thomsen LL, Olesen J (1995) Histamine induces migraine via the H1-receptor. Support for the NO hypothesis of migraine. Neuroreport 6:1475–1479, 10.1097/00001756-199507310-00003, 1:CAS:528:DyaK2MXotlSmtbc%3D, 7579128CrossRefPubMed
47.
go back to reference Wienecke T, Olesen J, Oturai PS, Ashina M (2008) Prostacyclin (epoprostenol) induces headache in healthy subjects. Pain 139:106–116, 10.1016/j.pain.2008.03.018, 1:CAS:528:DC%2BD1cXhtFCgurzE, 18450380CrossRefPubMed Wienecke T, Olesen J, Oturai PS, Ashina M (2008) Prostacyclin (epoprostenol) induces headache in healthy subjects. Pain 139:106–116, 10.1016/j.pain.2008.03.018, 1:CAS:528:DC%2BD1cXhtFCgurzE, 18450380CrossRefPubMed
48.
go back to reference Schytz HW, Wienecke T, Olesen J, Ashina M (2009) Carbachol induces headache, but not migraine-like attacks, in migraine without aura patients. Cephalalgia (In press) Schytz HW, Wienecke T, Olesen J, Ashina M (2009) Carbachol induces headache, but not migraine-like attacks, in migraine without aura patients. Cephalalgia (In press)
49.
go back to reference Wienecke T, Olesen J, Ashina M (2009) Prostaglandin I2 (Epoprostenol) triggers migraine-like attacks in migraineurs. Cephalalgia (In Press) Wienecke T, Olesen J, Ashina M (2009) Prostaglandin I2 (Epoprostenol) triggers migraine-like attacks in migraineurs. Cephalalgia (In Press)
50.
go back to reference Levy D (2009) Migraine pain, meningeal inflammation, and mast cells. Curr Pain Headache Rep 13:237–240, 10.1007/s11916-009-0040-y, 19457286CrossRefPubMed Levy D (2009) Migraine pain, meningeal inflammation, and mast cells. Curr Pain Headache Rep 13:237–240, 10.1007/s11916-009-0040-y, 19457286CrossRefPubMed
51.
go back to reference Theoharides TC, Donelan J, Kandere-Grzybowska K, Konstantinidou A (2005) The role of mast cells in migraine pathophysiology. Brain Res Brain Res Rev 49:65–76, 10.1016/j.brainresrev.2004.11.006, 1:CAS:528:DC%2BD2MXlt1Ghu7g%3D, 15960987CrossRefPubMed Theoharides TC, Donelan J, Kandere-Grzybowska K, Konstantinidou A (2005) The role of mast cells in migraine pathophysiology. Brain Res Brain Res Rev 49:65–76, 10.1016/j.brainresrev.2004.11.006, 1:CAS:528:DC%2BD2MXlt1Ghu7g%3D, 15960987CrossRefPubMed
52.
go back to reference Ottosson A, Edvinsson L (1997) Release of histamine from dural mast cells by substance P and calcitonin gene-related peptide. Cephalalgia 17:166–174, 10.1046/j.1468-2982.1997.1703166.x, 1:STN:280:DyaK2szhtl2gug%3D%3D, 9170339CrossRefPubMed Ottosson A, Edvinsson L (1997) Release of histamine from dural mast cells by substance P and calcitonin gene-related peptide. Cephalalgia 17:166–174, 10.1046/j.1468-2982.1997.1703166.x, 1:STN:280:DyaK2szhtl2gug%3D%3D, 9170339CrossRefPubMed
Metadata
Title
Cutaneous nociception and neurogenic inflammation evoked by PACAP38 and VIP
Authors
Henrik Winther Schytz
Helle Holst
Lars Arendt-Nielsen
Jes Olesen
Messoud Ashina
Publication date
01-08-2010
Publisher
Springer Milan
Published in
The Journal of Headache and Pain / Issue 4/2010
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI
https://doi.org/10.1007/s10194-010-0214-3

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