Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain

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Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain. / Nasser, A.; Bjerrum, Ole Jannik; Heegaard, A.-M.; Møller, Anette T.; Larsen, Majbritt; Dalbøge, Louise S.; Dupont, Erik; Jensen, Troels S.; Møller, Lisbeth B.

In: Molecular Pain, Vol. 9, 19.02.2013, p. 5.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Nasser, A, Bjerrum, OJ, Heegaard, A-M, Møller, AT, Larsen, M, Dalbøge, LS, Dupont, E, Jensen, TS & Møller, LB 2013, 'Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain', Molecular Pain, vol. 9, pp. 5. https://doi.org/10.1186/1744-8069-9-5

APA

Nasser, A., Bjerrum, O. J., Heegaard, A-M., Møller, A. T., Larsen, M., Dalbøge, L. S., ... Møller, L. B. (2013). Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain. Molecular Pain, 9, 5. https://doi.org/10.1186/1744-8069-9-5

Vancouver

Nasser A, Bjerrum OJ, Heegaard A-M, Møller AT, Larsen M, Dalbøge LS et al. Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain. Molecular Pain. 2013 Feb 19;9:5. https://doi.org/10.1186/1744-8069-9-5

Author

Nasser, A. ; Bjerrum, Ole Jannik ; Heegaard, A.-M. ; Møller, Anette T. ; Larsen, Majbritt ; Dalbøge, Louise S. ; Dupont, Erik ; Jensen, Troels S. ; Møller, Lisbeth B. / Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain. In: Molecular Pain. 2013 ; Vol. 9. pp. 5.

Bibtex

@article{551cb748b06e4a879606b308be453d25,
title = "Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain",
abstract = "Background: GTP cyclohydrolase 1 (GTP-CH1), the rate-limiting enzyme in the synthesis of tetrahydrobiopterin (BH4), encoded by the GCH1 gene, has been implicated in the development and maintenance of inflammatory pain in rats. In humans, homozygous carriers of a {"} pain-protective{"} (PP) haplotype of the GCH1 gene have been identified exhibiting lower pain sensitivity, but only following pain sensitisation. Ex vivo, the PP GCH1 haplotype is associated with decreased induction of GCH1 after stimulation, whereas the baseline BH4 production is not affected. Contrary, loss of function mutations in the GCH1 gene results in decreased basal GCH1 expression, and is associated with DOPA-responsive dystonia (DRD). So far it is unknown if such mutations affect acute and inflammatory pain.Results: In the current study, we examined the involvement of the GCH1 gene in pain models using the hyperphenylalaninemia 1 (hph-1) mouse, a genetic model for DRD, with only 10{\%} basal GTP-CH1 activity compared to wild type mice. The study included assays for determination of acute nociception as well as models for pain after sensitisation. Pain behavioural analysis of the hph-1 mice showed reduced pain-like responses following intraplantar injection of CFA, formalin and capsaicin; whereas decreased basal level of GTP-CH1 activity had no influence in na{\"i}ve hph-1 mice on acute mechanical and heat pain thresholds. Moreover, the hph-1 mice showed no signs of motor impairment or dystonia-like symptoms.Conclusions: In this study, we demonstrate novel evidence that genetic mutations in the GCH1 gene modulate pain-like hypersensitivity. Together, the present data suggest that BH4 is not important for basal heat and mechanical pain, but they support the hypothesis that BH4 plays a role in inflammation-induced hypersensitivity. Our studies suggest that the BH4 pathway could be a therapeutic target for the treatment of inflammatory pain conditions. Moreover, the hph-1 mice provide a valid model to study the consequence of congenital deficiency of GCH1 in painful conditions.",
author = "A. Nasser and Bjerrum, {Ole Jannik} and A.-M. Heegaard and M{\o}ller, {Anette T.} and Majbritt Larsen and Dalb{\o}ge, {Louise S.} and Erik Dupont and Jensen, {Troels S.} and M{\o}ller, {Lisbeth B.}",
year = "2013",
month = "2",
day = "19",
doi = "10.1186/1744-8069-9-5",
language = "English",
volume = "9",
pages = "5",
journal = "Molecular Pain",
issn = "1744-8069",
publisher = "BioMed Central",

}

RIS

TY - JOUR

T1 - Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain

AU - Nasser, A.

AU - Bjerrum, Ole Jannik

AU - Heegaard, A.-M.

AU - Møller, Anette T.

AU - Larsen, Majbritt

AU - Dalbøge, Louise S.

AU - Dupont, Erik

AU - Jensen, Troels S.

AU - Møller, Lisbeth B.

PY - 2013/2/19

Y1 - 2013/2/19

N2 - Background: GTP cyclohydrolase 1 (GTP-CH1), the rate-limiting enzyme in the synthesis of tetrahydrobiopterin (BH4), encoded by the GCH1 gene, has been implicated in the development and maintenance of inflammatory pain in rats. In humans, homozygous carriers of a " pain-protective" (PP) haplotype of the GCH1 gene have been identified exhibiting lower pain sensitivity, but only following pain sensitisation. Ex vivo, the PP GCH1 haplotype is associated with decreased induction of GCH1 after stimulation, whereas the baseline BH4 production is not affected. Contrary, loss of function mutations in the GCH1 gene results in decreased basal GCH1 expression, and is associated with DOPA-responsive dystonia (DRD). So far it is unknown if such mutations affect acute and inflammatory pain.Results: In the current study, we examined the involvement of the GCH1 gene in pain models using the hyperphenylalaninemia 1 (hph-1) mouse, a genetic model for DRD, with only 10% basal GTP-CH1 activity compared to wild type mice. The study included assays for determination of acute nociception as well as models for pain after sensitisation. Pain behavioural analysis of the hph-1 mice showed reduced pain-like responses following intraplantar injection of CFA, formalin and capsaicin; whereas decreased basal level of GTP-CH1 activity had no influence in naïve hph-1 mice on acute mechanical and heat pain thresholds. Moreover, the hph-1 mice showed no signs of motor impairment or dystonia-like symptoms.Conclusions: In this study, we demonstrate novel evidence that genetic mutations in the GCH1 gene modulate pain-like hypersensitivity. Together, the present data suggest that BH4 is not important for basal heat and mechanical pain, but they support the hypothesis that BH4 plays a role in inflammation-induced hypersensitivity. Our studies suggest that the BH4 pathway could be a therapeutic target for the treatment of inflammatory pain conditions. Moreover, the hph-1 mice provide a valid model to study the consequence of congenital deficiency of GCH1 in painful conditions.

AB - Background: GTP cyclohydrolase 1 (GTP-CH1), the rate-limiting enzyme in the synthesis of tetrahydrobiopterin (BH4), encoded by the GCH1 gene, has been implicated in the development and maintenance of inflammatory pain in rats. In humans, homozygous carriers of a " pain-protective" (PP) haplotype of the GCH1 gene have been identified exhibiting lower pain sensitivity, but only following pain sensitisation. Ex vivo, the PP GCH1 haplotype is associated with decreased induction of GCH1 after stimulation, whereas the baseline BH4 production is not affected. Contrary, loss of function mutations in the GCH1 gene results in decreased basal GCH1 expression, and is associated with DOPA-responsive dystonia (DRD). So far it is unknown if such mutations affect acute and inflammatory pain.Results: In the current study, we examined the involvement of the GCH1 gene in pain models using the hyperphenylalaninemia 1 (hph-1) mouse, a genetic model for DRD, with only 10% basal GTP-CH1 activity compared to wild type mice. The study included assays for determination of acute nociception as well as models for pain after sensitisation. Pain behavioural analysis of the hph-1 mice showed reduced pain-like responses following intraplantar injection of CFA, formalin and capsaicin; whereas decreased basal level of GTP-CH1 activity had no influence in naïve hph-1 mice on acute mechanical and heat pain thresholds. Moreover, the hph-1 mice showed no signs of motor impairment or dystonia-like symptoms.Conclusions: In this study, we demonstrate novel evidence that genetic mutations in the GCH1 gene modulate pain-like hypersensitivity. Together, the present data suggest that BH4 is not important for basal heat and mechanical pain, but they support the hypothesis that BH4 plays a role in inflammation-induced hypersensitivity. Our studies suggest that the BH4 pathway could be a therapeutic target for the treatment of inflammatory pain conditions. Moreover, the hph-1 mice provide a valid model to study the consequence of congenital deficiency of GCH1 in painful conditions.

UR - http://www.scopus.com/inward/record.url?scp=84873954449&partnerID=8YFLogxK

U2 - 10.1186/1744-8069-9-5

DO - 10.1186/1744-8069-9-5

M3 - Journal article

C2 - 23421753

AN - SCOPUS:84873954449

VL - 9

SP - 5

JO - Molecular Pain

JF - Molecular Pain

SN - 1744-8069

ER -

ID: 45587686