The nociceptin/orphanin FQ peptide receptor (NOP), activated by its endogenous peptide ligand nociceptin/orphanin FQ (N/OFQ), exerts several effects including modulation of pain signalling. We have examined, for the first time, the tissue distribution of the NOP receptor in clinical visceral and somatic pain disorders by immunohistochemistry and assessed functional effects of NOP and mu-opioid receptor activation in cultured human and rat dorsal root ganglion (DRG) neurons. Quantification of NOP-positive nerve fibres within the bladder suburothelium revealed a remarkable several-fold increase in detrusor overactivity (P<0.0001) and painful bladder syndrome patient specimens (P - 0.0014) compared with controls. In postmortem control human DRG, 75% to 80% of small/medium neurons (<= 50 mu m diameter) in the lumbar (somatic) and sacral (visceral) DRG were positive for NOP, and fewer large neurons; avulsion-injured cervical human DRG neurons showed similar numbers. NOP immunoreactivity was significantly decreased in injured peripheral nerves (P = 0.0004), and also in painful neuromas (P = 0.025). Calcium-imaging studies in cultured rat DRGneurons demonstrated dose-dependent inhibition of capsaicin responses in the presence of N/OFQ, with an IC50 of 8.6 pM. In cultured human DRG neurons, 32% inhibition of capsaicin responses was observed in the presence of 1 pM N/OFQ (P < 0.001). The maximum inhibition of capsaicin responses was greater with N/OFQ than mu-opioid receptor agonist DAMGO. Our findings highlight the potential of NOP agonists, particularly in urinary bladder overactivity and pain syndromes. The regulation of NOP expression in visceral and somatic sensory neurons by target-derived neurotrophic factors deserves further study, and the efficacy of NOP selective agonists in clinical trials.
机构:
INRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Rome, ItalyINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Agostini, Simona
;
Eutamene, Helene
论文数: 0引用数: 0
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机构:
INRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, FranceINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Eutamene, Helene
;
Broccardo, Maria
论文数: 0引用数: 0
h-index: 0
机构:
Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Rome, ItalyINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Broccardo, Maria
;
Improta, Giovanna
论文数: 0引用数: 0
h-index: 0
机构:
Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Rome, ItalyINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Improta, Giovanna
;
Petrella, Carla
论文数: 0引用数: 0
h-index: 0
机构:
Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Rome, ItalyINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Petrella, Carla
;
Theodorou, Vassillia
论文数: 0引用数: 0
h-index: 0
机构:
INRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, FranceINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Theodorou, Vassillia
;
Bueno, Lionel
论文数: 0引用数: 0
h-index: 0
机构:
INRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, FranceINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
机构:
Hammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
London Res Inst, Histopathol Unit, Canc Res UK, London WC2A 3PX, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Anand, U.
;
Otto, W. R.
论文数: 0引用数: 0
h-index: 0
机构:
London Res Inst, Histopathol Unit, Canc Res UK, London WC2A 3PX, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Otto, W. R.
;
Facer, P.
论文数: 0引用数: 0
h-index: 0
机构:
Hammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Facer, P.
;
Zebda, N.
论文数: 0引用数: 0
h-index: 0
机构:
Neurol & GI Ctr Excellence Drug Discovery, GlaxoSmithKiine, Harlow CM19 5AW, Essex, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Zebda, N.
;
Selmer, I.
论文数: 0引用数: 0
h-index: 0
机构:
Neurol & GI Ctr Excellence Drug Discovery, GlaxoSmithKiine, Harlow CM19 5AW, Essex, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Selmer, I.
;
Gunthorpe, M. J.
论文数: 0引用数: 0
h-index: 0
机构:
Neurol & GI Ctr Excellence Drug Discovery, GlaxoSmithKiine, Harlow CM19 5AW, Essex, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Gunthorpe, M. J.
;
Chessell, I. P.
论文数: 0引用数: 0
h-index: 0
机构:
Neurol & GI Ctr Excellence Drug Discovery, GlaxoSmithKiine, Harlow CM19 5AW, Essex, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Chessell, I. P.
;
Sinisi, M.
论文数: 0引用数: 0
h-index: 0
机构:
Royal Natl Orthopaed Hosp, Peripheral Nerve Injury Unit, Stanmore HA7 4LP, Middx, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Sinisi, M.
;
Birch, R.
论文数: 0引用数: 0
h-index: 0
机构:Hammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Birch, R.
;
Anand, P.
论文数: 0引用数: 0
h-index: 0
机构:
Hammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
机构:
Univ London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
London Res Inst, Canc Res UK, Histopathol Unit, London WC2A 3PX, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Anand, Uma
;
Otto, William R.
论文数: 0引用数: 0
h-index: 0
机构:
London Res Inst, Canc Res UK, Histopathol Unit, London WC2A 3PX, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Otto, William R.
;
Sanchez-Herrera, Daniel
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, Fac Med, Ctr Nanomed, London W12 0NN, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Sanchez-Herrera, Daniel
;
Facer, Paul
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Facer, Paul
;
Yiangou, Yiangos
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Yiangou, Yiangos
;
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机构:
Korchev, Yuri
;
Birch, Rolfe
论文数: 0引用数: 0
h-index: 0
机构:
Royal Natl Orthopaed Hosp, Peripheral Nerve Injury Unit, Stanmore H47 4LP, Middx, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Birch, Rolfe
;
Benham, Christopher
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline Inc, Neurol & GI Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Benham, Christopher
;
Bountra, Chas
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline Inc, Neurol & GI Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Bountra, Chas
;
Chessell, Iain P.
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline Inc, Neurol & GI Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Chessell, Iain P.
;
Anand, Praveen
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
机构:
London Res Inst, Histopathol Unit, London WC1A 3PX, EnglandLondon Res Inst, Histopathol Unit, London WC1A 3PX, England
Anand, Uma
;
Otto, William R.
论文数: 0引用数: 0
h-index: 0
机构:
London Res Inst, Histopathol Unit, London WC1A 3PX, EnglandLondon Res Inst, Histopathol Unit, London WC1A 3PX, England
Otto, William R.
;
Anand, Praveen
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, Peripheral Neuropathy Unit, Dept Clin Neurosci, London W12 0NN, EnglandLondon Res Inst, Histopathol Unit, London WC1A 3PX, England
机构:
INRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Rome, ItalyINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Agostini, Simona
;
Eutamene, Helene
论文数: 0引用数: 0
h-index: 0
机构:
INRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, FranceINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Eutamene, Helene
;
Broccardo, Maria
论文数: 0引用数: 0
h-index: 0
机构:
Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Rome, ItalyINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Broccardo, Maria
;
Improta, Giovanna
论文数: 0引用数: 0
h-index: 0
机构:
Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Rome, ItalyINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Improta, Giovanna
;
Petrella, Carla
论文数: 0引用数: 0
h-index: 0
机构:
Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Rome, ItalyINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Petrella, Carla
;
Theodorou, Vassillia
论文数: 0引用数: 0
h-index: 0
机构:
INRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, FranceINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
Theodorou, Vassillia
;
Bueno, Lionel
论文数: 0引用数: 0
h-index: 0
机构:
INRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, FranceINRA, UMR 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse 9, France
机构:
Hammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
London Res Inst, Histopathol Unit, Canc Res UK, London WC2A 3PX, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Anand, U.
;
Otto, W. R.
论文数: 0引用数: 0
h-index: 0
机构:
London Res Inst, Histopathol Unit, Canc Res UK, London WC2A 3PX, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Otto, W. R.
;
Facer, P.
论文数: 0引用数: 0
h-index: 0
机构:
Hammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Facer, P.
;
Zebda, N.
论文数: 0引用数: 0
h-index: 0
机构:
Neurol & GI Ctr Excellence Drug Discovery, GlaxoSmithKiine, Harlow CM19 5AW, Essex, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Zebda, N.
;
Selmer, I.
论文数: 0引用数: 0
h-index: 0
机构:
Neurol & GI Ctr Excellence Drug Discovery, GlaxoSmithKiine, Harlow CM19 5AW, Essex, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Selmer, I.
;
Gunthorpe, M. J.
论文数: 0引用数: 0
h-index: 0
机构:
Neurol & GI Ctr Excellence Drug Discovery, GlaxoSmithKiine, Harlow CM19 5AW, Essex, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Gunthorpe, M. J.
;
Chessell, I. P.
论文数: 0引用数: 0
h-index: 0
机构:
Neurol & GI Ctr Excellence Drug Discovery, GlaxoSmithKiine, Harlow CM19 5AW, Essex, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Chessell, I. P.
;
Sinisi, M.
论文数: 0引用数: 0
h-index: 0
机构:
Royal Natl Orthopaed Hosp, Peripheral Nerve Injury Unit, Stanmore HA7 4LP, Middx, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Sinisi, M.
;
Birch, R.
论文数: 0引用数: 0
h-index: 0
机构:Hammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
Birch, R.
;
Anand, P.
论文数: 0引用数: 0
h-index: 0
机构:
Hammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, EnglandHammersmith Hosp, Imperial Coll London, Peripheral Neuropathy Unit, London W12 0NN, England
机构:
Univ London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
London Res Inst, Canc Res UK, Histopathol Unit, London WC2A 3PX, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Anand, Uma
;
Otto, William R.
论文数: 0引用数: 0
h-index: 0
机构:
London Res Inst, Canc Res UK, Histopathol Unit, London WC2A 3PX, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Otto, William R.
;
Sanchez-Herrera, Daniel
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, Fac Med, Ctr Nanomed, London W12 0NN, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Sanchez-Herrera, Daniel
;
Facer, Paul
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Facer, Paul
;
Yiangou, Yiangos
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Yiangou, Yiangos
;
论文数: 引用数:
h-index:
机构:
Korchev, Yuri
;
Birch, Rolfe
论文数: 0引用数: 0
h-index: 0
机构:
Royal Natl Orthopaed Hosp, Peripheral Nerve Injury Unit, Stanmore H47 4LP, Middx, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Birch, Rolfe
;
Benham, Christopher
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline Inc, Neurol & GI Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Benham, Christopher
;
Bountra, Chas
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline Inc, Neurol & GI Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Bountra, Chas
;
Chessell, Iain P.
论文数: 0引用数: 0
h-index: 0
机构:
GlaxoSmithKline Inc, Neurol & GI Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
Chessell, Iain P.
;
Anand, Praveen
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, Peripheral Neuropathy Unit, London W12 0NN, England
机构:
London Res Inst, Histopathol Unit, London WC1A 3PX, EnglandLondon Res Inst, Histopathol Unit, London WC1A 3PX, England
Anand, Uma
;
Otto, William R.
论文数: 0引用数: 0
h-index: 0
机构:
London Res Inst, Histopathol Unit, London WC1A 3PX, EnglandLondon Res Inst, Histopathol Unit, London WC1A 3PX, England
Otto, William R.
;
Anand, Praveen
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, Peripheral Neuropathy Unit, Dept Clin Neurosci, London W12 0NN, EnglandLondon Res Inst, Histopathol Unit, London WC1A 3PX, England