Antiinflammatory and Analgesic Effects of Somatostatin Released from Capsaicin-Sensitive Sensory Nerve Terminals in a Freund's Adjuvant-Induced Chronic Arthritis Model in the Rat

Z. Helyes, Árpád Szabó, J. Németh, Balázs Jakab, E. Pintér, Ágnes Bánvölgyi, L. Kereskai, G. Kéri, J. Szolcsányi

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Abstract

Objective. We previously demonstrated that somatostatin (SOM) released from the activated peripheral terminals of capsaicin-sensitive primary sensory neurons inhibits acute inflammation and nociception. This study was undertaken to examine this systemic "sensocrine" function of neuronally derived somatostatin in chronic inflammation in the Freund's complete adjuvant (CFA)-induced arthritis model. Methods. Arthritis of the tibiotarsal joint of Lewis rats was evoked by subcutaneous injection of CFA into the left hind paw and the tail root. For 3 weeks, the volume of the paws was measured by plethysmometry, and the mechanonociceptive thresholds were measured by esthesiometry. Plasma concentrations of SOM were determined by radioimmunoassay, and histologic studies of the joints were performed. To impair the function of capsaicin-sensitive afferents, the capsaicin receptor (VR1/TRPV1) agonist resiniferatoxin (RTX) was injected subcutaneously (30, 70, and 100 μg/kg on 3 subsequent days) 7 days before CFA administration. The SOM receptor antagonist cyclosomatostatin (c-SOM; 20 μg/kg) or, in another group, the synthetic heptapeptide agonist TT-232 (2 × 50-400 μg/kg) was administered intraperitoneally every day. Results. RTX pretreatment or c-SOM injection significantly increased edema and mechanical hyperalgesia of both CFA-treated and contralateral paws. The histologic score based on synovial thickening, cell infiltration, cartilage destruction, and bone erosion was also significantly higher both in the RTX- and the c-SOM-injected groups. These parameters were dose-dependently decreased by TT-232. Plasma SOM-like immunoreactivity increased 4-fold on the twenty-first day, and was inhibited by RTX pretreatment, as well as by daily administration of TT-232. Conclusion. Our data suggest that SOM released into the circulation from capsaicin-sensitive afferents in response to prolonged activation exerts systemic antiinflammatory and analgesic effects. TT-232 can open new perspectives in the treatment of chronic arthritis.

Original languageEnglish
Pages (from-to)1677-1685
Number of pages9
JournalArthritis and Rheumatism
Volume50
Issue number5
DOIs
Publication statusPublished - May 2004

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Experimental Arthritis
Freund's Adjuvant
Capsaicin
Somatostatin
Analgesics
Anti-Inflammatory Agents
Arthritis
Joints
Inflammation
TRPV Cation Channels
Somatostatin Receptors
Nociception
Synovitis
Hyperalgesia
Sensory Receptor Cells
Subcutaneous Injections
Cartilage
Radioimmunoassay
Tail
Edema

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

@article{e70da3410c804afd8acc9df35f33ea48,
title = "Antiinflammatory and Analgesic Effects of Somatostatin Released from Capsaicin-Sensitive Sensory Nerve Terminals in a Freund's Adjuvant-Induced Chronic Arthritis Model in the Rat",
abstract = "Objective. We previously demonstrated that somatostatin (SOM) released from the activated peripheral terminals of capsaicin-sensitive primary sensory neurons inhibits acute inflammation and nociception. This study was undertaken to examine this systemic {"}sensocrine{"} function of neuronally derived somatostatin in chronic inflammation in the Freund's complete adjuvant (CFA)-induced arthritis model. Methods. Arthritis of the tibiotarsal joint of Lewis rats was evoked by subcutaneous injection of CFA into the left hind paw and the tail root. For 3 weeks, the volume of the paws was measured by plethysmometry, and the mechanonociceptive thresholds were measured by esthesiometry. Plasma concentrations of SOM were determined by radioimmunoassay, and histologic studies of the joints were performed. To impair the function of capsaicin-sensitive afferents, the capsaicin receptor (VR1/TRPV1) agonist resiniferatoxin (RTX) was injected subcutaneously (30, 70, and 100 μg/kg on 3 subsequent days) 7 days before CFA administration. The SOM receptor antagonist cyclosomatostatin (c-SOM; 20 μg/kg) or, in another group, the synthetic heptapeptide agonist TT-232 (2 × 50-400 μg/kg) was administered intraperitoneally every day. Results. RTX pretreatment or c-SOM injection significantly increased edema and mechanical hyperalgesia of both CFA-treated and contralateral paws. The histologic score based on synovial thickening, cell infiltration, cartilage destruction, and bone erosion was also significantly higher both in the RTX- and the c-SOM-injected groups. These parameters were dose-dependently decreased by TT-232. Plasma SOM-like immunoreactivity increased 4-fold on the twenty-first day, and was inhibited by RTX pretreatment, as well as by daily administration of TT-232. Conclusion. Our data suggest that SOM released into the circulation from capsaicin-sensitive afferents in response to prolonged activation exerts systemic antiinflammatory and analgesic effects. TT-232 can open new perspectives in the treatment of chronic arthritis.",
author = "Z. Helyes and {\'A}rp{\'a}d Szab{\'o} and J. N{\'e}meth and Bal{\'a}zs Jakab and E. Pint{\'e}r and {\'A}gnes B{\'a}nv{\"o}lgyi and L. Kereskai and G. K{\'e}ri and J. Szolcs{\'a}nyi",
year = "2004",
month = "5",
doi = "10.1002/art.20184",
language = "English",
volume = "50",
pages = "1677--1685",
journal = "Arthritis and Rheumatology",
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TY - JOUR

T1 - Antiinflammatory and Analgesic Effects of Somatostatin Released from Capsaicin-Sensitive Sensory Nerve Terminals in a Freund's Adjuvant-Induced Chronic Arthritis Model in the Rat

AU - Helyes, Z.

AU - Szabó, Árpád

AU - Németh, J.

AU - Jakab, Balázs

AU - Pintér, E.

AU - Bánvölgyi, Ágnes

AU - Kereskai, L.

AU - Kéri, G.

AU - Szolcsányi, J.

PY - 2004/5

Y1 - 2004/5

N2 - Objective. We previously demonstrated that somatostatin (SOM) released from the activated peripheral terminals of capsaicin-sensitive primary sensory neurons inhibits acute inflammation and nociception. This study was undertaken to examine this systemic "sensocrine" function of neuronally derived somatostatin in chronic inflammation in the Freund's complete adjuvant (CFA)-induced arthritis model. Methods. Arthritis of the tibiotarsal joint of Lewis rats was evoked by subcutaneous injection of CFA into the left hind paw and the tail root. For 3 weeks, the volume of the paws was measured by plethysmometry, and the mechanonociceptive thresholds were measured by esthesiometry. Plasma concentrations of SOM were determined by radioimmunoassay, and histologic studies of the joints were performed. To impair the function of capsaicin-sensitive afferents, the capsaicin receptor (VR1/TRPV1) agonist resiniferatoxin (RTX) was injected subcutaneously (30, 70, and 100 μg/kg on 3 subsequent days) 7 days before CFA administration. The SOM receptor antagonist cyclosomatostatin (c-SOM; 20 μg/kg) or, in another group, the synthetic heptapeptide agonist TT-232 (2 × 50-400 μg/kg) was administered intraperitoneally every day. Results. RTX pretreatment or c-SOM injection significantly increased edema and mechanical hyperalgesia of both CFA-treated and contralateral paws. The histologic score based on synovial thickening, cell infiltration, cartilage destruction, and bone erosion was also significantly higher both in the RTX- and the c-SOM-injected groups. These parameters were dose-dependently decreased by TT-232. Plasma SOM-like immunoreactivity increased 4-fold on the twenty-first day, and was inhibited by RTX pretreatment, as well as by daily administration of TT-232. Conclusion. Our data suggest that SOM released into the circulation from capsaicin-sensitive afferents in response to prolonged activation exerts systemic antiinflammatory and analgesic effects. TT-232 can open new perspectives in the treatment of chronic arthritis.

AB - Objective. We previously demonstrated that somatostatin (SOM) released from the activated peripheral terminals of capsaicin-sensitive primary sensory neurons inhibits acute inflammation and nociception. This study was undertaken to examine this systemic "sensocrine" function of neuronally derived somatostatin in chronic inflammation in the Freund's complete adjuvant (CFA)-induced arthritis model. Methods. Arthritis of the tibiotarsal joint of Lewis rats was evoked by subcutaneous injection of CFA into the left hind paw and the tail root. For 3 weeks, the volume of the paws was measured by plethysmometry, and the mechanonociceptive thresholds were measured by esthesiometry. Plasma concentrations of SOM were determined by radioimmunoassay, and histologic studies of the joints were performed. To impair the function of capsaicin-sensitive afferents, the capsaicin receptor (VR1/TRPV1) agonist resiniferatoxin (RTX) was injected subcutaneously (30, 70, and 100 μg/kg on 3 subsequent days) 7 days before CFA administration. The SOM receptor antagonist cyclosomatostatin (c-SOM; 20 μg/kg) or, in another group, the synthetic heptapeptide agonist TT-232 (2 × 50-400 μg/kg) was administered intraperitoneally every day. Results. RTX pretreatment or c-SOM injection significantly increased edema and mechanical hyperalgesia of both CFA-treated and contralateral paws. The histologic score based on synovial thickening, cell infiltration, cartilage destruction, and bone erosion was also significantly higher both in the RTX- and the c-SOM-injected groups. These parameters were dose-dependently decreased by TT-232. Plasma SOM-like immunoreactivity increased 4-fold on the twenty-first day, and was inhibited by RTX pretreatment, as well as by daily administration of TT-232. Conclusion. Our data suggest that SOM released into the circulation from capsaicin-sensitive afferents in response to prolonged activation exerts systemic antiinflammatory and analgesic effects. TT-232 can open new perspectives in the treatment of chronic arthritis.

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