nach oben

Inflammation Research

Erschienen in:

13.06.2017 | Original Research Paper

Anti-allodynic action of the disease-modifying anti-rheumatic drug iguratimod in a rat model of neuropathic pain

verfasst von: K. Morimoto, A. Miura, Keiichi Tanaka

Erschienen in: Inflammation Research | Ausgabe 10/2017

Einloggen, um Zugang zu erhalten

Abstract

Objective

Patients with rheumatoid arthritis experience nociceptive as well as neuropathic pain. The effect of iguratimod (IGU), a disease-modifying anti-rheumatic drug, on neuropathic pain in a rat model of chronic constriction injury (CCI) was examined in this study.

Methods

CCI was induced by making four ligations on the left sciatic nerve. Rats with stable signs of static allodynia were selected 2 weeks after the surgery and drug treatments were started (day 0). The test drugs were orally administered once daily for 15 days. The threshold of mechanical pain response in the hind paw was evaluated by the von Frey hair test in a blinded manner. To observe histological changes in the spinal cord, the L4 region was subjected to immunohistochemical analysis for the detection of microglial cells.

Results

IGU showed an anti-allodynic effect on CCI-induced neuropathic pain at days 6 and 14, but not at 90 min after the first administration of IGU. This effect of IGU was observed until day 21. Furthermore, IGU decreased the number of Iba-1-positive cells, which had been increased at the ipsilateral side of the dorsal horn by CCI.

Conclusions

These results suggest that IGU suppresses neuropathic pain via a different mechanism from that of current therapeutics.

Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569–81.CrossRefPubMed

Heiberg T, Finset A, Uhlig T, Kvien TK. Seven year changes in health status and priorities for improvement of health in patients with rheumatoid arthritis. Ann Rheum Dis. 2005;64:191–5.CrossRefPubMedPubMedCentral

Radner H, Neogi T, Smolen JS, Aletaha D. Performance of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: a systematic literature review. Ann Rheum Dis. 2014;73:114–23.CrossRefPubMed

Smolen JS, Landewé R, Breedveld FC, Buch M, Burmester G, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73:492–509.CrossRefPubMed

Smolen JS, Breedveld FC, Burmester GR, Bykerk V, Dougados M, Emery P, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75:3–15.CrossRefPubMed

Scott IC, Ibrahim F, Lewis CM, Scott DL, Strand V. Impact of intensive treatment and remission on health-related quality of life in early and established rheumatoid arthritis. RMD Open. 2016;2:e000270.CrossRefPubMedPubMedCentral

Lee YC, Cui J, Lu B, Frits ML, Iannaccone CK, Shadick NA, et al. Pain persists in DAS28 rheumatoid arthritis remission but not in ACR/EULAR remission: a longitudinal observational study. Arthritis Res Ther. 2011;13:R83.CrossRefPubMedPubMedCentral

Vermeer M, Kuper HH, van der Bijl AE, Baan H, Posthumus MD, Brus HL, et al. The provisional ACR/EULAR definition of remission in RA: a comment on the patient global assessment criterion. Rheumatology (Oxford). 2012;51:1076–80.CrossRef

Lee YC, Nassikas NJ, Clauw DJ. The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia. Arthritis Res Ther. 2011;13:211.CrossRefPubMedPubMedCentral

10.

Vladimirova N, Jespersen A, Bartels EM, Christensen AW, Bliddal H, Danneskiold-Samsøe B, et al. Pain sensitisation in women with active rheumatoid arthritis: a comparative cross-sectional study. Arthritis. 2015;2015:434109.CrossRefPubMedPubMedCentral

11.

Ahmed S, Magan T, Vargas M, Harrison A, Sofat N. Use of the painDETECT tool in rheumatoid arthritis suggests neuropathic and sensitization components in pain reporting. J Pain Res. 2014;7:579–88.PubMedPubMedCentral

12.

Ito S. Post anti-inflammatory treatment pain in rheumatoid arthritis patients. Mod Rheumatol Suppl. 2015;25:S357.

13.

Tanaka K, Yamaguchi T, Hara M. Iguratimod for the treatment of rheumatoid arthritis in Japan. Expert Rev Clin Immunol. 2015;11:565–73.CrossRefPubMed

14.

Hara M, Abe T, Sugawara S, Mizushima Y, Hoshi K, Irimajiri S, et al. Efficacy and safety of iguratimod compared with placebo and salazosulfapyridine in active rheumatoid arthritis: a controlled, multicenter, double-blind, parallel-group study. Mod Rheumatol. 2007;17:1–9.CrossRefPubMed

15.

Ishiguro N, Yamamoto K, Katayama K, Kondo M, Sumida T, Mimori T, et al. Concomitant iguratimod therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate: a randomized, double-blind, placebo-controlled trial. Mod Rheumatol. 2013;23:430–9.CrossRefPubMed

16.

Okamura K, Yonemoto Y, Okura C, Kobayashi T, Takagishi K. Efficacy of the clinical use of iguratimod therapy in patients with rheumatoid arthritis. Mod Rheumatol. 2015;25:235–40.CrossRefPubMed

17.

Tanaka K, Shimotori T, Makino S, Aikawa Y, Inaba T, Yoshida C, et al. Pharmacological studies of the new antiinflammatory agent 3-formylamino-7-methylsulfonylamino-6- phenoxy-4H-1-benzopyran-4-one, 1st communication, antiinflammatory, analgesic and other related properties. Arzneimittelforschung. 1992;42:935–44.PubMed

18.

Tanaka K, Shimotori T, Makino S, Eguchi M, Asaoka K, Kitamura R, et al. Pharmacological studies on 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1- benzopyran-4-one (T-614), 3rd communication, the involvement of bradykinin in its analgesic actions. J Pharmacobiodyn. 1992;15:641–7.CrossRefPubMed

19.

Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33:87–107.CrossRefPubMed

20.

Field MJ, Bramwell S, Hughes J, Singh L. Detection of static and dynamic components of mechanical allodynia in rat models of neuropathic pain: are they signalled by distinct primary sensory neurones? Pain. 1999;83:303–11.CrossRefPubMed

21.

Nakazato-Imasato E, Tanimoto-Mori S, Kurebayashi Y. Effect of mexiletine on dynamic allodynia induced by chronic constriction injury of the sciatic nerve in rats. J Vet Med Sci. 2009;71:991–4.CrossRefPubMed

22.

Swartjes M, Niesters M, Dahan A. Assessment of allodynia relief by tissue-protective molecules in a rat model of nerve injury-induced neuropathic pain. Methods Mol Biol. 2013;982:187–95.CrossRefPubMed

23.

Babcock AA, Kuziel WA, Rivest S, Owens T. Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS. J Neurosci. 2003;23:7922–30.PubMed

24.

Tanaka K, Kawasaki H, Kurata K, Aikawa Y, Tsukamoto Y, Inaba T. T-614, a novel antirheumatic drug, inhibits both of activity and induction of cyclooxygenase-2 (COX-2) in cultured fibroblasts. Jpn J Pharmacol. 1995;67:305–14.CrossRefPubMed

25.

Aikawa Y, Yamamoto M, Yamamoto T, Morimoto K, Tanaka K. An anti-rheumatic agent T-614 inhibits NF-κB activation in LPS- and TNF-α-stimulated THP-1 cells without interfering with IκBα degradation. Inflamm Res. 2002;51:188–94.CrossRefPubMed

26.

Kohno M, Aikawa Y, Tsubouchi Y, Hashiramoto A, Yamada R, Kawahito Y, et al. Inhibitory effect of T-614 on tumor necrosis factor-α induced cytokine production and nuclear factor-κB activation in cultured human synovial cells. J Rheumatol. 2001;28:2591–6.PubMed

27.

Luo Q, Sun Y, Liu W, Qian C, Jin B, Tao F, et al. A novel disease-modifying antirheumatic drug, iguratimod, ameliorates murine arthritis by blocking IL-17 signaling, distinct from methotrexate and leflunomide. J Immunol. 2013;191:4969–78.CrossRefPubMed

28.

Tanaka K, Yamamoto T, Aikawa Y, Kizawa K, Muramoto K, Matsuno H, et al. Inhibitory effects of an anti-rheumatic agent T-614 on immunoglobulin production by cultured B cells and rheumatoid synovial tissues engrafted into SCID mice. Rheumatology (Oxford). 2003;42:1365–71.CrossRef

29.

Tanaka K, Morimoto K. Therapeutic agent for disease based on inhibitory effect of macrophage migration inhibitory factor. Patent No. WO2014JP69026 20140717.

30.

Bloom J, Metz C, Nalawade S, Casabar J, Cheng KF, He M, et al. Identification of iguratimod as an inhibitor of macrophage migration inhibitory factor (MIF) with steroid-sparing potential. J Biol Chem. 2016;291:26502–14.CrossRefPubMed

31.

Ben-Menachem E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia. 2004;45:13–8.CrossRefPubMed

32.

Zhou T, Ding L, Li X, Zhang F, Zhang Q, Gong B, et al. Determination of iguratimod in rat plasma by high performance liquid chromatography: method and application. Biomed Chromatogr. 2008;22:260–4.CrossRefPubMed

33.

Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci. 2007;10:1361–8.CrossRefPubMed

34.

Milligan ED, Watkins LR. Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci. 2009;10:23–36.CrossRefPubMedPubMedCentral

35.

Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Physiology of microglia. Physiol Rev. 2011;91:461–553.CrossRefPubMed

36.

Dominguez E, Mauborgne A, Mallet J, Desclaux M, Pohl M. SOCS3-mediated blockade of JAK/STAT3 signaling pathway reveals its major contribution to spinal cord neuroinflammation and mechanical allodynia after peripheral nerve injury. J Neurosci. 2010;30:5754–66.CrossRefPubMed

37.

Wang F, Xu S, Shen X, Guo X, Peng Y, Yang J. Spinal macrophage migration inhibitory factor is a major contributor to rodent neuropathic pain-like hypersensitivity. Anesthesiology. 2011;114:643–59.CrossRefPubMed

38.

Alexander JK, Cox GM, Tian JB, Zha AM, Wei P, Kigerl KA, et al. Glucocorticoids and macrophage migration inhibitory factor (MIF) are neuroendocrine modulators of inflammation and neuropathic pain after spinal cord injury. Exp Neurol. 2012;236:351–62.CrossRefPubMedPubMedCentral

Titel: Anti-allodynic action of the disease-modifying anti-rheumatic drug iguratimod in a rat model of neuropathic pain
verfasst von: K. Morimoto
A. Miura
Keiichi Tanaka
Publikationsdatum: 13.06.2017
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 10/2017
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-017-1064-0

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

25.04.2024 | Hypotonie | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Anti-allodynic action of the disease-modifying anti-rheumatic drug iguratimod in a rat model of neuropathic pain

Abstract

Objective

Methods

Results

Conclusions

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Viel Bewegung in der Parkinsonforschung

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Innere Medizin

Springer Medizin

Abstract

Objective

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 10/2017

2K1C-activated Angiotensin II (Ang II) exacerbates vascular damage in a rat model of arthritis through the ATR/ERK1/2 signaling pathway

Delta neutrophil index (DNI) as a novel diagnostic and prognostic marker of infection: a systematic review and meta-analysis

Endocytosis is required for exocytosis and priming of respiratory burst activity in human neutrophils

Effects of sevoflurane on NF-кB and TNF-α expression in renal ischemia–reperfusion diabetic rats

Pam2CSK4 and Pam3CSK4 induce iNOS expression via TBK1 and MyD88 molecules in mouse macrophage cell line RAW264.7

Di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), an anticancer agent, exerts an anti-inflammatory effect in activated human mast cells

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Viel Bewegung in der Parkinsonforschung

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Innere Medizin