The Antinociceptive Efficacy of HWTX-I Epidurally Administered in Rheumatoid Arthritis Rats

Abstract

Rheumatoid arthritis (RA) is one of the inflammatory kinds of arthritis in the clinical situation, and cytosolic Ca²⁺ overload has been proposed as one of the primary factors for many inflammatory cells activation, which lead to relative enzymes and inflammatory factors release. It is therefore accepted that Ca²⁺ channel blockers can protect joint injury from inflammation. In the present study we investigated the possible molecular mechanism of the antinociceptive efficacy of HWTX-I, a spider peptide toxin blocking Ca²⁺ channels, on the rat rheumatoid arthritis model. Our study demonstrates that HWTX-I can relieve pain in the inflammatory joints and eliminate arthrocele to some degree. Moreover, HWTX-I can also decrease the concentration of tumour necrosis factor α (TNF-α) and increase the concentration of interleukin 4(IL-4) and interleukin 10(IL-10) in rat’s serum. HWTX-I can also decrease the mRNA expression level of related factors of TNF-α, interleukin 1β (IL-1β) and interleukin 6(IL-6) in inflammatory pathways in rheumatoid arthritis. Therefore, the present results show that the epidural administration of HWTX-I is effective in antinociception in the rat model of rheumatoid arthritis, which may act through its inhibition on certain inflammatory pathways.

Key words

HWTX-I - rheumatoid arthritis - calcium channel blocker - antinociception

• References

• 1 Benslay DN, Bendele AM. Development of a rapid screen for detecting and differentiating immunomodulatory vs. anti-inflammatory compounds in rats. Agents Actions 1991; 34: 254-256
• 2 Binda MM, Molinas CR, Bastidas A, Koninckx PR. Effect of reactive oxygen species scavengers anti-inflammatory drugs and calcium-channel blockers on carbon dioxide pneumoperitoneum-enhanced adhesions in a laparoscopic mouse mode. Surg Endosc 2007; 21: 1826-1834
• 3 Chen BS, Xu YD, Zhong SQ. Establishment and evaluation of experimental animal model of CFA induced adjuvant arthritis in rats. Journal of Harbin Medical University 2005; 39: 489-491
• 4 Chen JQ, Zhang YQ, Liang SP. Antinociceptive effects of intrathecally administered huwentoxin-I, a selective N-type calcium channel blocker, in the formalin test in conscious rats. Toxicon 2005; 1: 15-20
• 5 Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001; 344: 907-916
• 6 Dayer JM. The process of identifying and understanding cytokines: from basic studies to treating rheumatic diseases. Best Pract Res Clin Rheumatol 2004; 18: 31-45
• 7 Devries GW, Mclaughlin A, Wenzel MB, Perez J, Harcourt D, Lee G. The anti-inflammatory activity of topically applied novel calcium channel antagonists. Inflammation 1995; 19: 261-275
• 8 Firestein GS. Evolving concepts of rheumatoid arthritis. Nature 2003; 423: 356-361
• 9 Frederick C, Hui L, Alastair M. Continuing postischemic neuronal death in CA1: influence of ischemia duration and cytoprotective doses of NBQX and SNX-111 in rats. Stroke 1999; 30: 662-668
• 10 Gao W, Lu J. Inflammatory cytokines and rheumatoid arthritis. China J Mod Med 2007; 17: 450-453
• 11 Harriss DJ, Atkinson G. Update - Ethical Standards in Sport and Exercise Science Research. Int J Sports Med 2011; 32: 819-821
• 12 Jacobson PB, Borgan SJ, Wilcox DM. A new spin on an old model: In vivo evaluation of disease progression by magnetic resonance imaging with respect to standard inflammatory parameters and histopathology in the adjuvant arthritic rat. Arthritis Rheum 1999; 42: 2060-2073
• 13 Kaklamanis PM. Experimental animal models resembling rheumatoid arthritis. Clin Rheumatol 1992; 11: 41-47
• 14 Lake BG, Lyubsky S. Dose dependent effect of continuous subcutaneous verapamil infusion on experimental acute pancreatitis in mice. Dig Dis Sci 1995; 40: 2349-2355
• 15 Leslie G, Ratkay AA, Zhang LW, Joseph TJ, Douglas W. Complete Freund’s adjuvant induces an earlier and more severe arthritis in MRL-ipr mice. J Immunol 1993; 9: 5081-5087
• 16 Liang SP. An overview of peptide toxins from the venom of the Chinese bird spider Selenocosmia huwena Wang. Toxicon 2004; 43: 575-585
• 17 Liang SP, Zhang DY, Pan X. Properties and amino acid sequence of Huwentoxin-1, a neurotoxin purified from the venom of the Chinese bird spider Ornithoctonus huwena. Toxicon 1993; 3: 969-978
• 18 Pearson CM. Development of arthritis periarthritis and periostitis in rats given adjuvants. Proc Soc Exp Biol Med 1956; 91: 95-100
• 19 Tintinger G, Steel HC, Anderson R. Taming the neutrophil calcium clearance and influx mechanisms as novel targets for pharmacological control. Clin Exp Immunol 2005; 141: 191-200
• 20 Van R, Royvan JL, Duits A, Lafeber FP, Bijlsma JW. Proinflammatory cytokine production and cartilage damage due to rheumatoid synovial T helper-1 activation is inhibited by interleukin-4. Ann Rheum Dis 1995; 54: 836-840
• 21 Van R, Royvan JL, Gmelig ML, Floris PJ, Lafeber G, Johannes W, Bijlsma J. Prevention and reversal of cartilage degradation in rheumatoid arthritis by interleukin-10 and interleukin-4. Arthritis Rheum 1996; 39: 829-835
• 22 Van SJ. Interleukin-6: an overview. Annu Rev Immunol 1990; 8: 253-278
• 23 Wang YR, Mao HF, Liu RY, Chen JQ. Effect of Huwentoxin-I on the TNF apoptosis pathway in hippocampus of rat with global cerebral ischemia. Chin J Sports Med 2007; 26: 571-574
• 24 Xiong W, Jin SW, Ye DY. The level of inflammation controlled by store operated Ca2+ channels. Chem Life 2006; 26: 35-38
• 25 Yaksh TL, Rudy TA. Chronic catheterization of the spinal subarachnoid space. Physiol Behav 1976; 17: 175-185