Korean J Physiol Pharmacol.  2016 Jan;20(1):129-136. 10.4196/kjpp.2016.20.1.129.

The effects of intra-articular resiniferatoxin on monosodium iodoacetate-induced osteoarthritic pain in rats

• Kim Y
• Kim EH
• Lee KS
• Lee K
• Park SH
• Na SH
• Ko C
• Kim J
• Yooon YW

• KMID: 2150482
• DOI: http://doi.org/10.4196/kjpp.2016.20.1.129

Abstract

This study was performed to investigate whether an intra-articular injection of transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX) would alleviate behavioral signs of arthritic pain in a rat model of osteoarthritis (OA). We also sought to determine the effect of RTX treatment on calcitonin gene-related peptide (CGRP) expression in the spinal cord. Knee joint inflammation was induced by intra-articular injection of monosodium iodoacetate (MIA, 8 mg/50 microl) and weight bearing percentage on right and left hindpaws during walking, paw withdrawal threshold to mechanical stimulation, and paw withdrawal latency to heat were measured to evaluate pain behavior. Intra-articular administration of RTX (0.03, 0.003 and 0.0003%) at 2 weeks after the induction of knee joint inflammation significantly improved reduction of weight bearing on the ipsilateral hindlimb and increased paw withdrawal sensitivity to mechanical and heat stimuli. The reduction of pain behavior persisted for 3~10 days according to each behavioral test. The MIA-induced increase in CGRP immunoreactivity in the spinal cord was decreased by RTX treatment in a dose-dependent manner. The present study demonstrated that a single intra-articular administration of RTX reduced pain behaviors for a relatively long time in an experimental model of OA and could normalize OA-associated changes in peptide expression in the spinal cord.

Keyword

Calcitonin gene-related peptide (CGRP); Joint pain; Monosodium iodoacetate (MIA); Osteoarthritis; Resiniferatoxin (RTX)

MeSH Terms

Animals
Arthralgia
Calcitonin Gene-Related Peptide
Hindlimb
Hot Temperature
Inflammation
Injections, Intra-Articular
Knee Joint
Models, Animal
Models, Theoretical
Osteoarthritis
Rats*
Spinal Cord
Walking
Weight-Bearing
Calcitonin Gene-Related Peptide

Figure

• 

  Fig. 1 Changes in knee joint diameter (A), weight bearing distribution (B) and paw withdrawal responses to mechanical (C) or thermal stimuli (D) in the ipsilateral side of the hind paw after 8 mg of intra-articular MIA injection.Asterisks indicate the values that were significantly different from the value obtained in the pre-MIA injection period (P, p<0.05). Data are expressed as mean±SEM.

• 

  Fig. 2 Effect of intra-articular resiniferatoxin on weight bearing measurement (A), paw withdrawal responses to mechanical (B) and thermal stimuli (C) in the ipsilateral side of the hind paw following MIA injection.RTX was administrated 14 days after MIA injection. Asterisks indicate the values that were significantly different from the value obtained pre-RTX injection period (P). Data are expressed as mean±SEM.

• 

  Fig. 3 (A) A representative section showing CGRP immunoreactivity in the dorsal horn of L3, L4 and L5 spinal cord.Transverse sections of the L3-L5 spinal cord segments were stained with anti-CGRP antibody in each group, scale bar: 200 µm. (B) Relative optical density of CGRP immunoreactivity in each group. Asterisks indicate the values that were significantly different between the RTX treated groups and MIA control group (p<0.05).

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