RESUMO
OBJECTIVE: Capsaicin (CAP) and Resiniferatoxin (RTX) are vanilloid receptor agonists that can normalize Evoked Pain Scores (EPS) and Automated Dynamic Weight Bearing (ADWB) measures in murine acute inflammatory arthritis when given by intra-articular (IA) injection. To determine whether these vanilloid receptor agonists have benefit in Complete Freund's Adjuvant (CFA) induced chronic inflammatory arthritis pain, we measured changes in ADWB and EPS in arthritic mice with and without treatment with IA CAP and RTX. METHODS AND MATERIALS: Chronic inflammatory arthritis was produced by IA injection of 30 µl of Complete Freund's Adjuvant (CFA) into the left knee of C57BL6 male mice 3 weeks prior to pain behavior testing. Mice were injected with either low or high dose IA RTX (10µl of 0.001 or 0.003%), or IA CAP (10 µL of 0.01%) 7 days prior to pain behavior testing. RESULTS: Chronic Inflammatory arthritis pain produced increased EPS and reduced ADWB measures for weight bearing in the affected limb of arthritic mice compared to naïve mice. ADWB measurements for time in CFA when compared with Naive were not significantly different, but suggested off-loading the arthritic limb to the normal limb. Treatment with IA CAP or RTX 7 days prior to pain behavior testing produced significant improvement in EPS but no improvement in ADWB measures. Neither IA CAP nor IA RTX had any impact on EPS or ADWB measurements in non-arthritic mice when given 7 days prior to pain behavioral testing. CONCLUSION: Using ADWB and EPS, we quantified pain in a murine chronic inflammatory arthritis model. IA CFA caused a significant increase in EPS and decreased ADWB measures in the affected limb. Treatment with IA RTX and CAP produced significant improvement in EPS in mice with mono-articular inflammatory arthritis. IA vanilloid treatment produced no improvement in ADWB measurements for weight and for time.
RESUMO
Arthritis is the most common cause of disability in the US, and the primary manifestation of arthritis is joint pain that leads to progressive physical limitation, disability, morbidity, and increased health care utilization. Capsaicin (CAP) is a vanilloid agonist that causes substance P depletion by interacting with vanilloid receptor transient receptor potential V1 on small unmyelinated C fibers. It has been used topically for analgesia in osteoarthritis with variable success. Resiniferatoxin (RTX) is an ultra potent CAP analog. The aim of this study was to measure the analgesic effects of intra-articular (IA) administration of CAP and RTX in experimental acute inflammatory arthritis in mice. Evoked pain score (EPS) and a dynamic weight bearing (DWB) device were used to measure nociceptive behaviors in a murine model of acute inflammatory monoarthritis. A total of 56 C57B16 male mice underwent EPS and DWB testing - 24 nonarthritic controls and 32 mice with carrageenan-induced arthritis. The effects of pretreatment with 0.1% CAP, 0.0003% RTX, or 0.001% RTX were measured. Nociception was reproducibly demonstrated by increased EPS and reduced DWB measures in the affected limb of arthritic mice. Pretreatment with 0.001% RTX resulted in statistically significant improvement in EPS and DWB measures when compared with those observed in carrageenan-induced arthritis animals. Pretreatment with IA 0.0003% RTX and IA 0.01% CAP resulted in improvement in some but not all of these measures. The remaining 24 mice underwent evaluation following treatment with 0.1% CAP, 0.0003% RTX, or 0.001% RTX, and the results obtained were similar to that of naïve, nonarthritic mice.
RESUMO
PURPOSE: Carrageenan-induced arthritis is a painful acute arthritis model that is simple to induce, with peak pain and inflammation occurring at about 3 hours. This arthritis model can be evaluated using semiquantitative evoked or non-evoked pain scoring systems. These measures are subjective and are often time- and labor-intensive. It would be beneficial to utilize quantitative, nonsubjective evaluations of pain with rapid assessment tools. We sought to compare the DigiGait™ and TreadScan™ systems and to validate the two gait analysis platforms for detection of carrageenan-induced monoarthritis pain and analgesic response through changes in gait behavior. METHODS: Non-arthritic mice and carrageenan-induced arthritic mice with and without analgesia were examined. A painful arthritic knee was produced by injection of 3% carrageenan into the knee joint of adult mice. Analgesic-treated mice were injected subcutaneously with 0.015 mg/mL (0.5 mg/kg) buprenorphine. Five-second videos were captured on the DigiGait™ or TreadScan™ system and, after calculating gait parameters, were compared using student's unpaired t-test. RESULTS: We found the DigiGait™ system consistently measured significantly longer stride measures (swing time, stance time, and stride time) than did TreadScan™. Both systems' measures of variability were equal. Reproducibility was inconsistent on both systems. While both systems detected alterations in some gait measures after carrageenan injection, none of the alterations were seen with both systems. Only the TreadScan™ detected normalization of gait measures after analgesia, but the system could not detect normalization across all measures that altered due to arthritis pain. Time spent on analysis was dependent on operator experience. CONCLUSION: Neither the DigiGait™ nor TreadScan™ system was useful for measuring changes in pain behaviors or analgesic responses in acute inflammatory monoarthritic mice.
