The effect of intra-articular vanilloid receptor agonists on pain behavior measures in a murine model of acute monoarthritis

Abstract

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.

Use of Capsaicin to Treat Pain: Mechanistic and Therapeutic Considerations

“…This is similar to the situations in other deep tissues such as muscle or visceral organs [27,28,29]. Consistently, intraarticular injection of RTX or capsaicin improves weight-distribution behavior in carrageenan or MIA-induced arthritis in rats and mice [30,31,32]. Therefore, focal injection of capsaicin or RTX can be used to provide relief of mechanical hyperalgesia from deep tissues such as muscle or joints.…”

Electroacupuncture Reduces the Effects of Acute Noxious Stimulation on the Electrical Activity of Pain-Related Neurons in the Hippocampus of Control and Neuropathic Pain Rats

“…There are two kinds of pain: acute and chronic. Acute pain is very common in clinical practice, including pain in the perioperative setting [24], pain in patients with severe or concurrent medical illnesses (such as arthritis [25]), pain related to cancer or cancer treatment, and labor pain. Acute pain including neuropathic pain [26] affects bodily health and the quality of life.…”

Spontaneous and Evoked Measures of Pain in Murine Models of Monoarticular Knee Pain

“…We have developed methods for measuring spontaneous and evoked pain in three different models of murine arthritis that are sensitive and reproducible for measuring pain severity and the analgesic effects of intra-articular therapies 9,10 . We can also correlate pain relief with other histologic markers of pain and screen investigational drugs that would not be possible in humans.…”