(258) Reversal of Mechanical Hyperalgesia by a Dual-Acting, Peripherally-Restricted Kappa/Delta Opioid Agonist (CA1001) in a Rat Model of Inflammatory Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory pain condition. In RA and other inflammatory states, normally sequestersed peripheral delta- opioid receptors may become active, allowing  delta -opioid agonists to participate in the pain pathway directly and through allosteric modulation of peripheral  kappa- opioid receptors. This study evaluated the efficacy of a single intraperitoneal injection of CA1001 (a novel dual-acting, peripherally restricted kappa/delta opioid agonist) on hyperalgesic nociceptive behaviors in the CFA (Complete Freundu0027s Adjuvant) Model of Inflammatory Arthritis Pain in Rats. Following IACUC approval, inflammatory arthritis pain was induced with injection of 50 μL CFA into the tibio-tarsal joint. Mechanical hyperalgesia was assessed via joint compression thresholds (JCTs). 50 animals were randomly assigned to 5 groups (Power: 80%). Ipsilateral and contralateral joint compression thresholds (JCTs) were assessed prior to CFA injection, pre-dosing on Day 0, and 1, 2, and 4 hours post-dosing. Animals were administered a single dose of vehicle, CA1001 (1, 5, or 10 mg/kg IP), or celecoxib (30 mg/kg PO: active control; internal validity) on day 0 (14 days after CFA). All behavioral evaluations were performed by a blinded observer. Mechanical hyperalgesia was measured using a digital Randall-Selitto device. CA1001 (10 mg/kg) significantly increased paw compression thresholds compared to vehicle at all time points, (p