Rheumatoid arthritis (RA) is a chronic autoimmune arthritis that affects approximately 1% of the population. Synovial inflammation cannot fully explain the level of pain reported by patients and facilitation of pain processing at the spinal level has been implicated. We characterized the K/BxN serum transfer arthritis model as a model of joint inflammation-induced pain and examine pharmacologic responsiveness and spinal glia activation. Mechanical allodynia developed congruently with joint swelling. Surprisingly, allodynia persisted after resolution of inflammation. At the peak of joint inflammation, (days 4-10) hypersensitivity was attenuated with i.p. etanercept, gabapentin, and ketorolac. Following resolution of synovial inflammation (day 19-28), only gabapentin relieved allodynia. The superficial dorsal horn of arthritic mice displayed increased staining of microglia at early and late time points, but astrocyte staining increased only during the inflammatory phase. ATF3, a marker of nerve injury, was significantly increased in the lumbar dorsal root ganglia during the late phase (day 28). Hence, serum transfer in the K/BxN serum transfer arthritis model produces a persistent pain state, where the allodynia during the inflammatory state is attenuated by TNF and prostaglandin inhibitors, and the pharmacology and histochemistry data suggest a transition from an inflammatory state to a state that resembles a neuropathic condition over time. Therefore, the K/BxN serum transfer model represents a multifaceted model for studies exploring pain mechanisms in conditions of joint inflammation and may serve as a platform for exploring novel treatment strategies for pain in human arthritic conditions. K/BxN serum transfer arthritis produces persistent mechanical hypersensitivity despite resolution of clinical signs with evidence of transition from an inflammatory to neuropathic pain state.

It has been shown that pressure ulcer formation in critically ill paediatric patients increases morbidity and mortality. We sought to identify factors associated with pressure ulcer formation in paediatric patients on extracorporeal membrane oxygenation (ECMO). From December 2014 to 2015, we identified patients at our institution who developed a pressure ulcer to create two cohorts: ulcer and no ulcer. Variables of interest included: type of ECMO, ECMO indication, hours on ECMO, location of cannulas, volume of crystalloid and blood products received during the first 7 days or during the length of the ECMO run, albumin and lactate levels on the day of cannulation, and presence of vasopressor support or steroid therapy. Of 43 patients studied, 11 (25.5%) developed a pressure ulcer. Patients that developed ulcers were older (P = 0.001) and weighed more (P = 0.006). Femoral cannulation was more frequent in the ulcer group (36.4% vs 6.3%, P = 0.029), and duration of ECMO was longer (P = 0.007). Age, weight, duration of ECMO, and femoral cannulation may contribute to the development of pressure ulcers in children who require ECMO support. Further analysis is imperative to identify specific techniques and protocols that will prevent pressure ulcers in this critically ill population.