Search

Objective: To investigate the specific effect of insomnia on neuropsychological functioning in patients with very complex chronic pain. Background: Individuals with insomnia disorder or chronic pain often experience cognitive deficits, with both conditions appearing to correlate with impairments in neuropsychological functions. As insomnia often occurs comorbid with chronic pain, distinguishing the differential effects of these two syndromes on an individual's neuropsychological functioning can be challenging. Comorbid depressive symptoms in these individuals, which may also affect cognitive function, may further obscure the associations between chronic pain, insomnia, and the neuropsychological profile. Methods: The neuropsychological function of 22 individuals with very complex chronic pain was assessed using specialized tests examining aspects of memory and executive functioning. The severity of insomnia, depression, and anxiety was measured using questionnaires, and pain levels were assessed using a visual analog scale. Pain medications were transformed to the morphine-equivalent daily dose. Results: Insomnia severity was found to predict memory function, accounting for 32.4% of the variance: A 1 SD increase in insomnia severity decreased memory function by 0.57 SD. The negative correlation between insomnia and memory was significant even after controlling for pain level, morphine-equivalent daily dose, and comorbid levels of anxiety and depression. Conclusions: Insomnia severity independently predicted memory function in patients with very complex chronic pain, even after controlling for other factors known to impair cognitive function. Insomnia may possibly explain some of the cognitive impairments related to chronic pain; thus, screening for, and treating, sleep disturbances may be a central aspect of chronic pain rehabilitation. more...

Background: Ketorolac is an effective non-steroidal anti-inflammatory drug, commonly used with local anaesthetics as part of local infiltration analgesia protocols following orthopaedic surgery. However, systemic uptake and drug action may be the major mechanism after local infiltration. The aims of this project were to study the effects of a small, systemically ineffective dose of ketorolac given intra-articularly for post-operative pain and also to study synovial inflammatory biomarkers. We investigated whether ketorolac affects pro-inflammatory biomarkers in an invitro model, as well. Methods: In this placebo-controlled, blind, randomized study, we analysed intra-articular ketorolac (5mg) in ambulatory minor knee surgery patients with moderate or severe pain (n=44). We assessed post-operative pain intensity (n=44) and analysed microdialysis samples taken from knee synovial tissue every 20min (n=34). We also tested cyclooxygenase-independent effects of ketorolac in synovial cells stimulated by prostaglandin E-2 and chondroitin sulphate invitro. Results: Intra-articular ketorolac (5mg) administration did not reduce pain or synovial pro-inflammatory cytokines CXCL1, IL-8, and MCP-1, 0-120min after knee arthroscopy. Female gender was a risk factor for moderate or severe pain (relative risk 1.45, 95% confidence interval 1.04-2.01). Paradoxically, ketorolac increased the release of CXCL1 and IL-8 in prostaglandin E-2 and chondroitin sulphate-stimulated synovial cells invitro. Conclusion: Ketorolac prescribed at a low dose intra-articularly does not produce any detectable analgesic effect after minor knee surgery. more...

Aims: D-Deprenyl when used as a positron emission tomography tracer visualizes peripheral inflammation. The major aim of the current study was to identify and investigate the properties of the binding target for D-deprenyl in synovial membrane explants from arthritic patients. Main methods: Thirty patients diagnosed with arthritis or osteoarthritis were enrolled into the study. Homologous and competitive radioligand binding assays utilizing [H-3]D-deprenyl were performed to investigate the biochemical characteristics of the binding site and assess differences in the binding profile in synovial membranes exhibiting varying levels of inflammation. Key findings: The [H-3]D-deprenyl binding assay confirmed the existence of a single, saturable population of membrane-bound protein binding sites in synovial membrane homogenates. The macroscopically determined level of inflammation correlated with an increase in [H-3]D-deprenyl binding affinity, without significant alterations in binding site density. Selective monoamine oxidase B inhibitor, selegiline competed for the same site as [H-3]D-deprenyl, but failed to differentiate the samples with regard to their inflammation grade. A monoamine oxidase A inhibitor, pirlindole mesylate showed only weak displacement of [H-3]D-deprenyl binding. No significant alterations in monoamine oxidase B expression was detected, thus it was not confirmed whether it could serve as a marker for ongoing inflammation. Significance: Our study was the first to show the biochemical characteristics of the [H-3]D-deprenyl binding site in inflamed human synovium. We confirmed that d-deprenyl could differentiate between patients with varying severity of synovitis in the knee joint by binding to a protein target distinct from monoamine oxidase B. more...