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Human neuroimaging studies and complementary animal experiments now identify the gross elements of the brain involved in the chronification of pain. We briefly review these advances in relation to somatic and orofacial persistent pain conditions. First, we emphasize the importance of reverse translational research for understanding chronic pain-that is, the power of deriving hypotheses directly from human brain imaging of clinical conditions that can be invasively and mechanistically studied in animal models. We then review recent findings demonstrating the importance of the emotional brain (i.e., the corticolimbic system) in the modulation of acute pain and in the prediction and amplification of chronic pain, contrasting this evidence with recent findings regarding the role of central sensitization in pain chronification, especially for orofacial pain. We next elaborate on the corticolimbic circuitry and underlying mechanisms that determine the transition to chronic pain. Given this knowledge, we advance a new mechanistic definition of chronic pain and discuss the clinical implications of this new definition as well as novel therapeutic potentials suggested by these advances. [ABSTRACT FROM AUTHOR]

Study Design:Comparison of diagnostic tests; methodological validation.Objectives:Primary: to investigate the precision and reliability of a knee bone mineral density (BMD) assessment protocol that uses an existing dual energy X-ray absorptiometry (DXA) forearm acquisition algorithm in individuals with spinal cord injury (SCI). Secondary: to correlate DXA-based knee areal BMD with volumetric BMD assessments derived from quantitative computed tomography (QCT).Setting:Academic medical center, Chicago, IL, USA.Methods:Participants: a convenience sample of 12 individuals with acute SCI recruited for an observational study of bone loss and 34 individuals with chronic SCI who were screened for a longitudinal study evaluating interventions to increase BMD. Main outcome measures: root-mean-square standard deviation (RMS-SD) and intra/inter-rater reliability of areal BMD acquired at three knee regions using an existing DXA forearm acquisition algorithm; correlation of DXA-based areal BMD with QCT-derived volumetric BMD.Results:The RMS-SD of areal BMD at the distal femoral epiphysis, distal femoral metaphysis and proximal tibial epiphysis averaged 0.021, 0.012 and 0.016 g cm−2, respectively, in acute SCI and 0.018, 0.02 and 0.016 g cm−2 in chronic SCI. All estimates of intra/inter-rater reliability exceeded 97% and DXA-based areal BMD was significantly correlated with QCT-derived volumetric BMD at all knee regions analyzed.Conclusions:Existing DXA forearm acquisition algorithms are sufficiently precise and reliable for short-term assessments of knee BMD in individuals with SCI. Future work is necessary to quantify the reliability of this approach in longitudinal investigations and to determine its ability to predict fractures and recovery potential.Sponsorship:This work was funded by the Department of Defense, grant number DOD W81XWH-10-1-0951, with partial support from Merck & Co, Inc. [ABSTRACT FROM AUTHOR]

Background: Combinations of analgesic drugs provide the opportunity for better efficacy with less overall morbidity than provided by single analgesic agents. This article discusses the rationale, efficacy and safety for a novel analgesic combination: tramadol and acetaminophen (paracetamol). Methods: Data supporting the rationale of combining tramadol and acetaminophen to provide pain relief will be reviewed in addition to clinical data demonstrating the efficacy and safety of this combination in acute and chronic pain states. Results: Tramadol and acetaminophen are a rational combination product in that their mechanisms of action do not overlap and that in preclinical studies this combination acts synergistically. Also, this combination would be expected to provide more rapid pain relief than tramadol alone, and more persistent pain relief than acetaminophen alone. Moreover, each compound is broken down along separate metabolic pathways. Acute dental pain studies showed that pain relief and improvements in pain intensity associated with tramadol 75 mg plus acetaminophen 650 mg are superior to placebo, or tramadol or acetaminophen alone. This combination provided a rapid onset of action, identical to that achieved with acetaminophen alone, but the pain relief was also sustained, as for tramadol alone. Tramadol/acetaminophen also had the same adverse event profile as tramadol monotherapy. A chronic low back/osteoarthritic pain study showed that the drug combination can also be used similarly to codeine/acetaminophen combinations in treating benign chronic pain. The safety profile of the tramadol/ acetaminophen combination is at least as favourable as that of codeine/acetaminophen, and is well tolerated with long-term use. Conclusions: Tramadol/acetaminophen combination is a new preparation that is effective in acute or chronic moderate-to-moderately severe pain. It benefits from the complementary actions of the constituent analgesics, having the rapid onset of... [ABSTRACT FROM AUTHOR]

Chronic pain affects 75 million US citizens. A number of pharmacologic treatments are available for chronic pain that does not respond adequately to nonpharmacologic methods. Long the mainstay of chronic pain management, nonsteroidal anti-inflammatory drugs (NSAIDs) are known to be associated with gastrointestinal (GI) and renal toxicities, a particular problem for the elderly population, which commonly experiences chronic pain, such as that associated with osteoarthritis (OA). Several non-NSAID, non-narcotic therapies are available for noninflammatory pain. Acetaminophen is as effective as NSAIDs for the management of mild-to-moderate OA pain and is the recommended first-line therapy by the American College of Rheumatology (ACR). Propoxyphene, widely believed to be safe and effective, may, in fact, be no more effective-and perhaps less effective-than acetaminophen or ibuprofen. A relatively new analgesic, tramadol, appears to be a useful therapy for patients who do not receive adequate pain relief with acetaminophen and are at risk for NSAID-related side effects. For localized chronic pain associated with OA, topical capsaicin is also an effective analgesic. [ABSTRACT FROM AUTHOR]

Forty-one patients with active and refractory rheumatoid arthritis (RA) received a total of 100, 250 or 400 mg of CAMPATH-1H (CAMPATH is a trademark of Glaxo-Wellcome group companies, registered in the US Patent and Trademark Office) over 5 or 10 days in an open, uncontrolled study. Following therapy, patients were monitored for adverse effects and disease activity for 6 months. Therapy was associated with prolonged peripheral blood lymphopenia in all dosing cohorts. During the month immediately following therapy, lymphopenia was most profound in the 400 mg cohorts. The first dose of monoclonal antibody (Mab) was associated with a ‘flu’-like syndrome, more pronounced at higher initial doses. One patient developed haemolytic-uraemic syndrome. There were a number of dose-related infections during the early post-treatment period and one fatal opportunistic infection which followed additional immunosuppressive therapy. Antiglobulin responses developed in 9 of 31 patients tested. The majority of patients showed symptomatic improvement following therapy and 20% of patients maintained a 50% Paulus response at 6 months, all of whom were in the 250 or 400 mg cohorts. CAMPATH- 1H appears to be an effective treatment for RA. Allowing for the small number of patients treated, infections were more common with higher doses, although this was not true for adverse events overall, and therapeutic responses were more sustained at higher dosing levels. The broad specificity of CAMPATH- 1H may be appropriate for the immunotherapy of RA and future studies should aim to define a dose with an optimal therapeutic ratio. [ABSTRACT FROM PUBLISHER]

Among their immunological alterations patients with systemic lupus erythematosus (SLE) have been shown to have diminished natural killer (NK) cell activity. This abnormality is at least in part related to humoral factors, as sera from patients with SLE can inhibit the NK activity of peripheral blood mononuclear cells from normal individuals. The present study extends these findings to demonstrate that the inhibitory ability of sera from patients with SLE varies with disease activity. Furthermore, sera from patients with active SLE containing interferon (IFN), a potent stimulator of NK activity, were equally or more inhibitory than sera which did not contain IFN. Thus the factors in SLE sera which can inhibit NK function vary with disease activity and cannot be overcome by IFN present in these sera. [ABSTRACT FROM AUTHOR]

Fifty-three patients under the age of 5 years with definite juvenile chronic polyarthritis (JCP) were examined for serological evidence of rubella infection. The prevalence of rubella antibody was found to be low and did not differ significantly from that found in normal children of similar age. Patients with JCP and antibody to rubella virus had a clinical course indistinguishable from those with no detectable rubella antibody. [ABSTRACT FROM PUBLISHER]

Purpose: To administer recombinant erythropoietin to patients with rheumatoid arthritis who had significant anemia, while monitoring hematologic and rheumatologic clinical responses as well as potential toxicity.Patients and Methods: Seventeen patients with rheumatoid arthritis from five rheumatology care settings were studied. The patients had initial hematocrits of 34% or less and stable clinical status, and were not being treated with second-line drugs or corticosteroids. An 8-week randomized double-blind study involving various dosages of recombinant erythropoietin, as well as placebo, was followed by a 24-week open-label study in which dosage could be titrated to achieve a normal hematocrit.Results: In the 8-week randomized study, four of 13 patients who received injections of recombinant erythropoietin showed a hematologic response, arbitrarily defined as at least a 6-unit increase in hematocrit. None of four placebo-treated patients showed a meaningful hematologic response. All 11 patients who completed the subsequent 24-week open-label study reached a normal hematocrit level at some time during the study, and 10 of 11 showed an increase of hematocrit 6 units or greater. At least one adjustment, i.e., an increase, decrease, or omission of the erythropoietin dosage, was required in all patients to maintain the hematocrit at a target range of 35% for women or 40% for men. Meaningful changes were not seen in patients' capacity to perform activities of daily living or pain levels during either the 8-week randomized study or the 24-week open-label study. No adverse effects were associated with recombinant erythropoietin therapy.Conclusion: Patients with rheumatoid arthritis showed excellent hematologic responses to recombinant erythropoietin, without toxicity, during careful monitoring for appropriate dosage adjustment, although a meaningful change in rheumatologic clinical status was not seen. [ABSTRACT FROM AUTHOR]