Fundamentals of interventional pain medicine

Chronic pain is one of the most common and challenging medical problems facing our society. The specialty of pain medicine has grown steadily in recent years, largely because of the recognition that multiple factors contribute to chronic pain. The practice of pain medicine is multidisciplinary in approach, incorporating modalities from various specialties to ensure the comprehensive evaluation and treatment of the pain patient. The integration of various specialties such as anesthesiology, neurology, neurologic surgery, orthopedic surgery, physical medicine, and psychiatry is essential to treating patients with chronic pain and to establishing continuity of care. Research in the last 30 years has developed a variety of alternatives or adjuncts to opiates for chronic pain, including neuroactive medications, counterstimulation methods, and cognitive-behavioral therapies. Pain medicine specialists have provided leadership in the development of the practice, with the application of a wide verity of central and peripheral nerve blocks, sympathetic and neurolytic blocks, intradiscal procedures, neuromodulation techniques, intrathecal infusion systems, and other technical procedures that are firmly linked to a biomedical model of pain.     

Immune responses to Campylobacter and serum autoantibodies in patients with complex regional pain syndrome

We hypothesised that some complex regional pain syndromes (CRPS) may have a postinfectious and/or autoimmune basis. Sera from 92 patients with CRPS and 92 controls were investigated for immunoreactivity to Campylobacter strains and to rodent tissues. Both IgA-antibodies to Campylobacter and tissue-specific reactivity were often present in patients with short disease duration (< or = 1.5 years). Patients with minimal preceding trauma had stronger nervous tissue-specific reactivity than other patients, regardless of disease duration. These results provide preliminary evidence for immune activation early in CRPS and, additionally, that patients with minimal trauma may comprise an autoimmune subgroup.     

Evidence for C-Reactive Protein's Role in (CRP) Vascular Disease: Atherothrombosis,Immuno-Regulation and CRP

For clinicians plasma C-reactive protein (CRP) levels are the only widely available tests that provide a tangible link between inflammation and atherosclerosis. New AHA/CDC joint guidelines from 2002-03 now include the measurement of CRP as a class IIa recommendation for stratifying patients with known cardiovascular disease (CVD) at a moderate (10-20%) 10-year event risk and a class IIb recommendation for patients without known CVD [1]. While the association of CRP and atherosclerosis is by now accepted, the molecular biology behind the association is evolving rapidly into a fascinating story. While some of the story remains obscure, this review aims to bridge the clinical and basic science and identify what is known about the role of this ancient molecule in atherosclerosis. The review covers CRP's interaction with atherosclerosis' major ingredients and cell types including the endothelium, monocytes and neutrophils, lipoproteins and the complement system. Taken together, the clinical and basic science leave the tantalizing impression that CRP has a fundamental role in atherogenesis, and hint at a more complex immunomodulatory effect which transforms the acute inflammatory response to vascular injury into the chronic inflammation seen in atherosclerosis.     

Human leukocyte antigen-DQB1 alleles are not associated with schizophrenia in Kuwaiti Arabs

Schizophrenia is among the most severe and debilitating of psychiatric disorders and has a complex mode of inheritance. A susceptibility locus has been identified on chromosome 6 and some association studies involving human leukocyte antigen (HLA) genes have reported diverse results. The objective of the present study was to determine if there is an association between HLA-DQB1 alleles and schizophrenia in Kuwaiti Arabs. The frequency of HLA-DQB1 alleles was determined in a cohort of 195 Kuwaiti Arabs consisting of 81 schizophrenia patients and 114 ethnically matched healthy controls, using a polymerase chain reaction-sequence specific primers method. A total of nine DQB1 alleles were identified in this Kuwaiti cohort. The most prevalent DQB1 alleles in Kuwaiti schizophrenia patients were *0601 (28%), *0201 (23%) and *0501 (16%), respectively. However, no significant difference in the allele frequency was detected between schizophrenia patients and the controls. The DQB1*0602 allele, which has been negatively associated in African-Americans in previous reports, was not detected in the present Kuwaiti schizophrenia patients or controls.     

Minocycline inhibits smooth muscle cell proliferation, migration and neointima formation after arterial injury

The tetracyclines are antimicrobials that also inhibit expression of certain matrix metalloproteinases (MMPs). We conducted a series of experiments to determine if minocycline could inhibit MMP expression and limit human aortic smooth muscle cell (SMC) proliferation and migration. Analysis of SMC proliferation was performed after cells were grown in minocycline-incubated media. SMC migration activity was assayed in a micro-Boyden chamber. Western blotting revealed that minocycline reduced SMC production of MMP-2 in a dose dependent manner. Increasing doses of minocycline progressively reduced SMC proliferation to 49% of control values and limited SMC migration to 15% of control. When administered to rats with balloon injured carotid arteries, intraperitoneal doses of minocycline (70-100 mg/kg) reduced neointima formation by 76%, but were associated with liver toxicity. Higher doses were lethal and lower doses were ineffective. Minocycline, applied to injured arteries in a pluronic gel with a low pH, was also ineffective. In summary, minocycline lowers MMP-2 expression, reduces SMC proliferation and migration, and inhibits neointimal hyperplasia, but its efficacy is limited by systemic toxicity.     

Prostate secretory protein PSP-94 decreases tumor growth and hypercalcemia of malignancy in a syngenic in vivo model of prostate cancer

Prostate cancer is a common malignancy affecting men, which is often associated with skeletal metastases resulting in significant morbidity and mortality. In this hormone-dependent cancer, low levels of a prostate secretory protein of 94 amino acids (PSP-94) are associated with advanced disease stage. In the current study, we have examined the effect of PSP-94 on prostate cancer growth and experimental metastases to the skeleton. For these studies, MatLyLu rat prostate cancer cells were transfected with full-length cDNA encoding parathyroid hormone-related protein [PTHrP (MatLyLu-PTHrP cells)], which is known to be the major pathogenetic factor for malignancy-associated hypercalcemia. MatLyLu-PTHrP cells were inoculated s.c. into the right flank or via intracardiac route into the left ventricle of syngeneic male Copenhagen rats. Intracardiac inoculation of MatLyLu cells routinely results in the development of tumors in the lumbar vertebrae, resulting in hind-limb paralysis. Animals were infused with different doses of PSP-94 (0.1, 1.0, and 10.0 micro g/kg/day) starting on the day of tumor cell inoculation. Time of hind-limb paralysis and tumor volume were determined, and comparison was made between PSP-94-treated animals and control animals receiving vehicle alone. At the end of the study, animals were sacrificed, and plasma calcium, plasma PTHrP, and tumor PTHrP levels were determined. Whereas the highest dose of PSP-94 caused a modest but statistically significant delay in the development of hind-limb paralysis, a marked dose-dependent decrease in primary tumor volume was seen in experimental animals receiving PSP-94 due to its ability to promote tumor cell apoptosis. Furthermore, whereas control animals routinely developed hypercalcemia due to PTHrP production, treatment with PSP-94 led to a near normalization of plasma calcium and a marked reduction in PTHrP production as determined by radioimmunoassay and immunohistochemistry. Collectively, these results demonstrate the ability of PSP-94 to be an effective treatment modality for prostate cancer, where decrease in plasma PTHrP and calcium levels can serve as useful biochemical markers for monitoring the efficacy of this novel antitumor agent.