Objective. The term chronic widespread pain refers to a group of painful diseases of poorly understood pathophysiology. One major subgroup is fibromyalgia (FM), as defined by the criteria of the American College of Rheumatology. Among other hypotheses, a potential pathophysiologic role of cytokines in chronic widespread pain has been proposed. We undertook this study to investigate whether cytokine profiles differ in patients with chronic widespread pain and controls.Methods. We analyzed cytokine expression patterns in 40 patients with chronic widespread pain (26 of whom had FM), 40 age-and sex-matched healthy controls, and an additional 15 patients with chronic widespread pain who were recruited from a different center. Expression of messenger RNA (mRNA) for interleukin-2 (IL-2), IL-4, IL-8, IL-10, tumor necrosis factor ␣ (TNF␣), and transforming growth factor ␤1 (TGF␤1) in peripheral blood was analyzed using quantitative real-time polymerase chain reaction (PCR). Serum protein levels were measured by enzyme-linked immunosorbent assay.Results. We found significantly lower relative gene expression (P < 0.0001 for IL-4; P ‫؍‬ 0.03 for IL-10) and lower levels of serum protein concentrations (P < 0.0001 for IL-4; P ‫؍‬ 0.04 for IL-10) of the Th2 cytokines IL-4 and IL-10 in patients with chronic widespread pain than in the control group. This finding was corroborated in an additional group of 15 patients with chronic widespread pain. There were no significant differences between the groups in levels of mRNA for IL-2, IL-8, TNF␣, or TGF␤1. Protein data paralleled the real-time PCR results.Conclusion. Chronic widespread pain is associated with a lack of antiinflammatory and analgesic Th2 cytokine activity, which may contribute to its pathogenesis.

Bo vine colostrum as a bi o logic in clin i cal med i cine: A re view-Part II Ab stract. The value of bo vine colostrum as a bi o logic in med i cine is doc u mented in clin i cal tri als and sup ported by rel a tively large databases con tain ing case re ports and an ec dotal find ings. The main ac tions in clude an an ti bac te rial ef fect and mod u la tion of the im mune re sponse. The abil ity of bo vine colos trum con cen trates (BCC are polyvalent bo vine colostrum con cen trates pro duced from the colos trums of sev eral 100 cows) to neu tral ize lipopolysaccharides, i.e. endo tox ins aris ing from Gram-neg a tive bac te rial pathogens and to in hibit enterogenic endotoxemia in an i mal mod els as shown in the last re view to have its coun ter part in pa tient ther apy. Clin ical tri als with BCC pro vide ev i dence that oral ap pli ca tion re duces the in flux of LPS from the gut and this ap pears to be a ma jor mech anism un der ly ing its ther a peu tic ef fect in patients at risk for Gram-neg a tive sep tic shock; data from two well-con trolled clin i cal stud ies with a to tal of 100 sur gi cal pa tients have shown that the in hi bi tion of in tes ti nal LPS absorp tion mea sured af ter the ap pli ca tion of BCC not only re duced the LPS lev els in the pe riph eral blood but also in flam ma tory param e ters like IL-6 and CRP were found to be di min ished. The usual daily dose of the com mer cially avail able BCC prep a ra tion, Lactobin ® (LC1) is 10-20 g daily, but higher doses can be used in the ma jor ity of pa tients be cause of the low in ci dence of in tol er ance prob lems. In chronic di ar rhea in volv ing severe forms of sec ond ary immunodeficiencies, pa tients re ceiv ing LC1 were disease-free for about 4 weeks but the re sponse may be lower in pa tients with AIDS. BCC is ef fec tive in in fants with hem or rhagic di ar rhea caused by in fec tions with enterohemorrhagic E. coli and re duces the like li hood of the disease pro gress ing to a hemolytic uremic syndrome. The safety of newer BCC prod ucts ob tained from BSE-free re gions seems now be yond con ten tion. In the case of LC1, which was used as a com mer cial di etary food stuff in Ger many un til 1992 and tested in three Phase 1 and 5 clin i cal stud ies (two tri als in pa tients with sec ond ary immunodeficiencies, one in sur gi cal pa tients with gas tro in tes ti nal dis orders, one in pa tients un der go ing open heart sur gery and one in pe di at ric pa tients with EHEC in fec tions), there were no cases of BSE-as so ci ated dis ease such as the new variant of Creutz feldt-Jakob dis ease. Side ef fects of clin i cal rel e vance are lim ited to pos si ble in tol er ance to lac tose and sen si tiv ity to milk pro teins as these are also pres ent in many com monly used food stuffs. Im por tant syn ergis tic ac tions with con ven tional drug ther apies have been ob served with BCC in clud ing a re duc tion in LPS plasma lev els in pa tients with Gram-neg a tive bac te rial in fec tions treated with bac te ri cidal an ti bi ot ics...

The IPs in primary FM and, unexpectedly, CRPS are increased. This study should stimulate further research to determine the implication of altered IP in the disease pathophysiology of FM and CRPS.

Objective. To examine the use of intravenous immunoglobulin (IVIG) in chronic pain.Design. A prospective multiple-dose, open-label cohort study in 130 consecutive patients who suffered from 12 chronic pain syndromes. The largest symptom groups were (number of patients): Fibromyalgia (48); Spinal pain (20); Complex regional pain syndrome (CRPS, 11); Peripheral neuropathic pain (12); and Atypical odontalgia or atypical facial pain (11). All patients had insufficient pain relief with established treatments. Pain relief was recorded using average pain intensity values as documented in standardized diaries. A specific treatment protocol was developed, and patients were enrolled over a 36-month period.Results. Overall, 20% of patients had Ͼ 70% pain relief and 27.7% of patients reported relief between 25% and 70%. Six patients (4.6%) had moderately increased pain levels for a duration of up to 9 weeks. Good relief, of more than 70%, was found in all major symptom groups. Patients with pain of short duration ( Ͻ 2 years) reported high relief rates (33.8% of patients in this group reported relief of Ͼ 70%). No serious adverse events were reported.Conclusions. IVIG may be effective in patients suffering from chronic pain. Controlled studies are needed to evaluate the efficacy of IVIG in these patients. Patients with a good response to IVIG may be models for the study of neuroimmune interactions in chronic pain.

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