Comparison of the analgesic effects of "superficial" and "deep" repetitive transcranial magnetic stimulation in patients with central neuropathic pain: a randomized sham-controlled multicenter international crossover study.

ABSTRACT: We directly compared the analgesic effects of "superficial" and 'deep" repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex in patients with central neuropathic pain. Fifty-nine consecutive patients were randomly assigned to active or sham "superficial" (using a figure-of-8 [F8]-coil) or "deep" (using a Hesed [H]-coil) stimulation according to a double-blind crossover design. Each treatment period consisted of 5 daily stimulation sessions and 2 follow-up visits at 1 and 3 weeks after the last stimulation session. The primary outcome was the comparison of the mean change in average pain intensity over the course of the treatment (group × time interaction). Secondary outcomes included neuropathic symptoms (NPSI), pain interference, patient global impression of change (PGIC), anxiety, depression, and catastrophizing. In total, 51 patients participated in at least one session of both treatments. There was a significant interaction between "treatment" and "time" (F = 2.7; P = 0.0024), indicating that both figure-8 (F8-coil) and H-coil active stimulation induced significantly higher analgesic effects than sham stimulation. The analgesic effects of both types of coils had a similar magnitude but were only moderately correlated ( r = 0.39, P = 0.02). The effects of F8-coil stimulation appeared earlier, whereas the effects of H-coil stimulation were delayed, but tended to last longer (up to 3 weeks) as regards to several secondary outcomes (PGIC and total NPSI score). In conclusion, "deep" and "superficial" rTMS induced analgesic effects of similar magnitude in patients with central pain, which may involve different mechanisms of action.

Thermal grill illusion of pain in patients with chronic pain: a clinical marker of central sensitization?

ABSTRACT: The thermal grill illusion of pain (TGIP) is a paradoxical burning pain sensation elicited by the simultaneous application of innocuous cutaneous warm and cold stimuli with a thermode ("thermal grill") consisting of interlaced heated and cooled bars. Its neurophysiological mechanisms are unclear, but TGIP may have some mechanisms in common with pathological pain, including central sensitization in particular, through the involvement of N-methyl- d -aspartate receptors. However, few studies have investigated TGIP in patients with chronic pain and its clinical relevance is uncertain. We hypothesized that the TGIP would be increased in comparison with controls in patients with fibromyalgia or irritable bowel syndrome, which are regarded as typical "nociplastic" primary pain syndromes related to changes in central pain processing. We compared the sensations elicited by a large range of combinations of temperature differentials between the warm and cold bars of a thermal grill applied to the hand between patients with fibromyalgia (n = 30) or irritable bowel syndrome (n= 30) and controls (n = 30). The percentage of TGIP responses and the intensity and unpleasantness of TGIP were significantly greater in patients than controls. Furthermore, positive correlations were found between TGIP intensity and clinical pain intensity and between TGIP intensity and the cold pain threshold measured on the hand. These results are consistent with our working hypothesis of shared mechanisms between TGIP and clinical pain mechanisms in patients with nociplastic chronic pain syndromes and suggest that TGIP might represent a clinical marker of central sensitization in these patients.

Homocysteine, cardiovascular disease risk factors, and habitual diet in the French Supplementation with Antioxidant Vitamins and Minerals Study.

BACKGROUND: An elevated plasma total homocysteine (tHcy) concentration seems to increase the risk of cardiovascular disease. OBJECTIVE: We evaluated the determinants of tHcy in healthy French adults. DESIGN: tHcy was measured by HPLC and fluorometric detection in 1139 women and 931 men aged 35-60 y. Subjects were participants of the Supplementation with Antioxidant Vitamins and Minerals Study, which investigates the effects of antioxidant supplementation on chronic diseases. Red blood cell folate (RBCF), plasma vitamins B-6 and B-12, and cardiovascular disease risk factors were also measured. The habitual diet was assessed in 616 subjects. Cross-sectional analyses were adjusted for age, smoking, energy intake, and concentration or intake of folate and vitamin B-6, where appropriate. RESULTS: The mean (+/-SD) tHcy concentration was 8.74 +/- 2.71 micro mol/L in women and 10.82 +/- 3.49 micro mol/L in men. In women, tHcy was positively related to age (P = 0.001), apolipoprotein B (P < 0.01), serum triacylglycerol (P < 0.01), fasting glucose (P = 0.02), and coffee and alcohol consumption (both P < 0.01) and inversely related to RBCF (P = 0.11) and plasma vitamin B-12 (P = 0.08) and vitamin B-6 (P = 0.01) intakes. In men, tHcy was positively associated with body mass index (P = 0.03), blood pressure (P < 0.02), serum triacylglycerol (P < 0.01), fasting glucose (P = 0.01), and energy intake (P < 0.01) and inversely associated with physical activity (P = 0.04), RCBF (P = 0.02), plasma vitamin B-12 (P = 0.09), and dietary fiber (P < 0.01), folate (P = 0.03), and vitamin B-6 (P = 0.09) intakes. CONCLUSION: To control tHcy, decreasing coffee and alcohol consumption may be important in women, whereas increasing physical activity, dietary fiber, and folate intake may be important in men.

Effects of a 3-mo consumption of short-chain fructo-oligosaccharides on parameters of colorectal carcinogenesis in patients with or without small or large colorectal adenomas.

Intervention studies of colorectal adenoma recurrence have demonstrated the need for surrogate markers of the cancer risk. Short-chain fructo-oligosaccharides (sc-FOS) have protective actions on colon carcinogenesis in animal models. We investigated differences in biological markers between adenoma and adenoma-free subjects, before and after 3 mo of daily intake of 10 g sc-FOS, within a multicenter study. After a full colonoscopy, 3 groups were studied at baseline and after 3 mo: 26 subjects with small colorectal adenoma(s), 18 with large adenoma(s), and 30 with no adenoma. At baseline, the mean fecal butyrate concentration was significantly lower in the adenoma groups than in the adenoma-free group (12.01 +/- 5.08 vs. 17.28 +/- 7.34 mmol/g dry weight) but was significantly increased in that group after 3-mo ingestion of sc-FOS (15.7 +/- 8.0 mmol/g; P = 0.02). In subjects without adenoma, sc-FOS ingestion was associated with a decrease in fecal lithocholic acid (P = 0.02) and an increase in cholic acid (P = 0.02), chenodeoxycholic acid (P = 0.04), total primary bile acids (P = 0.03), and ursodeoxycholic acid (P = 0.05). Fecal pH, blood parameters, and crypt cell proliferation were not significantly modified by sc-FOS ingestion in either group. In subjects with and without adenoma, sc-FOS affects some aspects of the colonic environment, which may be involved in prevention of colorectal neoplasia.

Fecal primary bile acids and serum cholesterol are associated with colorectal adenomas.

In order to identify biomarkers of colorectal tumors, 20 subjects with colorectal adenomas were compared with 20 controls as regards fecal parameters (pH, short-chain fatty acids, bile acids, and sterols), blood parameters (bile acids, cholesterol, triglycerides, glycemia and insulinemia), and rectal cell proliferation. Variables were compared by unconditional logistic regression, controlling for gender. There were significant and positive associations between risk of adenoma and total fecal primary bile acids and serum cholesterol, with odds ratios for the third versus first tertile = 9.4 (P for trend = 0.03) and 8.6 (P for trend = 0.04), respectively. There was a trend towards an increased triglycerides level in adenoma subjects compared with controls (P = 0.08). These three parameters correlated with cell proliferation, although cell proliferation itself was not significantly associated with adenomas. In conclusion, these results suggest that fecal primary bile acids and serum cholesterol are markers of early events of colorectal carcinogenesis.