Increased capsaicin receptor TRPV1 in skin nerve fibres and related vanilloid receptors TRPV3 and TRPV4 in keratinocytes in human breast pain

BACKGROUND: Breast pain and tenderness affects 70% of women at some time. These symptoms have been attributed to stretching of the nerves with increase in breast size, but tissue mechanisms are poorly understood. METHODS: Eighteen patients (n = 12 breast reduction and n = 6 breast reconstruction) were recruited and assessed for breast pain by clinical questionnaire. Breast skin biopsies from each patient were examined using immunohistological methods with specific antibodies to the capsaicin receptor TRPV1, related vanilloid thermoreceptors TRPV3 and TRPV4, and nerve growth factor (NGF). RESULTS: TRPV1-positive intra-epidermal nerve fibres were significantly increased in patients with breast pain and tenderness (TRPV1 fibres / mm epidermis, median [range] – no pain group, n = 8, 0.69 [0–1.27]; pain group, n = 10, 2.15 [0.77–4.38]; p = 0.0009). Nerve Growth Factor, which up-regulates TRPV1 and induces nerve sprouting, was present basal keratinocytes: some breast pain specimens also showed NGF staining in supra-basal keratinocytes. TRPV4-immunoreactive fibres were present in sub-epidermis but not significantly changed in painful breast tissue. Both TRPV3 and TRPV4 were significantly increased in keratinocytes in breast pain tissues; TRPV3, median [range] – no pain group, n = 6, 0.75 [0–2]; pain group, n = 11, 2 [1-3], p = 0.008; TRPV4, median [range] – no pain group, n = 6, [0–1]; pain group, n = 11, 1 [0.5–2], p = 0.014). CONCLUSION: Increased TRPV1 intra-epidermal nerve fibres could represent collateral sprouts, or re-innervation following nerve stretch and damage by polymodal nociceptors. Selective TRPV1-blockers may provide new therapy in breast pain. The role of TRPV3 and TRPV4 changes in keratinocytes deserve further study

The effect of addition of modified guar gum to a low-energy semisolid meal on appetite and body weight loss

Int J Obes Relat Metab Disord 2001 Mar;25(3):307-15 Related Articles, Books, LinkOut The effect of addition of modified guar gum to a low-energy semisolid meal on appetite and body weight loss. Kovacs EM, Westerterp-Plantenga MS, Saris WH, Goossens I, Geurten P, Brouns F. Department of Human Biology, Maastricht University, Maastricht, The Netherlands. [email protected] OBJECTIVE: To investigate the effect of addition of modified guar gum (GG) to a low-energy semisolid meal on appetite and body weight (BW) loss. SUBJECTS: Twenty eight mainly overweight male volunteers (age, 19-56 y; body mass index, 29+/-2 kg x m(-2); BW, 89.4+/-9.2 kg). DESIGN: Baseline of one week with self-selected diet. Three treatments of 2 weeks with a low-energy diet divided over three times a day, consisting of a semisolid meal with (SSM+) or without GG (SSM) or a solid meal (SM) with the same energy content (947 kJ) and macronutrient composition, and a dinner of the subject's own choice. Washout periods lasted 4 weeks. RESULTS: Compared to baseline values, reduction in energy intake and BW loss were similar for SSM+, SSM and SM. Appetite (hunger, desire to eat or estimation of how much one could eat) was increased in SSM and in SM compared to baseline, but not in SSM+. Satiety and fullness in SSM+, SSM and SM were similar to baseline. Any intervention was more effective on BW loss when it took place the first time compared to the second and third times (2.6+/-0.2 kg, 1.7+/-0.2 kg and 1.1+/-0.2 kg, respectively; P<0.001). The SM-SSM+-SSM sequence was more effective on BW loss compared to the SSM+-SSM-SM sequence (5.6+/-1.0 and 2.5+/-0.6 kg, respectively; P<0.05). CONCLUSION: All the three treatments were equally effective with respect to BW loss. GG addition to a semisolid meal prevented an increase in appetite, hunger and desire to eat, which increase was present in the other treatments. However, differences between treatments were not statistically significant. The order effect shows that repeated 2-week bouts of dieting become increasingly ineffective. The sequence SM-SSM+-SSM was more effective than the sequence SSM+-SSM-SM, probably because compliance was relatively higher with the SSM+ or SSM diet, and compliance decreased towards the end of the complete experiment