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77 Thus, obesity involves various endocrine changes. There is evidence that such endocrine changes may have a role in altered pain modulation in obesity. Research suggests that obesity may be characterized by a low-grade chronic inflammatory state as reflected by elevated levels in many inflammatory markers in the serum, such as interleukin-6 (IL-6) and C-reactive protein (CRP).78 Macrophage accumulation in adipose tissues has also been demonstrated in obese humans,79 which is known to play an important role in production and release of inflammatory mediators.80 Thus, obesity can be considered to reflect systemic inflammation which may contribute to pain. Enhanced reactivity of proinflammatory [http://en.wikipedia.org/wiki/Mycoplasma MycoClean Mycoplasma Removal Kit] cytokines has been noted in obese people following a surgery.81 In fibromyalgia women, CRP level was significantly correlated with BMI.23 A recent population-based study82 also suggests that a high level of CRP adds a risk of having low back pain in obese people; obese people with elevated CRP level (>3.0 mg/dL) had an OR of 2.87 (95% CI, 1.18�C6.96) of having low back pain compared to those whose CRP level was less than 3.0 mg/dL, suggesting the potential mediating role of systemic inflammation in the relationship between obesity and pain. Leptin is a hormone that signals energy intake and stores to the brain, and obesity is associated with high leptin levels.83 In end-stage OA, joint pain was significantly associated with synovial leptin level.84 Increased leptin level in OA joints was found in obese [http://www.selleckchem.com/products/MG132.html selleck chemicals] people, and when present, it seems to facilitate further inflammation and joint damage in general.85 Other obesity-related hormones and peptides, such as ghrelin and galanin, may also be involved in obesity-related change in pain perception.86,87 Recently, a role of vitamin D in obesity and chronic pain has been gaining attention. Inadequate [http://www.selleckchem.com/products/Rapamycin.html Rapamycin mw] level of vitamin D appears to be more common in obese people.88 Poor skeletal mineralization due to vitamin D deficiency may lead to complaints of achiness in the joints and muscles. Low level of vitamin D is common in people with nonspecific musculoskeletal pain,89 particularly in women.90,91 A recent report also found that among people with knee OA, greater proportion of obese patients had vitamin D deficiency (defined as