leptin and Neurogenic-Inflammation

Obesity and migraine are both highly prevalent disorders in the general population, influenced by genetic and environmental risk factors. In recent studies, obesity was found to be a strong risk factor for transformed migraine and, among migraineurs, obesity was associated with frequent headaches and higher disability scores. Suggested mechanisms included: (i) obesity as a pro-inflammatory state may be associated with neurovascular inflammation in patients with migraine; (ii) elevated levels of plasma calcitonin gene-related peptide (CGRP) in obese individuals may play a role as an important post-synaptic mediator of trigeminovascular inflammation in migraine; (iii) dismodulation in the hypothalamic neuropeptide, orexin, in obese persons may be associated with increased susceptibility to neurogenic inflammation causing migraine attacks; and (iv) leptin and adiponectin can activate proinflammatory cytokine release that is involved in the pathogenesis of migraine. In addition, both conditions are associated with psychiatric co-morbidities, such as depression and anxiety, that can further increase headache frequency and disability. Therefore, the effect of obesity on migraine outcome is important. Weight and BMI should be measured and calculated in all children presenting with migraine, and weight control should be a part of the treatment.

Topics: Adiponectin; Calcitonin Gene-Related Peptide; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Migraine Disorders; Neurogenic Inflammation; Neuropeptides; Orexins; Pediatric Obesity; Risk Factors; Weight Loss

Here, we investigated inflammatory signs of peripheral nerves in leptin-deficient obese ob/ob mice and the modulating effects of the exogenous iron load.. Ob/ob and ob/+ control mice were fed with high, standard, or low iron diet for four months.. We found intraepidermal nerve fiber degeneration in foot skin and low-grade neuropathic abnormalities including mildly slowed motor and compound sensory nerve conduction velocities and low-grade macrophage and T-cell infiltration without overt neuropathology in sciatic nerves of all ob/ob mice. Low dietary iron load caused more pronounced abnormalities than high iron load in ob/ob mice.. Our data suggest that dietary non-heme iron deficiency may be a modulating factor in the pathogenesis of peripheral neuropathy in obese ob/ob mice with metabolic syndrome. Once the mechanisms can be further elucidated, how low dietary iron augments peripheral nerve degeneration and dysfunction via pro-inflammatory pathways and new therapeutic strategies could be developed.. CMAP: compound muscle action potential; cSNCV: compound sensory nerve conduction velocity; IENFD: intraepidermal nerve fiber density; LDL: low-density lipoprotein; MetS: metabolic syndrome; MNCV: motor conduction velocity; NCV: nerve conduction velocity; PN: peripheral neuropathy; PNS: peripheral nervous system; STZ: streptozotocin; T2D: type 2 diabetes mellitus; TNF alpha: tumor necrosis factor alpha; WHO: World Health Organization.

Topics: Animals; Calcium-Binding Proteins; Cytokines; Diabetic Neuropathies; Disease Models, Animal; Iron, Dietary; Leptin; Male; Mice; Mice, Mutant Strains; Microfilament Proteins; Microscopy, Electron, Transmission; Nerve Fibers; Nerve Tissue Proteins; Neural Conduction; Neurogenic Inflammation; Sciatic Nerve; Skin