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Inclusion of cocoa as a dietary supplement represses expression of inflammatory proteins in spinal trigeminal nucleus in response to chronic trigeminal nerve stimulation.

ABSTRACT: Central sensitization is implicated in the pathology of temporomandibular joint disorder and other types of orofacial pain. We investigated the effects of dietary cocoa on expression of proteins involved in the development of central sensitization in the spinal trigeminal nucleus (STN) in response to inflammatory stimulation of trigeminal nerves.Male Sprague-Dawley rats were fed either a control diet or an isocaloric diet consisting of 10% cocoa powder 14 days prior to bilateral injection of complete Freund's adjuvant (CFA) into the temporomandibular joint to promote prolonged activation of trigeminal ganglion neurons and glia. While dietary cocoa stimulated basal expression of glutamate-aspartate transporter and mitogen-activated protein kinase phosphatase-1 when compared to animals on a normal diet, cocoa suppressed basal calcitonin gene-related peptide levels in the STN. CFA-stimulated levels of protein kinase A, P2X3 , P-p38, glial fibrillary-associated protein, and OX-42, whose elevated levels in the STN are implicated in central sensitization, were repressed to near control levels in animals on a cocoa-enriched diet. Similarly, dietary cocoa repressed CFA-stimulated inflammatory cytokine expression.Based on our findings, we speculate that cocoa-enriched diets could be beneficial as a natural therapeutic option for temporomandibular joint disorder and other chronic orofacial pain conditions.

SUBMITTER: Cady RJ

PROVIDER: S-EPMC3777559 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Inclusion of cocoa as a dietary supplement represses expression of inflammatory proteins in spinal trigeminal nucleus in response to chronic trigeminal nerve stimulation.

Cady Ryan J RJ Denson Jennifer E JE Durham Paul L PL

Molecular nutrition & food research 20130411 6

<h4>Scope</h4>Central sensitization is implicated in the pathology of temporomandibular joint disorder and other types of orofacial pain. We investigated the effects of dietary cocoa on expression of proteins involved in the development of central sensitization in the spinal trigeminal nucleus (STN) in response to inflammatory stimulation of trigeminal nerves.<h4>Methods and results</h4>Male Sprague-Dawley rats were fed either a control diet or an isocaloric diet consisting of 10% cocoa powder 1 ...[more]

PMID: 23576361

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Project description:ObjectiveTo explore the safety and efficacy of external trigeminal nerve stimulation (eTNS) in patients with drug-resistant epilepsy (DRE) using a double-blind randomized controlled trial design, and to test the suitability of treatment and control parameters in preparation for a phase III multicenter clinical trial.MethodsThis is a double-blind randomized active-control trial in DRE. Fifty subjects with 2 or more partial onset seizures per month (complex partial or tonic-clonic) entered a 6-week baseline period, and then were evaluated at 6, 12, and 18 weeks during the acute treatment period. Subjects were randomized to treatment (eTNS 120 Hz) or control (eTNS 2 Hz) parameters.ResultsAt entry, subjects were highly drug-resistant, averaging 8.7 seizures per month (treatment group) and 4.8 seizures per month (active controls). On average, subjects failed 3.35 antiepileptic drugs prior to enrollment, with an average duration of epilepsy of 21.5 years (treatment group) and 23.7 years (active control group), respectively. eTNS was well-tolerated. Side effects included anxiety (4%), headache (4%), and skin irritation (14%). The responder rate, defined as >50% reduction in seizure frequency, was 30.2% for the treatment group vs 21.1% for the active control group for the 18-week treatment period (not significant, p = 0.31, generalized estimating equation [GEE] model). The treatment group experienced a significant within-group improvement in responder rate over the 18-week treatment period (from 17.8% at 6 weeks to 40.5% at 18 weeks, p = 0.01, GEE). Subjects in the treatment group were more likely to respond than patients randomized to control (odds ratio 1.73, confidence interval 0.59-0.51). eTNS was associated with reductions in seizure frequency as measured by the response ratio (p = 0.04, analysis of variance [ANOVA]), and improvements in mood on the Beck Depression Inventory (p = 0.02, ANOVA).ConclusionsThis study provides preliminary evidence that eTNS is safe and may be effective in subjects with DRE. Side effects were primarily limited to anxiety, headache, and skin irritation. These results will serve as a basis to inform and power a larger multicenter phase III clinical trial.Classification of evidenceThis phase II study provides Class II evidence that trigeminal nerve stimulation may be safe and effective in reducing seizures in people with DRE.

Project description:Clinical imaging studies have revealed that the hypothalamus is activated in migraine patients prior to the onset of and during headache and have also shown that the hypothalamus has increased functional connectivity with the spinal trigeminal nucleus. The dopaminergic system of the hypothalamus plays an important role, and the dopamine-rich A11 nucleus may play an important role in migraine pathogenesis. We used intraperitoneal injections of glyceryl trinitrate to establish a model of acute migraine attack and chronicity in mice, which was verified by photophobia experiments and von Frey experiments. We explored the A11 nucleus and its downstream pathway using immunohistochemical staining and neuronal tracing techniques. During acute migraine attack and chronification, c-fos expression in GABAergic neurons in the A11 nucleus was significantly increased, and inhibition of DA neurons was achieved by binding to GABA A-type receptors on the surface of dopaminergic neurons in the A11 nucleus. However, the expression of tyrosine hydroxylase and glutamic acid decarboxylase proteins in the A11 nucleus of the hypothalamus did not change significantly. Specific destruction of dopaminergic neurons in the A11 nucleus of mice resulted in severe nociceptive sensitization and photophobic behavior. The expression levels of the D1 dopamine receptor and D2 dopamine receptor in the caudal part of the spinal trigeminal nucleus candalis of the chronic migraine model were increased. Skin nociceptive sensitization of mice was slowed by activation of the D2 dopamine receptor in SP5C, and activation of the D1 dopamine receptor reversed this behavioral change. GABAergic neurons in the A11 nucleus were activated and exerted postsynaptic inhibitory effects, which led to a decrease in the amount of DA secreted by the A11 nucleus in the spinal trigeminal nucleus candalis. The reduced DA bound preferentially to the D2 dopamine receptor, thus exerting a defensive effect against headache.

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Inclusion of cocoa as a dietary supplement represses expression of inflammatory proteins in spinal trigeminal nucleus in response to chronic trigeminal nerve stimulation.

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Inclusion of cocoa as a dietary supplement represses expression of inflammatory proteins in spinal trigeminal nucleus in response to chronic trigeminal nerve stimulation.

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