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

Mol Nutr Food Res. 2013 Jun;57(6):996-1006. doi: 10.1002/mnfr.201200630. Epub 2013 Apr 11.


Scope: 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.

Methods and results: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cacao*
  • Calcitonin Gene-Related Peptide / metabolism
  • Central Nervous System Sensitization / drug effects*
  • Cytokines / metabolism
  • Dietary Supplements*
  • Disease Models, Animal
  • Dual Specificity Phosphatase 1 / metabolism
  • Excitatory Amino Acid Transporter 1 / metabolism
  • Facial Pain / diet therapy
  • Facial Pain / metabolism*
  • Freund's Adjuvant / adverse effects
  • Male
  • Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Temporomandibular Joint Disorders / diet therapy*
  • Temporomandibular Joint Disorders / metabolism
  • Temporomandibular Joint Disorders / physiopathology
  • Tetraspanin 25 / metabolism
  • Trigeminal Nerve / metabolism
  • Trigeminal Nerve / pathology
  • Trigeminal Nucleus, Spinal / drug effects*
  • Trigeminal Nucleus, Spinal / metabolism*


  • Cd53 protein, rat
  • Cytokines
  • Excitatory Amino Acid Transporter 1
  • Proteins
  • Slc1a3 protein, rat
  • Tetraspanin 25
  • Freund's Adjuvant
  • Dual Specificity Phosphatase 1
  • Dusp1 protein, rat
  • Calcitonin Gene-Related Peptide