Chronic Monosodium Glutamate Administration Induced Hyperalgesia in Mice

Nutrients. 2017 Dec 21;10(1):1. doi: 10.3390/nu10010001.


Monosodium glutamate (MSG) is a widely used food additive. Although it is generally considered safe, some questions regarding the impact of its use on general health have arisen. Several reports correlate MSG consumption with a series of unwanted reactions, including headaches and mechanical sensitivity in pericranial muscles. Endogenous glutamate plays a significant role in nociceptive processing, this neurotransmitter being associated with hyperalgesia and central sensitization. One of the mechanisms underlying these phenomena is the stimulation of Ca2+/calmodulin sensitive nitric oxide synthase, and a subsequent increase in nitric oxide production. This molecule is a key player in nociceptive processing, with implications in acute and chronic pain states. Our purpose was to investigate the effect of this food additive on the nociceptive threshold when given orally to mice. Hot-plate and formalin tests were used to assess nociceptive behaviour. We also tried to determine if a correlation between chronic administration of MSG and variations in central nitric oxide (NO) concentration could be established. We found that a dose of 300 mg/kg MSG given for 21 days reduces the pain threshold and is associated with a significant increase in brain NO level. The implications of these findings on food additive-drug interaction, and on pain perception in healthy humans, as well as in those suffering from affections involving chronic pain, are still to be investigated.

Keywords: formalin test; hot-plate test; hyperalgesia; monosodium glutamate; nitric oxide synthase.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Flavoring Agents / administration & dosage
  • Flavoring Agents / toxicity*
  • Formaldehyde
  • Hot Temperature
  • Hyperalgesia / chemically induced*
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology
  • Hyperalgesia / psychology
  • Male
  • Mice
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Nociceptive Pain / chemically induced*
  • Nociceptive Pain / metabolism
  • Nociceptive Pain / physiopathology
  • Nociceptive Pain / psychology
  • Pain Threshold / drug effects*
  • Reaction Time / drug effects
  • Sodium Glutamate / administration & dosage
  • Sodium Glutamate / toxicity*
  • Time Factors


  • Flavoring Agents
  • Formaldehyde
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Sodium Glutamate