Systemic administration of monosodium glutamate induces sexually dimorphic headache- and nausea-like behaviours in rats

Abstract

Ingestion of monosodium glutamate (MSG) causes headache, nausea, and craniofacial tenderness in healthy individuals. The present study explored whether MSG produces behavioural signs of headache, nausea, and changes in craniofacial sensitivity in rats. The behavior of male and female Sprague-Dawley rats was video recorded before and after intraperitoneal (i.p.) injections of MSG (1-1000 mg/kg), nitroglycerin (GTN, 10 mg/kg), or normal saline. Behaviors (grimace score, head-flicks, rearing, head scratches, facial grooming, lying-on-belly, and temporalis muscle region mechanical withdrawal threshold) were evaluated. Facial cutaneous temperature of the nose and forehead was measured before and after i.p. injections via infrared thermography. Plasma glutamate and calcitonin gene-related peptide concentrations after administration of 1000 mg/kg MSG were measured in anesthetized rats. Monosodium glutamate induced nocifensive, headache-like, and nausea-like behaviors in a dose-related manner but had no effect on mechanical threshold. Monosodium glutamate (1000 mg/kg) induced a significantly greater frequency of headache-like behavior in females but a longer duration of nausea-like behavior in males. Monosodium glutamate produced a prolonged increase in plasma glutamate and calcitonin gene-related peptide concentrations. Co-administration of the median effective dose of MSG (350 mg/kg) with GTN (10 mg/kg) amplified headache-like behaviors, induced significant craniofacial sensitivity, and produced increased nausea-like behaviour. Co-administration of sumatriptan or naproxen with MSG (1000 mg/kg) significantly attenuated MSG-induced nocifensive and headache-like behaviors. Our data suggest that systemic administration of MSG to rats induces behavioral correlates of headache and nausea. This model may offer another avenue for research on the mechanism and treatment of primary headache disorders such as migraine.

Peripheral N-methyl-d-aspartate receptor activation contributes to monosodium glutamate-induced headache but not nausea behaviours in rats

“…3 a). Consistent with our previous results, males were found to exhibit a substantially greater increase in LOB duration compared to females 7 . In females, there was no significant effect of MSG treatment on LOB behaviour (Fig.…”

“…We have previously found that MSG (1000 mg/kg, i.p.) significantly suppresses normal exploratory and grooming (facial grooming and head scratch) behaviours compared to saline control 7 . There was a significant effect of time (F (4.510, 297.7) = 3.088; p = 0.0126), but no significant effect of treatment (F (5, 66) = 1.365; p = 0.2487) or time/treatment interaction (F (25, 330) = 0.9124; p = 0.5883) for facial grooming behaviour (Fig.…”

“…Specifically, intraperitoneal injections (i.p.) of 1000 mg/kg MSG significantly increased nocifensive and headache-like behaviours compared to control (saline), which are attenuated by administration of the migraine abortive therapy sumatriptan 7 . In addition, this dose of MSG produces behavioural and physiological signs of nausea in rats.…”

“…In addition, this dose of MSG produces behavioural and physiological signs of nausea in rats. Headache-like and nausea behaviours occur in association with an increase in plasma glutamate and calcitonin-gene related peptide (CGRP) concentrations, supporting the notion that peripheral glutamate receptor activation may directly or indirectly (through CGRP-mediated mechanisms) contribute to headache pathogenesis 1 , 7 . Nevertheless, the specific excitatory amino acid receptors through which peripheral glutamate contributes to headache generation in this model have not been identified.…”

“…We have developed an in vivo rat model, which uses systemic administration of MSG to induce headache-like and nausea behaviours 7 . This model produces dose- and time-dependent increases in nocifensive and headache-like behaviours in a sexually dimorphic fashion.…”