Intravenous valproate inhibits ongoing and evoked activity of dura-sensitive thalamic neurons in rats

• Published in: European journal of pharmacology 2013-09, Vol.715 (1-3), p.204-211
• Main Authors: Sokolov, Alexey Y., Lyubashina, Olga A., Sivachenko, Ivan B., Berkovich, Regina R., Panteleev, Sergey S.
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; anesthesia; Animals; cortex; Dose-Response Relationship, Drug; Dura Mater; Dural electrical stimulation; Electric Stimulation; electrical treatment; Evoked Potentials - drug effects; headache; intravenous injection; longevity; Male; Migraine; Neuronal activity; neurons; Neurons - cytology; Neurons - drug effects; pharmacology; Rats; Rats, Wistar; sodium; Thalamus; Thalamus - cytology; Trigemino-vascular system; Valproate; Valproic Acid - administration & dosage; Valproic Acid - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2013.05.019

Valproate is widely used for migraine treatments, although precise mechanisms of its anticephalgic action are poorly understood. Migraine attacks are thought to occur due to trigemino-vascular system activation, which in turn, stimulates nociceptive transmission in trigemino-thalamo-cortical pathway. The ventroposteromedial (VPM) nucleus of the thalamus is considered to play a prominent role in neurobiology of headaches by serving as the highest subcortical relay for conveying nociceptive information from intra- and extra-cranial structures to the cortex. While it has been demonstrated that valproate can modulate trigemino-vascular nociceptive neurotransmission in the VPM, its effects have been investigated using only intrathalamic ejection of the compound in pentobarbitone sodium anesthetized rats. The objective of our study was to evaluate the effects of intravenously administered valproate on both ongoing firing of the VPM neurons and their activity induced by electrical stimulation of the dura mater. The experiments were performed on rats under nonbarbiturate anesthesia. To define the dose-dependent properties and longevity of the studied effects of valproate, two distinguished dosing regiments were used: bolus (single infusion at a dose of 300mg/kg) and cumulative (thrice-repeated administration of 100mg/kg performed 30min apart). Intravenous administration of valproate produced the dose-dependent suppression of both the ongoing activity of the thalamic VPM neurons and their responses to electrical stimulation of the dura mater. This effect was fast-developing (within 5min) and short-lasting (no longer than 30min). These data suggest that intravenous administration of valproate could produce a reduction of the thalamo-cortical nociceptive transmission associated with trigemino-vascular activation.