Microinjection of valproic acid into the ventrolateral orbital cortex exerts an antinociceptive effect in a rat of neuropathic pain.

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  • Additional Information
    • Source:
      Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 7608025 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-2072 (Electronic) Linking ISSN: 00333158 NLM ISO Abbreviation: Psychopharmacology (Berl) Subsets: MEDLINE
    • Publication Information:
      Original Publication: Berlin, New York, Springer-Verlag.
    • Subject Terms:
      Disease Models, Animal*; Analgesics/*administration & dosage ; GABA Agents/*administration & dosage ; Neuralgia/*drug therapy ; Prefrontal Cortex/*drug effects ; Valproic Acid/*administration & dosage; Animals ; Dose-Response Relationship, Drug ; Male ; Microinjections/methods ; Neuralgia/metabolism ; Prefrontal Cortex/metabolism ; Rats ; Rats, Sprague-Dawley
    • Abstract:
      Rationale: Ventrolateral orbital cortex (VLO) has been found to play an important role in the regulation of neuropathic pain (NPP). As a traditional mood stabilizer, valproic acid (VPA) is currently employed in the treatment of NPP. However, whether VPA plays an analgesic role in VLO is still unknown.
      Objectives: To elucidate the underlying analgesic mechanism of microinjection of VPA into the VLO on spared nerve injury (SNI), an animal model of NPP.
      Methods: We firstly examined the role of VPA by intraperitoneal and intral-VLO injection. Then, we accessed its role as a histone deacetylase inhibitor by intral-VLO microinjection of sodium butyrate. Finally, the GABAergic mechanism was measured through the intra-VLO microinjection of several agonists and antagonists of various GABAergic receptor subtypes.
      Results: Both intraperitoneal and intral-VLO injection of VPA attenuated SNI-induced mechanical allodynia. Microinjection of sodium butyrate, one of the histone deacetylase inhibitors, into the VLO attenuated the mechanical allodynia. Besides, microinjection of valpromide, a derivative of VPA which is a GABAergic agonist, into the VLO also attenuated allodynia. Furthermore, microinjection of picrotoxin, a GABAA receptor antagonist, into the VLO attenuated mechanical allodynia; microinjection of picrotoxin before VPA into the VLO increased VPA-induced anti-allodynia. Besides, microinjection of CGP 35348, a GABAB receptor antagonist, into the VLO attenuated allodynia; microinjection of CGP 35348 before VPA into the VLO also increased VPA-induced anti-allodynia. What is more, microinjection of imidazole-4-acetic acid (I4AA), a GABAC receptor antagonist, into the VLO enhanced allodynia; microinjection of I4AA before VPA into the VLO decreased VPA-induced anti-allodynia.
      Conclusions: These results suggest that both the histone acetylation mechanism and GABAergic system are involved in mediating VLO-induced anti-hypersensitivity.
    • Grant Information:
      81771435 National Natural Science Foundation of China (CN); SKLMS 2017002) Research Project of State Key Laboratory for Manufacturing Systems Engineering; 2016JM8078 Natural Science Basic Research Plan in Shaanxi Province of China
    • Contributed Indexing:
      Keywords: GABAergic modulation; Histone deacetylase inhibitor; Neuropathic pain; Valproic acid; Ventrolateral orbital cortex
    • Accession Number:
      0 (Analgesics)
      0 (GABA Agents)
      614OI1Z5WI (Valproic Acid)
    • Publication Date:
      Date Created: 20200530 Date Completed: 20201110 Latest Revision: 20201110
    • Publication Date:
      20231215
    • Accession Number:
      10.1007/s00213-020-05551-7
    • Accession Number:
      32468099