PMID- 32796585 OWN - NLM STAT- MEDLINE DCOM- 20210217 LR - 20210217 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 16 DP - 2020 Aug 11 TI - Comparing Gene Expression in the Parabrachial and Amygdala of Diestrus and Proestrus Female Rats after Orofacial Varicella Zoster Injection. LID - 10.3390/ijms21165749 [doi] LID - 5749 AB - The orofacial pain pathway projects to the parabrachial and amygdala, and sex steroids have been shown to affect neuronal activity in these regions. GABA positive cells in the amygdala are influenced by sex steroid metabolites to affect pain, and sex steroids have been shown to alter the expression of genes in the parabrachial, changing neuronal excitability. Mechanisms by which sex steroids affect amygdala and parabrachial signaling are unclear. The expression of genes in the parabrachial and amygdala in diestrus (low estradiol) and proestrus (high estradiol) female rats were evaluated in this study. First, varicella zoster virus was injected into the whisker pad of female rats to induce a pain response. Second, gene expression was quantitated using RNA-seq one week after injection. Genes that had the greatest change in expression and known to function in pain signaling were selected for the quantitation of protein content. Protein expression of four genes in the parabrachial and seven genes in the amygdala were quantitated by ELISA. In the parabrachial, neurexin 3 (Nrnx3) was elevated at proestrus. Nrnx3 has a role in AMPA receptor and GABA signaling. Neuronatin (Nnat) and protein phosphatase, Mg(2+)/Mn(2+) dependent 1E (Ppm1e) were elevated in the parabrachial of diestrus animals both genes having a role in pain signaling. Epoxide hydroxylase (Ephx2) was elevated in the parabrachial at proestrus and the vitamin D receptor (Vdr) was elevated in the amygdala. Ephx2 antagonists and vitamin D have been used to treat neuropathic pain. In conclusion, sex steroids regulate genes in the parabrachial and amygdala that might result in the greater pain response observed during diestrus. FAU - Hornung, Rebecca AU - Hornung R AUID- ORCID: 0000-0002-7629-8144 AD - Department of Biological Sciences, Texas A&M University College of Dentistry, Dallas, TX 75246, USA. FAU - Pritchard, Addison AU - Pritchard A AD - Department of Biological Sciences, Texas A&M University College of Dentistry, Dallas, TX 75246, USA. FAU - Kinchington, Paul R AU - Kinchington PR AUID- ORCID: 0000-0002-1901-9970 AD - Departments of Ophthalmology and Molecular Microbiology and Genetics, University of Pittsburgh, 203 Lothrop Street, Pittsburgh, PA 15213, USA. FAU - Kramer, Phillip R AU - Kramer PR AUID- ORCID: 0000-0003-0117-542X AD - Department of Biological Sciences, Texas A&M University College of Dentistry, Dallas, TX 75246, USA. LA - eng GR - NS064022/NS/NINDS NIH HHS/United States GR - R01 DE026749/DE/NIDCR NIH HHS/United States GR - EY08098/EY/NEI NIH HHS/United States GR - DE026749/DE/NIDCR NIH HHS/United States GR - P30 EY008098/EY/NEI NIH HHS/United States GR - R01 NS064022/NS/NINDS NIH HHS/United States PT - Comparative Study PT - Journal Article DEP - 20200811 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Calcitriol) RN - EC 3.3.2.- (Epoxide Hydrolases) RN - EC 3.3.2.10 (EPHX2 protein, rat) SB - IM MH - Amygdala/*metabolism MH - Animals MH - Diestrus/*genetics MH - Epoxide Hydrolases/metabolism MH - Female MH - *Gene Expression Regulation MH - Herpesvirus 3, Human/*physiology MH - *Injections MH - Nerve Tissue Proteins/metabolism MH - Neuralgia/genetics MH - Proestrus/*genetics MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Receptors, Calcitriol/metabolism PMC - PMC7461146 OTO - NOTNLM OT - herpes zoster OT - orofacial OT - pain OT - shingles OT - steroids COIS- The authors declare no conflict of interest. EDAT- 2020/08/17 06:00 MHDA- 2021/02/18 06:00 PMCR- 2020/08/01 CRDT- 2020/08/16 06:00 PHST- 2020/06/29 00:00 [received] PHST- 2020/08/05 00:00 [revised] PHST- 2020/08/09 00:00 [accepted] PHST- 2020/08/16 06:00 [entrez] PHST- 2020/08/17 06:00 [pubmed] PHST- 2021/02/18 06:00 [medline] PHST- 2020/08/01 00:00 [pmc-release] AID - ijms21165749 [pii] AID - ijms-21-05749 [pii] AID - 10.3390/ijms21165749 [doi] PST - epublish SO - Int J Mol Sci. 2020 Aug 11;21(16):5749. doi: 10.3390/ijms21165749.