Honokiol for the Treatment of Neonatal Pain and Prevention of Consequent Neurobehavioral Disorders

• Type of Material: Article
• Authors: Anna Woodbury, Emory University; Shan Ping Yu, Emory University; Dongdong Chen, Emory University; Xiaohuan Gu, Emory University; Jin Hwan Lee, Emory University; James Zhang, Emory University; Alyssa Espinera, Emory University; Paul Garcia, Emory University; Ling Wei, Emory University
• Language: English
• Date: 2015-11-01
• Publisher: American Chemical Society
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 American Chemical Society and American Society of Pharmacognosy.
• Final Published Version (URL): http://dx.doi.org/10.1021/acs.jnatprod.5b00225
• Title of Journal or Parent Work: Journal of Natural Products
• ISSN: 0163-3864
• Volume: 78
• Issue: 11
• Start Page: 2531
• End Page: 2536
• Grant/Funding Information: This work was supported by a Foundation for Anesthesia Education and Research (FAER) Research Fellowship grant (A.W.), NIH grants NS075338 (L.W.), NS062097 (L.W.), and NS0458710 (S.P.Y.), an AHA Established Investigator Award (L.W.), and an AHA Grant-in-Aid grant 12GRNT12060222 (S.P.Y.).
• Keywords: BRADYKININ; GENE-EXPRESSION; Chemistry, Medicinal; Science & Technology; FORMALIN; NEUROKININ-1 RECEPTORS; INFLAMMATORY PAIN; NATURAL-PRODUCTS MAGNOLOL; Pharmacology & Pharmacy; MORPHINE; SUBSTANCE-P; Life Sciences & Biomedicine; GLUTAMATE; KAPPA-B ACTIVATION; Plant Sciences
• Research Categories: Health Sciences, Pharmacology; Biology, Neuroscience

Abstract

This study examined the short- and long-term neuroprotective and analgesic activity of honokiol (a naturally occurring lignan isolated from Magnolia) on developing brains in neonates exposed to inflammatory pain, known to cause neuronal cell death. Postnatal day 4 (P4) neonatal rat pups were subjected to intraplantar formalin injection to four paws as a model of severe neonatal pain. Intraperitoneal honokiol (10 mg/kg) or corn oil vehicle control was administered 1 h prior to formalin insult, and animals were maintained on honokiol through postnatal day 21 (P21). Behavioral tests for stress and pain were performed after the painful insult, followed by morphological examinations of the brain sections at P7 and P21. Honokiol significantly attenuated acute pain responses 30 min following formalin insult and decreased chronic thermal hyperalgesia later in life. Honokiol-treated rats performed better on tests of exploratory behavior and performed significantly better in tests of memory. Honokiol treatment normalized hippocampal and thalamic c-Fos and hippocampal alveus substance P receptor expression relative to controls at P21. Together, these findings support that (1) neonatal pain experiences predispose rats to the development of chronic behavioral changes and (2) honokiol prevents and reduces both acute and chronic pathological pain-induced deteriorations in neonatal rats.