Treatment of child victims of abuse and neglect

This publication reviews the effects of and treatment for various types of child victimization experiences. It will be helpful to child protection workers, guardians ad litem, attorneys, family court judges, and others involved with children who have been abused or neglected. This information will enhance the ability of child protection professionals to recognize a need for mental health treatment and to seek appropriate treatment services. This publication will also enable other professionals to better communicate with therapists about a child’s needs and progress

Evidence that opioids may have toll-like receptor 4 and MD-2 effects

Opioid-induced proinflammatory glial activation modulates wide-ranging aspects of opioid pharmacology including: opposition of acute and chronic opioid analgesia, opioid analgesic tolerance, opioid-induced hyperalgesia, development of opioid dependence, opioid reward, and opioid respiratory depression. However, the mechanism(s) contributing to opioid-induced proinflammatory actions remains unresolved. The potential involvement of toll-like receptor 4 (TLR4) was examined using in vitro, in vivo, and in silico techniques. Morphine non-stereoselectively induced TLR4 signaling in vitro, blocked by a classical TLR4 antagonist and non-stereoselectively by naloxone. Pharmacological blockade of TLR4 signaling in vivo potentiated acute intrathecal morphine analgesia, attenuated development of analgesic tolerance, hyperalgesia, and opioid withdrawal behaviors. TLR4 opposition to opioid actions was supported by morphine treatment of TLR4 knockout mice, which revealed a significant threefold leftward shift in the analgesia dose response function, versus wildtype mice. A range of structurally diverse clinically-employed opioid analgesics was found to be capable of activating TLR4 signaling in vitro. Selectivity in the response was identified since morphine-3-glucuronide, a morphine metabolite with no opioid receptor activity, displayed significant TLR4 activity, whilst the opioid receptor active metabolite, morphine-6-glucuronide, was devoid of such properties. In silico docking simulations revealed ligands bound preferentially to the LPS binding pocket of MD-2 rather than TLR4. An in silico to in vitro prediction model was built and tested with substantial accuracy. These data provide evidence that select opioids may non-stereoselectively influence TLR4 signaling and have behavioral consequences resulting, in part, via TLR4 signaling.Mark R. Hutchinson, Yingning Zhang, Mitesh Shridhar, John H. Evans, Madison M. Buchanan, Tina X. Zhao, Peter F. Slivka, Benjamen D. Coats, Niloofar Rezvani, Julie Wieseler, Travis S. Hughes, Kyle E. Landgraf, Stefanie Chan, Stephanie Fong, Simon Phipps, Joseph J. Falke, Leslie A. Leinwand, Steven F. Maier, Hang Yin, Kenner C. Rice and Linda R. Watkinshttp://www.elsevier.com/wps/find/journaldescription.cws_home/622800/description#descriptio