Attenuation of opioid addiction in mice lacking aquaporin 4

OBJECTIVE To examine the effects of aquaporin 4(AQP4) on opioid addiction and underlie the mechanism behind it. METHODS(1) In the heroin-induced self-administration(SA) experiment,we explored the role of AQP4 on heroin-induced psychological addiction. After the mice were trained to learn heroin-induced SA under a fixedratio1(FR1) reinforcement program for 7 d,we randomly switched the heroin doses to 0.00625,0.0125,0.025,0.05 or 0.1 mg·kg^(-1)per infusion to counterbalance assignment design. In the end,all mice underwent extinction training and reinstatement testing.(2) In oral sucrose self-administration,5% sucrose solution was used for the mice and the procedures were similar to heroin SA.(3) In morphine-induced hyperactivity test,mice were habituated in the test apparatus for 30 min and then were given saline(10 mL·kg^(-1),sc) or morphine(10 or 20 mg·kg^(-1),sc) to record the locomotion for 1.5 h.(4) For the in vivo microdialysis experiment,mice were surgically implanted with intracranial guide cannula into nucleus accumbens(AP +1.4 mm,ML ±0.9 mm,DV-3.8 mm from bregma). After 5 d of recovery from surgery,the mice were challenged by saline(10 mL·kg^(-1),sc)or morphine(10 mg·kg^(-1),sc),and then samples were collected every 20 min. RESULTS We found that AQP4 deletion had no effects on sucrose-seeking and sucrose-taking,but it significantly attenuated heroin-taking and heroin-seeking behaviors in heroin self-administration. Besides these,AQP4 deletion had no effects on basal level of locomotion,but dramatically decreased morphine-induced hyperactivity.Furthermore,the in vivo microdialysis studies showed that AQP4 deficiency inhibited morphine(10mg · kg^(-1),sc)-induced elevation of extracellular dopamine levels in nucleus accumbens in mice.CONCLUSION Our present findings demonstrate that AQP4 was potentially involved in the properties of opioid rewarding by inhibiting dopamine release in nucleus accumbens(NAc).

Comparison between intravenous morphine versus fentanyl in acute pain relief in drug abusers with acute limb traumatic injury

BACKGROUND: Rapid and effective pain relief in acute traumatic limb injuries(ATLI) is one of the most important roles of emergency physicians. In these situations, opioid addiction is an important concern because of the dependency on opioids. The study aims to compare the effectiveness of intravenous(IV) fentanyl versus morphine in reducing pain in patients with opioid addiction who suffered from ATLI.METHODS: In this double-blind randomized clinical trial, 320 patients with ATLI, who presented to the emergency department(ED) from February 2016 to April 2016, were randomly divided into two groups. One group(160 patients) received 0.1 mg/kg IV morphine. The other group(160 patients) received 1 mcg/kg IV fentanyl. Patients' demographic data, pain score at specif ic intervals, vital signs, side effects, satisfaction and the need for rescue analgesia were recorded.RESULTS: Eight patients in the morphine group and five patients in the fentanyl group were excluded. Pain score in the fentanyl group had a significant decrease at 5-minute follow-up(P value=0.00). However, at 10, 30, and 60-minute follow-ups no signifi cant differences were observed between the two groups in terms of pain score reduction. The rescue analgesia was required in 12(7.7%) patients in the fentanyl group and in 48(31.6%) patients in the morphine group(P value=0.00). No signifi cant difference was observed regarding side effects, vital signs and patients' satisfaction between the two groups.CONCLUSION: Fentanyl might be an effective and safe drug in opioid addicts suffering from ATLI.

Efficacy of Perioperative Intravenous Lidocaine for Multimodal Analgesia

Given the rising incidence of opioid misuse and opioid-related deaths worldwide, it is imperative to find nonopioid analgesic adjuncts for perioperative pain management. Perioperative opioid exposure in opioid-naïve patients for even minor surgical procedures may result in significant opioid dependence. Although the use of intravenous lidocaine in the perioperative period is not novel, recently it has been proposed as an important adjunct to multimodal analgesia. In addition to improving acute pain, lidocaine may reduce the incidence of chronic post-operative pain syndrome (CPPS), improve bowel function, and decrease post-operative nausea and vomiting (PONV) thereby speeding up the post-operative recovery process. Furthermore, lidocaine has efficacy in a variety of procedures including abdominal, gynecological, and urological surgeries. The aim of this narrative review is to evaluate the effects of intravenous lidocaine compared to traditional analgesic methods on post-operative pain control and recovery for various surgical procedures.

Acupuncture and the Opioid Epidemic in America

The opioid epidemic has become a significant public health crisis in the United States of America. This crisis has elicited a response at high levels of governmental and health care organizations including the American College of Physicians, the Food and Drug Administration, the Joint Commission, the National Academies of Science, Engineering and Medicine, the National Association of Attorneys General, and the White House. In various ways, these organizations have recognized that acupuncture can play an important role in dealing with the opioid epidemic. This paper presents and analyzes the scientific evidence supporting the efficacy of acupuncture in regard to opioid addiction.

Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats

Abstract Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hip- pocampal extracellular glutamate level induced by nalox- one （2 mg/kg, i.p.） precipitation. Agmatine （20 mg/kg, s.c.） administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synapto- somes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agrnatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors （NMDARs） was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine pre- vented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including mod- ulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.