- Involvement of chemokine CXCL11 in the development of morphine tolerance in rats with cancer-induced bone pain. [Journal Article]
- JNJ Neurochem 2016 Dec 07
- Morphine is viewed as one of the classical treatments for intractable pain, but its role is limited by side effects, including analgesic tolerance. A few chemokines have been reported to be engaged i...
Morphine is viewed as one of the classical treatments for intractable pain, but its role is limited by side effects, including analgesic tolerance. A few chemokines have been reported to be engaged in the mechanisms of morphine tolerance. However, the exact roles of CXCL11 in chronic morphine tolerance remain unknown. In this study, Walker 256 mammary gland carcinoma cells were inoculated into the tibia of rats to provoke cancer-induced bone pain (CIBP). Then morphine was intrathecally administered twice daily for 7 consecutive days to induce drug tolerance. We found that the level of CXCL11 in lumbar spinal cord was increased during the development of morphine tolerance in CIBP rats. Meanwhile, CXCL11 was co-localized with markers of astrocytes and neurons in the spinal cord. Inhibition of CXCL11 by neutralizing antibodies could remarkably attenuate the degree of morphine tolerance and decrease the activation of astrocytes. Moreover, blocking astrocyte activation by D, L-Fluorocitric acid could distinctly alleviate morphine tolerance and reduce the expression of CXCL11. Finally, morphine stimulation could induce the release of CXCL11 by cultured astrocytes and neurons in vitro. In summary, our results provide evidence that spinal CXCL11 plays a powerful modulatory role in the development of morphine tolerance through cross-talking between astrocytes and neurons. This article is protected by copyright. All rights reserved.
- Pentoxifylline besides naltrexone recovers morphine-induced inflammation in male reproductive system of rats by regulating Toll-like receptor pathway. [Journal Article]
- AAndrologia 2016 Dec 07
- This study aimed to investigate the effect of pentoxifylline on complications of prolonged usage of morphine upon the testis and sperm parameters of rats. In this study, forty male Wistar rats were d...
This study aimed to investigate the effect of pentoxifylline on complications of prolonged usage of morphine upon the testis and sperm parameters of rats. In this study, forty male Wistar rats were divided into five groups (n = 8) and treated for 56 days to only saline, only morphine, only pentoxifylline, pentoxifylline + morphine and naltrexone + morphine. The diameters of seminiferous tubules, the maturity of germ line epithelium and sperm parameters were evaluated. The expression of inflammatory-related factors in testis tissues were also investigated at gene and protein levels. The data were calculated by one-way ANOVA test followed by Tukey's post hoc test using SPSS software for windows (version 20). Seminiferous tubule diameter, the maturity of spermatogonia and sperm parameters were significantly decreased in morphine group in comparison with control, pentoxifylline and pentoxifylline + morphine groups (p < .001). The expression of anti-inflammatory markers, at both gene and protein levels, was significantly increased in testis of morphine-treated rats in comparison with other groups (p < .001). Chronic morphine administration induces destructive effects on male reproductive system by regulating inflammatory responses. Pentoxifylline recovers the destructive effects of morphine on male reproductive system by inhibiting TLR (Toll-like receptor) activity, as an anti-inflammatory response.
- Physiologically-Based Pharmacokinetic Modeling Revealed Minimal Codeine Intestinal Metabolism in First-Pass Removal in Rats. [Journal Article]
- BDBiopharm Drug Dispos 2016 Dec 07
- The physiologically-based model with segregated flow to the intestine (SFM-PBPK; partial, lower flow to enterocyte region vs. greater flow to serosal region) was found to describe first-pass glucuron...
The physiologically-based model with segregated flow to the intestine (SFM-PBPK; partial, lower flow to enterocyte region vs. greater flow to serosal region) was found to describe first-pass glucuronidation of morphine (M) to morphine-3β-glucuronide (MG) in rats after intraduodenal (ID) and intravenous (IV) administration better than the traditional model (TM), for which a single intestinal flow perfused the whole of the intestinal tissue. The SFM described a greater extent of intestinal M glucuronidation for ID vs. IV administration. We presently applied the same PBPK modeling approaches to examine the contributions of the intestine and liver on first-pass metabolism of the precursor, codeine (C, 3-methylmorphine) in the rat. Unexpectedly, profiles of C, M, and MG in whole blood, bile and urine, assayed by LCMS, were equally well described by both the TM-PBPK and SFM-PBPK. The fitted parameters for the models were similar, and the net formation intrinsic clearance of M (from C) for the liver was much higher, being 9- to 13-fold that of the intestine. Simulations, based on absence of intestinal formation of M, correlated well with observations. The lack of discrimination of SFM and TM with the codeine data did not invalidate the SFM-PBPK model but rather suggests that the liver is the only major organ for C metabolism. Because of little or no contribution by the intestine to the metabolism of C, both the TM- and SFM-PBPK models are equally consistent with the data.
- Combined femoral and sciatic nerve block versus femoral and local infiltration anesthesia for pain control after total knee arthroplasty: a meta-analysis of randomized controlled trials. [Journal Article]
- JOJ Orthop Surg Res 2016 Dec 07; 11(1):158
- CONCLUSIONS: SNB may provide earlier anesthesia effects than LIA when combined femoral nerve block (FNB); however, there were no differences in morphine use, active knee flexion, and PONV between the groups. The LIA group spent less time under anesthesia, suggesting that LIA may offer a practical and potentially safer alternative to SNB.
- Pain Treatment Continues To Be Inaccessible for Many Patients Around the Globe: Second Phase of Opioid Price Watch, a Cross-Sectional Study To Monitor the Prices of Opioids. [Journal Article]
- JPJ Palliat Med 2016 Dec 06
- CONCLUSIONS: Patients in LIC and MIC have less access to opioid medications. This highlights the need to continue efforts at improving access, availability, and affordability.
- A Prospective Randomized Comparative Trial of Targeted Steroid Injection Via Epidural Catheter Versus Standard C7-T1 Interlaminar Approach for the Treatment of Unilateral Cervical Radicular Pain. [Journal Article]
- RAReg Anesth Pain Med 2016 Dec 05
- CONCLUSIONS: This trial showed no significant difference in clinical outcomes with CIESI using a targeted epidural catheter compared to a standard C7-T1 approach for the treatment of unilateral cervical radicular pain at the C5 or C6 level. Both techniques were associated with clinically meaningful improvement across outcome domains of pain, function, disability, and medication use. These effects persisted to 6-month follow-up.The study was registered at Clinical Trials.gov (NCT02095197).
- Fluoroscopic Guidance Increases the Incidence of Thoracic Epidural Catheter Placement Within the Epidural Space: A Randomized Trial. [Journal Article]
- RAReg Anesth Pain Med 2016 Dec 05
- CONCLUSIONS: Fluoroscopic guidance increases the incidence of epidural catheter positioning within the epidural space and may reduce postanesthesia care unit and hospital lengths of stay. Future work should validate the effectiveness of this approach.This clinical trial is registered with ClinicalTrials.gov (NCT02678039).
- Comparison of Abuse, Suspected Suicidal Intent, and Fatalities related to the 7-day Buprenorphine Transdermal Patch versus other Opioid Analgesics in the National Poison Data System. [Journal Article]
- PMPostgrad Med 2016 Dec 06
- CONCLUSIONS: This post-marketing evaluation of BTDS indicates infrequent poison center calls for intentional abuse and suspected suicidal intent events, suggesting lower rates of these risks with BTDS compared to other ER/LA opioids.
- Memories of Opiate Withdrawal Emotional States Correlate with Specific Gamma Oscillations in the Nucleus Accumbens. [Journal Article]
- NNeuropsychopharmacology 2016 Dec 06
- Affective memories associated with the negative emotional state experienced during opiate withdrawal are central in maintaining drug-taking, seeking and relapse. Nucleus accumbens (NAC) is a key stru...
Affective memories associated with the negative emotional state experienced during opiate withdrawal are central in maintaining drug-taking, seeking and relapse. Nucleus accumbens (NAC) is a key structure both for acute withdrawal and withdrawal memories reactivation, however NAC neuron coding properties underpinning the expression of these memories remain largely unknown. Here we aimed at deciphering the role of NAC neurons in the encoding and retrieval of opiate withdrawal memory. Chronic single neuron and local field potentials recordings were performed in morphine-dependent rats and placebo-controls. Animals were subjected to an unbiased conditioned placed aversion protocol with one compartment (CS+) paired with naloxone-precipitated withdrawal, a second compartment with saline injection (CS-) and a third being neutral (no pairing). After conditioning, animals displayed a typical place aversion for CS+ and developed a preference for CS- characteristic of safety learning. We found that distinct NAC neurons code for CS+ or CS-. Both populations also displayed highly specific oscillatory dynamics, CS+ and CS- neurons respectively following 80 Hz (G80) and 60 Hz (G60) local field potential gamma rhythms. Finally, we found that the balance between G60 and G80 rhythms strongly correlated both with the ongoing behavior of the animal as well as the strength of the conditioning. We demonstrate here that the aversive and preferred environments are underpinned by distinct groups of NAC neurons as well as specific oscillatory dynamics. This suggest that G60/G80 interplay-established through the conditioning process- serves as a robust and versatile mechanism for a fine coding of the environment emotional weight.Neuropsychopharmacology accepted article preview online, 06 December 2016. doi:10.1038/npp.2016.272.
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- miR-365 targets β-arrestin 2 to reverse morphine tolerance in rats. [Journal Article]
- SRSci Rep 2016 Dec 06; 6:38285
- Morphine tolerance is a challenging clinical problem that limits its clinical application in pain treatment. Non-coding microRNAs (miRNAs) modulate gene expression in a post transcriptional manner, a...
Morphine tolerance is a challenging clinical problem that limits its clinical application in pain treatment. Non-coding microRNAs (miRNAs) modulate gene expression in a post transcriptional manner, and their dysregulation causes various diseases. However, the significance of miRNAs in morphine tolerance is still poorly understood. In the present study, we hypothesized that microRNA-365 (miR-365) is a key functional small RNA that reverses morphine tolerance through regulation of β-arrestin 2 in rats. Here, microarray analysis and quantitative real-time PCR showed that miR-365 was robustly decreased in the spinal cord after chronic morphine administration. In situ hybridization and immunochemistry double staining showed that miR-365 was expressed in neurons of the spinal cord. We identified β-arrestin 2 as the target gene of miR-365 by bioinformatics analysis and luciferase reporter assay. The data showed that overexpression of miR-365 prevented and reversed established morphine tolerance, and increased expression of miR-365 caused a decrease in expression of β-arrestin 2 protein. miR-365 downregulation is involved in the development and maintenance of morphine tolerance through regulation of β-arrestin 2, and miR-365 upregulation provides a promising and novel approach for treatment of morphine tolerance.