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Opioid Induces Hyperalgesia

Michelle Hook, Sarah Woller, Eric Bancroft, Miriam Aceves, Mary Katherine Funk, John Hartman, Sandra M Garraway
Opioids and NSAIDs are commonly used to manage pain in the early phase of spinal cord injury (SCI). Despite its analgesic efficacy, however, our studies suggest that intrathecal (i.t.) morphine undermines locomotor recovery and increases lesion size in a rodent model of SCI. Similarly, intravenous (i.v.) morphine attenuates locomotor recovery. The current study explores whether i.v. morphine also increases lesion size after a spinal contusion (T12) injury, and quantifies the cell types that are affected by early opioid administration...
October 20, 2016: Journal of Neurotrauma
Teng-Fei Li, Nian Gong, Yong-Xiang Wang
Aconitines, including bulleyaconitine A, probably the most bioactive and abundant alkaloids in Aconitum plant, are a group of diester C19-diterpenoid alkaloids with one acetylester group attached to C8 of the diterpenoid skeleton and one benzoylester group to C14. Hydrolysis of both groups is involved in the processing of Aconitum, a traditional Chinese medicinal approach. We recently demonstrated that bulleyaconitine A produced anti-hypersensitivity, which was mediated by stimulation of spinal microglial dynorphin A expression...
2016: Frontiers in Pharmacology
Georges Daccache, Edouard Caspersen, Michel Pegoix, Kelly Monthé-Sagan, Ludovic Berger, Dominique Fletcher, Jean-Luc Hanouz
BACKGROUND: The intraoperative modulation of opioids continues to be based on clinical signs. This may result in adverse events such as sympathetic reactivity or opioid induced hyperalgesia. Recently, the Analgesia/Nociception Index (ANI), a non-invasive 0-100 index derived from heart rate variability analysis, has been proposed for nociception assessment. However, the ability of the ANI to adequately guide intraoperative opioid administration has never been demonstrated. We designed a prospective study to evaluate the ability of the ANI to guide remifentanil administration in vascular surgery...
October 12, 2016: Anaesthesia, Critical Care & Pain Medicine
Darakhshan Jabeen Haleem, Shazia Nawaz
: Morphine and other opioids are amongst most effective prescription medications for the treatment of pain. Addiction and hyperalgesia associated with their long-term use, limits the clinical utility of these drugs. In view of a role of somatodendritic serotonin-1A receptors in addiction and analgesic effects of morphine, the present study concerns effects of co-use of buspirone, a partial agonist at serotonin-1A receptor, on reinforcing, hyperalgesic and motor effects of morphine in rats...
October 11, 2016: Journal of Pain: Official Journal of the American Pain Society
E H Y Yu, D H D Tran, S W Lam, M G Irwin
The unique pharmacology of remifentanil makes it a popular intra-operative analgesic. Short-acting opioids like remifentanil have been associated with acute opioid tolerance and/or opioid-induced hyperalgesia, two phenomena which have different mechanisms and are pharmacologically distinct. Clinical studies show heterogeneity of remifentanil infusion regimens, durations of infusion, maintenance of anaesthesia, cumulative dose of remifentanil and pain measures, which makes it difficult to draw conclusions about the incidence of acute tolerance or hyperalgesia...
November 2016: Anaesthesia
Sung Kwan Choi, Myung Ha Yoon, Jung Il Choi, Woong Mo Kim, Bong Ha Heo, Keun Seok Park, Ji A Song
BACKGROUND: Although intraoperative opioids provide more comfortable anesthesia and reduce the use of postoperative analgesics, it may cause opioid induced hyperalgesia (OIH). OIH is an increased pain response to opioids and it may be associated with N-methyl-D-aspartate (NMDA) receptor. This study aimed to determine whether intraoperative nefopam or ketamine, known being related on NMDA receptor, affects postoperative pain and OIH after continuous infusion of intraoperative remifentanil...
October 2016: Korean Journal of Anesthesiology
Zenggui Yu, Weilan Wu, Xiaodan Wu, Hongyi Lei, Cansheng Gong, Shiyuan Xu
High dosages of intra-operative remifentanil are associated with opioid-induced hyperalgesia (OIH). The aim of the present study was to investigate the effect of combined dexmedetomidine and flurbiprofen axetil treatment on remifentanil-induced hyperalgesia. Patients with an American Society of Anesthesiologists physical status of I-II who were diagnosed with hysteromyoma and scheduled for laparoscopic assisted vaginal hysterectomy (LAVH) were randomly divided into three groups. Group hyperalgesia (Group H, n=29) received intra-operative remifentanil, Group hyperalgesia and dexmedetomidine (Group HD, n=28) received remifentanil and a continuous infusion of dexmedetomidine, and Group hyperalgesia, dexmedetomidine and flurbiprofen axetil (Group HDF, n=29) received remifentanil, flurbiprofen axetil and dexmedetomidine...
October 2016: Experimental and Therapeutic Medicine
Wenjuan Tao, Wenjie Zhou, Yuping Wang, Tingting Sun, Haitao Wang, Zhi Zhang, Yan Jin
The efficacy of opioids in patients with chronic neuropathic pain remains controversial. Although activation of δ-opioid receptors (DORs) in the brainstem reduces inflammation-induced persistent hyperalgesia, it is not effective under persistent neuropathic pain conditions and these clinical problems remain largely unknown. In this study, by using a chronic constriction injury (CCI) of the sciatic nerve in rats, we found that in the brainstem nucleus raphe magnus (NRM), DORs emerged on the surface membrane of central synaptic terminals on day 3 after CCI surgery and disappeared on day 14...
September 17, 2016: Neuroscience
Nalini Vadivelu, Erika Schermer, Vijay Kodumudi, Kumar Belani, Richard D Urman, Alan David Kaye
Ketamine an N-methyl-D-aspartate (NMDA) receptor blocking agent and a dissociative anesthetic with neurostimulatory side effects. In recent years, multiple research trials as well as systematic reviews and meta-analyses suggest the usefulness of ketamine as a strong analgesic used in subanesthetic intravenous doses, and also as a sedative. In addition, ketamine was noted to possess properties of anti-tolerance, anti-hyperalgesia and anti-allodynia most likely secondary to inhibition of the NMDA receptors. Tolerance, hyperalgesia and allodynia phenomena are the main components of opioid resistance, and pathological pain is often seen in the clinical conditions involving neuropathic pain, opioid-induced hyperalgesia, and central sensitization with allodynia or hyperalgesia...
July 2016: Journal of Anaesthesiology, Clinical Pharmacology
Isaac J Dripps, Qin Wang, Richard R Neubig, Kenner C Rice, John R Traynor, Emily M Jutkiewicz
RATIONALE: Regulator of G protein signaling (RGS) proteins act as negative modulators of G protein signaling. RGS4 has been shown to negatively modulate G protein signaling mediated by the delta opioid receptor (DOPr) in vitro. However, the role of RGS4 in modulating DOPr-mediated behaviors in vivo has not been elucidated. OBJECTIVE: The aim of this study was to compare the ability of the DOPr agonist SNC80 to induce DOPr-mediated antinociception, antihyperalgesia, antidepressant-like effects, and convulsions in wild-type and RGS4 knockout mice...
September 13, 2016: Psychopharmacology
Sara M Hall, Lindsay LeBaron, Cyf Ramos-Colon, Chaoling Qu, Jennifer Yanhua Xie, Frank Porreca, Josephine Lai, Yeon Sun Lee, Victor J Hruby
Dynorphin A (Dyn A) is a unique endogenous ligand that possesses well-known neuroinhibitory effects via opioid receptors with a preference for the kappa receptor but also neuroexcitatory effects, which cause hyperalgesia. We have shown that the neuroexcitatory effects are mediated through bradykinin (BK) receptors and that intrathecal ( administration of our lead ligand 1, [des-Arg(7)]-Dyn A-(4-11), which shows good binding affinity (IC50 = 150 nM) at the BK receptors, blocks Dyn A-induced hyperalgesia in naïve animals and reverses thermal and tactile hypersensitivities in a dose-dependent manner in nerve-injured animals...
September 27, 2016: ACS Chemical Neuroscience
Gu Gong, Ling Hu, Fuen Qin, Liang Yin, Xiaobo Yi, Libang Yuan, Wei Wu
BACKGROUND: Tremendous experimental and clinical studies identify that remifentanil anesthesia might elicit postoperative opioid-induced hyperalgesia (OIH) and aggravate nociceptive hypersensitivity, whereas definite mechanisms remain equivocal. WNT signaling and fractalkine pathway have been manifested to participate in varieties of pain pathogenesis, respectively, but no report is on whether they could lead to OIH. This study intended to investigate the effect of WNT3a/β-catenin on fractalkine and its receptor CX3CR1 in OIH in rats model of incision pain...
October 28, 2016: Neuroscience Letters
Qian Huang, Xiao-Fang Mao, Hai-Yun Wu, Teng-Fei Li, Ming-Li Sun, Hao Liu, Yong-Xiang Wang
BACKGROUND: Aconiti brachypodi Radix (Xue-shang-yi-zhi-hao) has been prescribed to manage chronic pain, arthritis, and traumatic injuries. Bullatine A, a C20-diterpenoid alkaloid, is one of its principle effective compounds. This study aimed to investigate the anti-hypersensitivity of bullatine A in a variety of rat pain models and explore its mechanisms of action. METHODS: Rat neuropathic pain, inflammatory pain, diabetic neuropathic pain, and bone cancer pain models were used...
2016: Journal of Neuroinflammation
Jianhui Zhao, Hong Wang, Tieying Song, Yunliang Yang, Kunfeng Gu, Pengyu Ma, Zaiwang Zhang, Limin Shen, Jiabao Liu, Wenli Wang
Opioid analgesics have less efficacy in diabetic neuropathy treatment, and tolerance often occurs after chronic usage. Given that thalidomide can potentiate the morphine efficacy in diabetic neuropathy treatment, we investigated the effects of intrathecal administrations of thalidomide on morphine tolerance during the treatment of diabetic neuropathy. We found that intrathecal administrations of thalidomide (25 mg/kg/ml) potentiated the analgesic effects of morphine on mechanical hyperalgesia and prevented the development of morphine tolerance...
August 30, 2016: Neurochemical Research
Philippe Sitbon, Alain Van Elstraete, Leila Hamdi, Victor Juarez-Perez, Jean-Xavier Mazoit, Dan Benhamou, Catherine Rougeot
BACKGROUND: Opiorphin is a naturally occurring potent analgesic human peptide. It protects enkephalins from degradation and inhibits pain perception in various acute pain models via activation of endogenous opioid pathways. However, the efficacy of opiorphin continuous infusion and its chemically stable form, STR-324, in postoperative pain is unknown. METHODS: Using the Brennan model of plantar incision-induced hypersensitivity, the authors examined the postsurgical analgesic response to mechanical and thermal stimuli of 7-day continuously intravenously infused drugs (8 to 10 rats per group)...
November 2016: Anesthesiology
Zhen Hua, LiPing Liu, Jun Shen, Katherine Cheng, Aijun Liu, Jing Yang, Lina Wang, Tingyu Qu, HongNa Yang, Yan Li, Haiyan Wu, John Narouze, Yan Yin, Jianguo Cheng
More than 240 million opioid prescriptions are dispensed annually to treat pain in the US. The use of opioids is commonly associated with opioid tolerance (OT) and opioid-induced hyperalgesia (OIH), which limit efficacy and compromise safety. The dearth of effective way to prevent or treat OT and OIH is a major medical challenge. We hypothesized that mesenchymal stem cells (MSCs) attenuate OT and OIH in rats and mice based on the understanding that MSCs possess remarkable anti-inflammatory properties and that both OT and chronic pain are associated with neuroinflammation in the spinal cord...
2016: Scientific Reports
Joanna Ripoll Rozisky, Vanessa Leal Scarabelot, Carla de Oliveira, Isabel Cristina de Macedo, Alícia Deitos, Gabriela Laste, Wolnei Caumo, Iraci L S Torres
Morphine administration in the neonatal period can induce long-term effects in pain circuitry leading to hyperalgesia induced by the opioid in adult life. This study explored a new pharmacological approach for reversing this effect of morphine. We focused on melatonin owing its well-known antinociceptive and anti-inflammatory effects, and its ability to interact with the opioid system. We used the formalin test to assess the medium and long-term effects of melatonin administration on hyperalgesia induced by morphine in early life...
October 28, 2016: Neuroscience Letters
Zhifen Wang, Yuan Yuan, Keliang Xie, Xiaohong Tang, Linlin Zhang, Jiying Ao, Nan Li, Yu Zhang, Suqian Guo, Guolin Wang
BACKGROUND: Remifentanil is used widely in clinical anesthesia because it induces more rapid and more common hyperalgesia than other opioid analgesics. Activation of N-methyl-D-aspartate (NMDA) receptors takes a pivotal part in remifentanil-induced hyperalgesia. Like NMDA receptors, the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are excitatory ion glutamate receptors in postsynaptic membrane, which are involved in the transmission of both acute and chronic pain...
September 2016: Anesthesia and Analgesia
Katsuya Kami, Fumihiro Tajima, Emiko Senba
Physical exercise, such as forced treadmill running and swimming, can sufficiently improve mechanical allodynia and heat hyperalgesia in animal models of neuropathic pain (NPP), including partial sciatic nerve ligation, chronic constriction injury, and spinal nerve ligation models. Thus, physical exercise has been established as a low-cost, safe, and effective way to manage NPP conditions, but the exact mechanisms underlying such exercise-induced hypoalgesia (EIH) are not fully understood. A growing body of evidence has identified several factors that work at different levels of the nervous system as playing important roles in producing EIH in animal models of NPP...
August 2, 2016: Anatomical Science International
Chao Zhu, Wei Li, Fan Xu, Mo Li, Liu Yang, Xue-Yu Hu, Zheng-Xu Ye, Zhe Wang, Zhuo-Jing Luo
Neuropathic pain is considered as one of the most difficult types of pain to manage with conventional analgesics. EGb-761 is extracted from leaves of Ginkgo biloba and has analgesia and anti-inflammatory properties. This study aimed to examine the effect of EGb-761 on chronic constriction injury (CCI)-induced neuropathic pain behaviors, including thermal hyperalgesia and mechanical allodynia, and to explore the possible mechanisms underlying this action. To this end, CCI mice were intraperitoneally injected with EGb-761 (10, 20, 40, and 80 mg/kg), and thermal hyperalgesia, mechanical allodynia, cytokines, and mu-opioid receptor expression were measured...
July 25, 2016: Phytotherapy Research: PTR
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