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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
Xiao-Qian Li, Zai-Li Zhang, Wen-Fei Tan, Xi-Jia Sun, Hong Ma
Toll-like receptor 4 (TLR4) is important for the pathogenesis of inflammatory reactions and the promotion of pain processing after ischemia/reperfusion (IR) in spinal cord. Recently, C-X-C chemokine ligand 12 (CXCL12) and its receptor, C-X-C chemokine receptor 4 (CXCR4), were demonstrated to be simultaneously critical for inflammatory reactions, thereby facilitating glial activation. However, whether CXCL12/CXCR4 expression can contribute to IR-induced inflammatory pain via spinal TLR4 remained unclear. A rat model was established by 8 min of aortic arch occlusion...
2016: PloS One
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
Lovish Marwaha, Yashika Bansal, Raghunath Singh, Priyanka Saroj, Rupinder Kaur Sodhi, Anurag Kuhad
TRP channels have been discovered as a specialized group of somatosensory neurons involved in the detection of noxious stimuli. Desensitization of TRPV1 located on dorsal root and trigeminal ganglia exhibits analgesic effect and makes it potential therapeutic target for treatment of neuropathic pain. With this background, the present study was aimed to investigate the protective effect of niflumic acid, a TRPV1 modulator, on stavudine (STV)-induced neuropathic pain in rats. Stavudine (50 mg/kg) was administered intravenously via tail vein in rats to induce neuropathic pain...
October 18, 2016: Inflammopharmacology
Yeon Sun Lee, Michael Remesic, Cyf Ramos-Colon, Sara M Hall, Alexander Kuzmin, David Rankin, Frank Porreca, Josephine Lai, Victor J Hruby
Nerve injury and inflammation cause up-regulation of an endogenous opioid ligand, dynorphin A (Dyn A), in the spinal cord resulting in hyperalgesia via the interaction with bradykinin receptors (BRs). This is a non-opioid neuroexcitatory effect that cannot be blocked by opioid antagonists. Our systematic structure-activity relationships study on Dyn A identified lead ligands 1 and 4, along with the key structural feature (i.e. amphipathicity) for the BRs. However, the ligands showed very low metabolic stability in plasma (t1/2 <1h) and therefore, in order to improve their metabolic stabilities with retained biological activities, various modifications were performed...
October 6, 2016: Bioorganic & Medicinal Chemistry Letters
Petra Mrozkova, Diana Spicarova, Jiri Palecek
Protease-activated receptors 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) receptors in the peripheral nerve endings are implicated in the development of increased sensitivity to mechanical and thermal stimuli, especially during inflammatory states. Both PAR2 and TRPV1 receptors are co-expressed in nociceptive dorsal root ganglion (DRG) neurons on their peripheral endings and also on presynaptic endings in the spinal cord dorsal horn. However, the modulation of nociceptive synaptic transmission in the superficial dorsal horn after activation of PAR2 and their functional coupling with TRPV1 is not clear...
2016: PloS One
Meagan E Ita, Nathan D Crosby, Ben A Bulka, Beth A Winkelstein
STUDY DESIGN: Immunohistochemistry labeled pre- and post-synaptic structural markers to quantify excitatory and inhibitory synapses in the spinal superficial dorsal horn at 14 days after painful facet joint injury in the rat. OBJECTIVE: The objective of this study was to investigate the relationship between pain and synapse density in the spinal cord after facet injury. SUMMARY OF BACKGROUND DATA: Neck pain is a major contributor to disability and often becomes chronic...
October 17, 2016: Spine
Julie M Waldfogel, Suzanne Nesbit, Steven P Cohen, Sydney M Dy
Opioids remain the mainstay of treatment for severe cancer pain, but up to 20% of patients have persistent or refractory pain despite rapid and aggressive opioid titration, or develop refractory pain after long-term opioid use. In these scenarios, alternative agents and mechanisms for analgesia should be considered. This case report describes a 28-year-old man with metastatic pancreatic neuroendocrine cancer with severe, intractable pain despite high-dose opioids including methadone and a hydromorphone patient-controlled analgesia (PCA)...
October 18, 2016: Journal of Pain & Palliative Care Pharmacotherapy
Nikele Nadur-Andrade, Camila Squarzoni Dale, Victoria Regina da Silva Oliveira, Elaine Flamia Toniolo, Regiane Dos Santos Feliciano, José Antonio da Silva, Stella Regina Zamuner
BACKGROUND: Envenoming induced by Bothrops snakebites is characterized by drastic local tissue damage that involves an intense inflammatory reaction and local hyperalgesia which are not neutralized by conventional antivenom treatment. Herein, the effectiveness of photobiomodulation to reduce inflammatory hyperalgesia induced by Bothrops moojeni venom (Bmv), as well as the mechanisms involved was investigated. METHODOLOGY/PRINCIPAL FINDINGS: Bmv (1 μg) was injected through the intraplantar route in the right hind paw of mice...
October 2016: PLoS Neglected Tropical Diseases
Cheng-Hua Zhou, Ming-Xing Zhang, Sha-Sha Zhou, Huan Li, Jian Gao, Lei Du, Xiao-Xing Yin
Accumulating evidence has demonstrated that epigenetic modification-mediated changes in pain-related gene expressions play an important role in the development and maintenance of neuropathic pain. Sirtuin 1 (SIRT1), anicotinamide adenosine dinucleotide (NAD)-dependent deacetylase, is involved in the development of chronic pain. Moreover, SIRT1 may be a novel therapeutic target for the prevention of type 2 diabetes mellitus (T2DM). But the role of SIRT1 in T2DM-induced neuropathic pain remains unknown. In this study, we found that spinal SIRT1 expression and activity were down-regulated significantly in high-fat-fed/low-dose STZ-induced neuropathic pain rats...
September 29, 2016: Pain
Ajit Kumar, Sanjeev K Bhoi, Jayantee Kalita, Usha K Misra
OBJECTIVE: In view of the paucity of studies on central poststroke pain (CPSP), in this hospital-based prospective study, we evaluated the frequency, the spectrum, imaging, and quantitative sensory testing in a cohort of stroke patients with CPSP. METHODS: Stroke patients who developed CPSP at onset or during follow-up were included. Patients were subjected to clinical evaluation and sensory testing. The severity of stroke was defined by the Modified Rankin Scale and disability by the Barthel Index...
November 2016: Clinical Journal of Pain
Lijuan Lu, Cailong Pan, Lu Chen, Liang Hu, Chaoyu Wang, Yuan Han, Zhixiang Cheng, Yanjing Yang, Wen-Tao Liu
Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. Ozone is widely used as an alternative therapy for many different pain conditions, with exact mechanisms still elusive. In this study, we found that a single peri-sciatic nerve injection of ozone decreased mechanical allodynia and thermal hyperalgesia, and normalized the phosphorylation of protein kinase C γ (PKCγ), N-methyl-D-aspartate receptor (NMDAR), and extracellular signal-regulated kinase in a chronic constriction injury (CCI) model in rat sciatic nerve...
October 15, 2016: Journal of Molecular Cell Biology
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
Min Kyoung Kim, Myung Sub Yi, Hyun Kang, Geun-Joo Choi
Remifentanil and nitrous oxide (N2O) are 2 commonly used anesthetic agents. Both these agents are known risk factors for postoperative nausea and vomiting (PONV). However, remifentanil and N2O have not been directly compared in a published study. Remifentanil can induce acute tolerance or hyperalgesia, thus affecting postoperative pain. The objective of this retrospective study is to compare the effects of remifentanil and N2O on PONV and pain in patients receiving intravenous patient-controlled analgesia (IV-PCA) after thyroidectomy...
October 2016: Medicine (Baltimore)
Suzie Noten, Filip Struyf, Enrique Lluch, Marika D'Hoore, Eveline Van Looveren, Mira Meeus
BACKGROUND: Shoulder pain is a common health problem in which changes in shoulder structure cannot always explain the patient's perceived pain. Central sensitization (CS) might play a role in a subgroup of these patients. METHODS: The literature was systematically reviewed to address the role of CS in patients with shoulder pain. Electronic databases PubMed and Web of Knowledge were searched for relevant studies. RESULTS: Eighteen full-text articles were included, methodological quality was scored, and information was extracted...
October 14, 2016: Pain Practice: the Official Journal of World Institute of Pain
Pooria Sarrami, Elizabeth Armstrong, Justine M Naylor, Ian A Harris
BACKGROUND: Whiplash injuries are among the leading injuries related to car crashes and it is important to determine the prognostic factors that predict the outcome of patients with these injuries. This meta-review aims to identify factors that are associated with outcome after acute whiplash injury. MATERIALS AND METHODS: A systematic search for all systematic reviews on outcome prediction of acute whiplash injury was conducted across several electronic databases...
October 13, 2016: Journal of Orthopaedics and Traumatology: Official Journal of the Italian Society of Orthopaedics and Traumatology
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
Fabíula Francisca Abreu, Ana Carla Araujó de Souza, Simone Aparecida Teixeira, Antônio Garcia Soares, Daiane Franco Teixeira, Rosilene Calazans Soares, Marilia Trindade Santana, Sandra Lauton Santos, Soraia Kátia Pereira Costa, Marcelo Nicolas Muscará, Enilton Aparecido Camargo
INTRODUCTION: Acute pancreatitis (AP) may be severe and cause hospitalization or death, and the available treatment is insufficient to control pancreatic inflammation and pain. Rutin is a natural flavonoid with the potential to treat AP via anti-inflammatory, antinociceptive and antioxidant activities. AIM: This study investigated the beneficial effects of rutin on experimental AP induced by L-arginine administration in mice. METHODS: The L-arginine-induced AP model was used in Swiss mice (n = 6-8)...
October 13, 2016: Free Radical Research
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