ß-arrestin-2-biased agonism of delta opioid receptors sensitizes transient receptor potential vanilloid type 1 (TRPV1) in primary sensory neurons
Despite advances in understanding the signaling mechanisms involved in the development and maintenance of chronic pain, the pharmacologic treatment of chronic pain has seen little advancement. Agonists at the mu opioid receptor (MOPr) continue to be vital in the treatment of many forms of chronic pain, but side-effects limit their clinical utility and range from relatively mild, such as constipation, to major, such as addiction and dependence. Additionally, chronic activation of MOPr results in pain hypersensitivity known as opioid-induced hyperalgesia (OIH), and we have shown recently that recruitment of beta-arrestin2 to...
Source: Molecular Pain - August 1, 2014 Category: Molecular Biology Authors: Matthew RowanKalina SzteynAllison DoyleRuben GomezMichael HenryNathaniel Jeske Source Type: research
beta-arrestin-2-biased agonism of delta opioid receptors sensitizes transient receptor potential vanilloid type 1 (TRPV1) in primary sensory neurons
Despite advances in understanding the signaling mechanisms involved in the development and maintenance of chronic pain, the pharmacologic treatment of chronic pain has seen little advancement. Agonists at the mu opioid receptor (MOPr) continue to be vital in the treatment of many forms of chronic pain, but side-effects limit their clinical utility and range from relatively mild, such as constipation, to major, such as addiction and dependence. Additionally, chronic activation of MOPr results in pain hypersensitivity known as opioid-induced hyperalgesia (OIH), and we have shown recently that recruitment of beta-arrestin2 to...
Source: Molecular Pain - August 1, 2014 Category: Molecular Biology Authors: Matthew RowanKalina SzteynAllison DoyleRuben GomezMichael HenryNathaniel Jeske Source Type: research
IL-10 mediated by herpes simplex virus vector reduces neuropathic pain induced by HIV gp120 combined with ddC in rats
Conclusion:
The blocking of the signaling of these proinflammatory molecules is able to reduce HIV-related neuropathic pain, which provide a novel mechanism-based approach to treating HIV-associated neuropathic pain using gene therapy (Source: Molecular Pain)
Source: Molecular Pain - July 30, 2014 Category: Molecular Biology Authors: Wenwen ZhengWan HuangShue LiuRoy LevittKeith CandiottiDavid LubarskyShuanglin Hao Source Type: research
Exploring pharmacological activities and signaling of morphinans substituted in position 6 as potent agonists interacting with the mu opioid receptor
Conclusion:
Development of such novel chemotypes by targeting position 6 provides valuable insights on ligand-receptor interaction and molecular mode of action, and may aid in identification of opioid therapeutics with enhanced analgesic properties and fewer undesirable effects. (Source: Molecular Pain)
Source: Molecular Pain - July 24, 2014 Category: Molecular Biology Authors: Tanila Ben HaddouDavide MalfaciniGirolamo CaloMario AcetoLouis HarrisJohn TraynorAndrew CoopHelmut SchmidhammerMariana Spetea Source Type: research
Expression profiling of genes modulated by minocycline in a rat model of neuropathic pain
Conclusion:
In this work, we confirmed gene expression alterations previously identified by microarray analysis in the spinal cord and analyzed the expression of selected genes in the DRG. Moreover, we reviewed the literature to illustrate the relevance of these findings for neuropathic pain development and therapy. Further studies are needed to elucidate the roles of the individual genes in neuropathic pain and to determine the therapeutic role of minocycline in the rat neuropathic pain model. (Source: Molecular Pain)
Source: Molecular Pain - July 19, 2014 Category: Molecular Biology Authors: Ewelina RojewskaMichal Korosty¿skiRyszard PrzewlockiBarbara PrzewlockaJoanna Mika Source Type: research
Higher serum S100B and BDNF levels are correlated with a lower pressure-pain threshold in fibromyalgia
Conclusions:
Both neuroglia key mediators in the CS process were inversely correlated with the PPT. Serum assessment of BDNF and S100B deserve further study to determine its potential as a proxy for the CS spectrum in FM. (Source: Molecular Pain)
Source: Molecular Pain - July 8, 2014 Category: Molecular Biology Authors: Simone ZanetteJairo Dussan-SarriaAndressa SouzaAlicia DeitosIraci TorresWolnei Caumo Source Type: research
Local translation and retrograde axonal transport of CREB regulates IL-6-induced nociceptive plasticity
Transcriptional regulation of genes by cyclic AMP response element binding protein (CREB) is essential for the maintenance of long-term memory. Moreover, retrograde axonal trafficking of CREB in response to nerve growth factor (NGF) is critical for the survival of developing primary sensory neurons. We have previously demonstrated that hindpaw injection of interleukin-6 (IL-6) induces mechanical hypersensitivity and hyperalgesic priming that is prevented by the local injection of protein synthesis inhibitors. However, proteins that are locally synthesized that might lead to this effect have not been identified. We hypothes...
Source: Molecular Pain - July 4, 2014 Category: Molecular Biology Authors: Ohannes MelemedjianDipti TilluJamie MoyMarina AsieduEdward MandellSourav GhoshGregory DussorTheodore Price Source Type: research
Contribution of TRPC3 to store-operated calcium entry and inflammatory transductions in primary nociceptors
Conclusions:
Our findings highlight a major contribution of TRPC3 to neuronal calcium homeostasis in somatosensory pathways based on the unique ability of these cation channels to engage in both SOCE and receptor-operated calcium influx. This is the first evidence for TRPC3 as a SOCE component in DRG neurons. The flexible role of TRPC3 in calcium signaling as well as its functional coupling to pro-inflammatory metabotropic receptors involved in peripheral sensitization makes it a potential target for therapeutic strategies in chronic pain conditions. (Source: Molecular Pain)
Source: Molecular Pain - June 26, 2014 Category: Molecular Biology Authors: Hazim AlkhaniAriel AseRebecca GrantDajan O¿DonnellKlaus GroschnerPhilippe Séguéla Source Type: research
Descending controls modulate inflammatory joint pain and regulate CXC chemokine and iNOS expression in the dorsal horn
Conclusions:
These findings demonstrate that joint pain behaviour is dependent in part on descending facilitation via the RVM, and identify a novel pathway driving CXC chemokine and iNOS expression in the dorsal horn. (Source: Molecular Pain)
Source: Molecular Pain - June 20, 2014 Category: Molecular Biology Authors: Fiona CarrSandrine GérantonStephen Hunt Source Type: research
Decreased pain threshold and enhanced synaptic transmission in the anterior cingulate cortex of experimental hypothyroidism mice
Conclusions:
These results suggest that HT promotes hypersensitivity to noxious thermal, and that supplementation with T3 or T4 rescues the imbalance between excitatory and inhibitory transmission in the ACC. (Source: Molecular Pain)
Source: Molecular Pain - June 18, 2014 Category: Molecular Biology Authors: Jun YiJian-yong ZhengWei ZhangShan WangZhi-fu YangKe-feng Dou Source Type: research
Gain and loss of function of P2X7 receptors: mechanisms, pharmacology and relevance to diabetic neuropathic pain
Conclusions:
Our present results confirm the physiological relevance of some of the SNPs in the P2RX7 gene and show that the presence of these genetic variants correlates with pain sensitivity also in a diabetic neuropathic pain patient population. (Source: Molecular Pain)
Source: Molecular Pain - June 16, 2014 Category: Molecular Biology Authors: Daniel UrsuPhilip EbertEmily LangronCara RubleLeanne MunsieWei ZouBonnie FijalYue-Wei QianTerry McNearneyAdrian MoggOlivera GrubishaKalpana MerchantEmanuele Sher Source Type: research
Peripheral administration of morphine attenuates postincisional pain by regulating macrophage polarization through COX-2-dependent pathway
Conclusions:
Local administration of morphine alleviated the development of postincisional pain, possibly by altering macrophage polarity at the incisional sites. A morphine-induced shift in macrophage phenotype may be mediated by a COX-2-dependent mechanism. Therefore, mu-opioid receptor signaling in macrophages may be a potential therapeutic target during the early phase of postincisional pain development. (Source: Molecular Pain)
Source: Molecular Pain - June 14, 2014 Category: Molecular Biology Authors: Kohei GodaiMaiko Hasegawa-MoriyamaTae KurimotoTakayuki SaitoTomotsugu YamadaTakahiro SatoMasayasu KojimaYuichi Kanmura Source Type: research
Spinal 5-HT3 receptors mediate descending facilitation and contribute to behavioral hypersensitivity via a reciprocal neuron-glial signaling cascade
Conclusions:
These findings offer new insights into the cellular and molecular mechanisms at the spinal level responsible for descending 5-HT-mediated pain facilitation during the development of persistent pain after tissue and nerve injury. New pain therapies should focus on prime targets of descending facilitation-induced glial involvement, and in particular the blocking of intercellular signaling transduction between neurons and glia. (Source: Molecular Pain)
Source: Molecular Pain - June 9, 2014 Category: Molecular Biology Authors: Wei GuoKan MiyoshiRonald DubnerMing GuMan LiJian LiuJiale YangShiping ZouKe RenKoichi NoguchiFeng Wei Source Type: research
Age-dependent sensitization of cutaneous nociceptors during developmental inflammation
Conclusion:
These data suggest that the mechanisms of neonatal pain development may be generated by different afferent subtypes and receptors/channels in an age-related manner. (Source: Molecular Pain)
Source: Molecular Pain - June 7, 2014 Category: Molecular Biology Authors: Michael JankowskiJessica RossJonathon WeberFrank LeeAaron ShankRenita Hudgins Source Type: research
Postsynaptic potentiation of corticospinal projecting neurons in the anterior cingulate cortex after nerve injury
Long-term potentiation (LTP) is the key cellular mechanism for physiological learning and pathological chronic pain. In the anterior cingulate cortex (ACC), postsynaptic recruitment or modification of AMPA receptor (AMPAR) GluA1 contribute to the expression of LTP. Here we report that pyramidal cells in the deep layers of the ACC send direct descending projecting terminals to the dorsal horn of the spinal cord (lamina I-III). After peripheral nerve injury, these projection cells are activated, and postsynaptic excitatory responses of these descending projecting neurons were significantly enhanced. Newly recruited AMPARs co...
Source: Molecular Pain - June 3, 2014 Category: Molecular Biology Authors: Tao ChenKohei KogaGiannina DescalziShuang QiuJian WangLe-Shi ZhangZhi-Jian ZhangXiao-Bin HeXin QinFu-Qiang XuJi HuFeng WeiRichard HuganirYun-Qing LiMin Zhuo Source Type: research
