N-type voltage gated calcium channels mediate excitatory synaptic transmission in the anterior cingulate cortex of adult mice
Voltage gated calcium channels (VGCCs) are well known for its importance in synaptic transmission in the peripheral and central nervous system. However, the role of different VGCCs in the anterior cingulate cortex (ACC) has not been studied. Here, we use a multi-electrode array recording system (MED64) to study the contribution of different types of calcium channels in glutamatergic excitatory synaptic transmission in the ACC. We found that only the N-type calcium channel blocker omega-conotoxin-GVIA (omega-Ctx-GVIA) produced a great inhibition of basal synaptic transmission, especially in the superficial layer. Other calc...
Source: Molecular Pain - November 14, 2013 Category: Molecular Biology Authors: SukJae KangMing-Gang LiuTian-Yao ShiMing-Gao ZhaoBong-Kiun KaangMin Zhuo Source Type: research
Chemokine expression in peripheral tissues from the Monosodium Iodoacetate model of chronic joint pain
Conclusion:
Chemokines in general and CCL2, 7 and 9 in particular, represent promising targets for further studies into the identification of new pain mediators in chronic joint pain. (Source: Molecular Pain)
Source: Molecular Pain - November 8, 2013 Category: Molecular Biology Authors: John DawesHannes KiesewetterJames PerkinsDavid BennettStephen McMahon Source Type: research
Neurochemical characterisation of lamina II inhibitory interneurons that express GFP in the PrP-GFP mouse
Conclusions:
These findings support the view that neurochemistry provides a valuable way of classifying inhibitory interneurons in the superficial laminae. Together with previous evidence that the PrP-GFP cells form a relatively homogeneous population in terms of their physiological properties, they suggest that these neurons have specific roles in processing sensory information in the dorsal horn. (Source: Molecular Pain)
Source: Molecular Pain - October 31, 2013 Category: Molecular Biology Authors: Noboru IwagakiFrancesca GarzilloErika PolgárJohn RiddellAndrew Todd Source Type: research
Gq rather than G11 preferentially mediates nociceptor sensitization
Conclusions:
Our results demonstrate that the Gq/11 signaling branch plays a primary role in nociceptor sensitization upon stimulation with classical GPCR ligands, contributing primarily towards the development of mechanically allodynia. Moreover, the deletion of the individual G-proteins led to the finding that the Gq-protein dominates the signalling machinery of the Gq/11 family of G-proteins in nociceptive neurons. (Source: Molecular Pain)
Source: Molecular Pain - October 25, 2013 Category: Molecular Biology Authors: Laura WirotansengRohini KunerAnke Tappe-Theodor Source Type: research
The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy
Conclusions:
Oxaliplatin induced painful peripheral neuropathy in mice, an effect that was prevented by rutin and quercetin. The mechanism of action of oxaliplatin appears to be, at least, partially oxidative stress-induced damage in dorsal horn neurons, with the involvement of lipid peroxidation and protein nitrosylation. (Source: Molecular Pain)
Source: Molecular Pain - October 23, 2013 Category: Molecular Biology Authors: Maria AzevedoAnamaria PereiraRicardo NogueiraFlávio RolimGerly BritoDeysi WongRoberto Lima-JúniorRonaldo de Albuquerque RibeiroMariana Vale Source Type: research
Correlation of Nav1.8 and Nav1.9 sodium channel expression with neuropathic pain in human subjects with lingual nerve neuromas
Conclusions:
These results demonstrate that Nav1.8 and Nav1.9 are present in human lingual nerve neuromas, with significant correlations between the level of expression of Nav1.8 and symptoms of pain. These data provide further evidence that changes in expression of Nav1.8 are important in the development and/or maintenance of nerve injury-induced pain, and suggest that Nav1.8 may be a potential therapeutic target. (Source: Molecular Pain)
Source: Molecular Pain - October 21, 2013 Category: Molecular Biology Authors: Emma BirdClaire ChristmasAlison LoescherKeith SmithPeter RobinsonJoel BlackStephen WaxmanFiona Boissonade Source Type: research
Novel ¿-conotoxins from C. catus reverse signs of mouse inflammatory pain after systemic administration
Conclusions:
The present study indicates a potential for CVID and CVIE to be developed as systemically active analgesics with no accompanying neurological side-effects. (Source: Molecular Pain)
Source: Molecular Pain - October 20, 2013 Category: Molecular Biology Authors: Mahsa SadeghiSwetha MuraliRichard LewisPaul AlewoodSarasa MohammadiMacDonald Christie Source Type: research
Activation of mammalian target of rapamycin mediates rat pain-related responses induced by BmK I, a sodium channel-specific modulator
In this study, the spatiotemporal activation of mTOR that contributes to pain-related behaviors was investigated using a novel animal inflammatory pain model induced by BmK I, a sodium channel-specific modulator purified from scorpion venom. In this study, intraplantar injections of BmK I were found to induce the activation of mTOR, p70 ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) in rat L5-L6 spinal neurons. In the spinal cord, mTOR, p70 S6K and 4E-BP1 were observed to be activated in the ipsilateral and contralateral regions, peaking at 1--2 h and recovery at 24 h p...
Source: Molecular Pain - October 8, 2013 Category: Molecular Biology Authors: Feng JiangXue-Yan PangQing-Shan NiuLi-Ming HuaMing ChengYong-Hua Ji Source Type: research
Transcriptional mechanisms underlying sensitization of peripheral sensory neurons by Granulocyte-/Granulocyte-macrophage colony stimulating factors
Conclusion:
With integrative approach of bioinformatics, in vivo pharmacology and behavioral analyses, our results not only indicate that transcriptional control by G-/GMCSF signaling regulates a variety of established pain modulators, but also uncover a large number of novel targets, paving the way for translational analyses in the context of pain disorders. (Source: Molecular Pain)
Source: Molecular Pain - September 25, 2013 Category: Molecular Biology Authors: Kiran BaliVarun VenkataramaniVenkta SatagopamPooja GuptaReinhard SchneiderRohini Kuner Source Type: research
Sigma-1 receptor expression in sensory neurons and the effect of painful peripheral nerve injury
Background:
The sigma-1 receptor (sigma1R), an endoplasmic reticulum chaperone protein, is widely distributed and regulates numerous intracellular processes in neurons. Nerve injury alters the structure and function of axotomized dorsal root ganglion (DRG) neurons, contributing to the development of pain. The sigma1R is enriched in the spinal cord and modulates pain after peripheral nerve injury. However, sigma1R expression in the DRG has not been studied. We therefore characterized sigma1R expression in DRGs at baseline and following spinal nerve ligation (SNL) in rats.
Results:
Immunohistochemical (IHC) studies in DRG se...
Source: Molecular Pain - September 10, 2013 Category: Molecular Biology Authors: Madhavi BangaruDorothee WeihrauchQing-Bo TangVasiliki ZogaQuinn HoganHsiang-en Wu Source Type: research
Sex differences in opioid analgesia and addiction: interactions among opioid receptors and estrogen receptors
Opioids are widely used as the pain reliever and also notorious for being addictive drugs. Sex differences in the opioid analgesia and addiction have been reported and investigated in human subjects and animal models. Yet, the molecular mechanism underlying the differences between males and females is still unclear. Here, we reviewed the literature describing the sex differences in analgesic responses and addiction liabilities to clinically relevant opioids. The reported interactions among opioids, estrogens, opioid receptors, and estrogen receptors are also evaluated. We postulate that the sex differences partly originate...
Source: Molecular Pain - September 8, 2013 Category: Molecular Biology Authors: Cynthia Wei-Sheng LeeIng-Kang Ho Source Type: research
Roles of phosphotase 2A in nociceptive signal processing
Multiple protein kinases affect the responses of dorsal horn neurons through phosphorylation of synaptic receptors and proteins involved in intracellular signal transduction pathways, and the consequences of this modulation may be spinal central sensitization. In contrast, the phosphatases catalyze an opposing reaction of de-phosphorylation, which may also modulate the functions of crucial proteins in signaling nociception. This is an important mechanism in the regulation of intracellular signal transduction pathways in nociceptive neurons. Accumulated evidence has shown that phosphatase 2A (PP2A), a serine/threonine speci...
Source: Molecular Pain - September 8, 2013 Category: Molecular Biology Authors: Yun WangYongzhong LeiLi FangYonggao MuJing WuXuan Zhang Source Type: research
Effects of a metabotropic glutamate receptor subtype 7 negative allosteric modulator in the periaqueductal grey on pain responses and rostral ventromedial medulla cell activity in rat
The metabotropic glutamate receptor 7 (mGluR7) negative allosteric modulator, 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), was locally microinjected into the ventrolateral periaqueductal gray (VL PAG) and the effect on pain responses in formalin and spare nerve injury (SNI) -induced neuropathic pain models was monitored in the rat. The activity of rostral ventromedial medulla (RVM) "pronociceptive" ON and "antinociceptive" OFF cells was also evaluated. Intra--VL PAG MMPIP blocked the first and second phase of nocifensive behaviour in the formalin pain model. MMPIP increased the tail...
Source: Molecular Pain - September 3, 2013 Category: Molecular Biology Authors: Enza PalazzoIda MarabeseLivio LuongoSerena BoccellaGiulia BelliniMaria Elvira GiordanoFrancesca RossiMariantonietta ScafuroVito de NovellisSabatino Maione Source Type: research
S1 is associated with chronic low back pain: a functional and structural MRI study
In this study, we investigated 1) brain resting state functional connectivity (FC) differences between patients with chronic low back pain (cLBP) and matched healthy controls (HC); 2) FC differences within the cLBP patients as they experienced different levels of endogenous low back pain evoked by exercise maneuvers, and 3) morphometric differences between cLBP patients and matched HC. We found the dynamic character of FC in the primary somatosensory cortex (S1) in cLBP patients, i.e., S1 FC decreased when the patients experienced low intensity LBP as compared with matched healthy controls, and FC at S1 increased when cLBP...
Source: Molecular Pain - August 21, 2013 Category: Molecular Biology Authors: Jian KongRosa SpaethHsiao-Ying WeyAlexandra CheethamAmanda CookKarin JensenYing TanHesheng LiuDanhong WangMarco LoggiaVitaly NapadowJordan SmollerAjay WasanRandy Gollub Source Type: research
Dynamic response to peripheral nerve injury detected by in situ hybridization of IL-6 and its receptor mRNAs in the dorsal root ganglia is not strictly correlated with signs of neuropathic pain
Conclusions:
Here we evidence for the first time increased synthesis of IL-6 and IL-6R in remote cervical DRG nonassociated with the nerve injury. Our results suggest that unilateral CCI of the sciatic nerve induced not only bilateral elevation of IL-6 and IL-6R mRNAs in L4--L5 DRG but also their propagation along the neuraxis to remote cervical DRG as a general neuroinflammatory reaction of the nervous system to local nerve injury without correlation with signs of neuropathic pain. Possible functional involvement of IL-6 signaling is discussed. (Source: Molecular Pain)
Source: Molecular Pain - August 16, 2013 Category: Molecular Biology Authors: Václav BrázdaIlona KlusákováIvana Hradilová Sví¿enskáPetr Dubový Source Type: research
