Differential expression of microRNAs in mouse pain models

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are short non-coding RNAs that inhibit translation of target genes by binding to their mRNAs. The expression of numerous brain-specific miRNAs with a high degree of temporal and spatial specificity suggests that miRNAs play an important role in gene regulation in health and disease. Here we investigate the time course gene expression profile of miR-1, -16, and -206 in mouse dorsal root ganglion (DRG), and spinal cord dorsal horn under inflammatory and neuropathic pain conditions as well as following acute noxious stimulation.</p> <p>Results</p> <p>Quantitative real-time polymerase chain reaction analyses showed that the mature form of miR-1, -16 and -206, is expressed in DRG and the dorsal horn of the spinal cord. Moreover, CFA-induced inflammation significantly reduced miRs-1 and -16 expression in DRG whereas miR-206 was downregulated in a time dependent manner. Conversely, in the spinal dorsal horn all three miRNAs monitored were upregulated. After sciatic nerve partial ligation, miR-1 and -206 were downregulated in DRG with no change in the spinal dorsal horn. On the other hand, axotomy increases the relative expression of miR-1, -16, and 206 in a time-dependent fashion while in the dorsal horn there was a significant downregulation of miR-1. Acute noxious stimulation with capsaicin also increased the expression of miR-1 and -16 in DRG cells but, on the other hand, in the spinal dorsal horn only a high dose of capsaicin was able to downregulate miR-206 expression.</p> <p>Conclusions</p> <p>Our results indicate that miRNAs may participate in the regulatory mechanisms of genes associated with the pathophysiology of chronic pain as well as the nociceptive processing following acute noxious stimulation. We found substantial evidence that miRNAs are differentially regulated in DRG and the dorsal horn of the spinal cord under different pain states. Therefore, miRNA expression in the nociceptive system shows not only temporal and spatial specificity but is also stimulus-dependent.</p

Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

Summary: Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, regardless of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble DkTx. Together, our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization. : Oxytocin is known to suppress painful stimuli of inflammatory origin. Nersesyan et al. now find that oxytocin attenuates pain via the pain-sensing receptor TRPV1. Keywords: transient receptor potential vanilloid 1, TRPV1 ion channel, oxytocin, nociception, oxytocin receptor, planar lipid bilayers, molecular dynamics simulations, MD simulation

Reação do tecido conjuntivo subcutâneo de ratos ao implante de Artglass®: estudo histológico

Indirect composite resin systems have been routinely recommended for making restorations in distressed patients. The purpose of this study was to evaluate histologically in rats the effect of chronic stress on the reaction of subcutaneous connective tissue after implant of Artglass™. For this purpose, 60 rats were divided into four groups (GI (control), GII (stressed), GIII (Artglass™) and GIV (Artglass™. / stressed) received dorsal subcutaneous implants of polyethylene tubes containing saline solution (GI and GII) or Artglass™ (GIII and GIV). In groups of four animals were sacrificed at 7,14 and 28 days postoperatively. The results allowed to observe more intense inflammatory reaction and tissue organization later in the animals subjected to stress.Sistemas indiretos de resina composta têm sido rotineiramente indicados para confecção de restaurações em pacientes estressados. O propósito deste trabalho foi estudar histologicamente em ratos o efeito do estresse crônico sobre a reação do tecido conjuntivo subcutâneo ao implante de Artglass®. Para tanto, 60 ratos, divididos em quatro grupos (GI (controle), GII (estressado), GIII (Artglass®) e GIV (Artglass®/Estressado) receberam implante subcutâneo, bilateral e dorsal, de tubos de polietileno contendo soro fisiológico (Grupos I e II) ou Artglass® (Grupos III e IV). Em grupos de cinco, os animais foram sacrificados aos 7,14 e 28 dias pós-operatórios. Os resultados obtidos permitiram observar reação inflamatória mais intensa e organização do tecido conjuntivo mais tardia nos animais submetidos ao estresse

Efeito do envelhecimento e do estresse crônico sobre a reação do tecido conjuntivo subcutâneo: estudo histológico em ratos

Physiological functions undergo a gradual retardation that begins around 25-30 years and extends to the death. Moreover, this change affects most severely the activities more complex and more intricate responses to tensions or stress. The purpose of this study was to evaluate histologically in aged rats the effect of chronic stress on the reaction of subcutaneous connective tissue. The purpose of this study was to evaluate histologically in aged rats the effect of chronic stress on the reaction of subcutaneous connective tissue. For this purpose, 60 rats were divided into four groups (GI (control), GII (stressed), GIII (elderly) and GIV (aged / stressed) received dorsal subcutaneous implants of polyethylene tubes containing saline solution. In groups of four animals were sacrificed at 7,14 and 28 days postoperatively. The results allowed to observe more intense inflammatory reaction and tissue organization later in the aged animals subjected to stress.As funções fisiológicas sofrem um retardo gradual que se inicia por volta de 25-30 anos e se estende até a morte. Além disso, esta alteração afeta mais gravemente as atividades mais complexas e as respostas mais intrincadas às tensões ou estresse. O propósito deste trabalho foi estudar histologicamente em ratos idosos o efeito do estresse crônico sobre a reação do tecido conjuntivo subcutâneo. Para tanto, 60 ratos, divididos em quatro grupos (GI (controle), GII (estressado), GIII (idoso) e GIV (Idoso/Estressado) receberam implante subcutâneo, bilateral e dorsal, de tubos de polietileno contendo soro fisiológico. Em grupos de cinco, os animais foram sacrificados aos 7,14 e 28 dias pós-operatórios. Os resultados obtidos permitiram observar reação inflamatória mais intensa e organização do tecido conjuntivo mais tardia nos animais idosos submetidos ao estresse

Odontoblast TRPC5 channels signal cold pain in teeth.

peer reviewedTeeth are composed of many tissues, covered by an inflexible and obdurate enamel. Unlike most other tissues, teeth become extremely cold sensitive when inflamed. The mechanisms of this cold sensation are not understood. Here, we clarify the molecular and cellular components of the dental cold sensing system and show that sensory transduction of cold stimuli in teeth requires odontoblasts. TRPC5 is a cold sensor in healthy teeth and, with TRPA1, is sufficient for cold sensing. The odontoblast appears as the direct site of TRPC5 cold transduction and provides a mechanism for prolonged cold sensing via TRPC5's relative sensitivity to intracellular calcium and lack of desensitization. Our data provide concrete functional evidence that equipping odontoblasts with the cold-sensor TRPC5 expands traditional odontoblast functions and renders it a previously unknown integral cellular component of the dental cold sensing system