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Adult-Age Inflammatory Pain Experience Enhances Long-Term Pain Vigilance in Rats  [PDF]
Sheng-Guang Li, Jin-Yan Wang, Fei Luo
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036767
Abstract: Background Previous animal studies have illustrated a modulatory effect of neonatal pain experience on subsequent pain-related behaviors. However, the relationship between chronic pain status in adulthood and future pain perception remains unclear. Methodology/Principal Findings In the current study, we investigated the effects of inflammatory pain experience on subsequent formalin-evoked pain behaviors and fear conditioning induced by noxious stimulation in adult rats. Our results demonstrated an increase of the second but not the first phase of formalin-induced pain behaviors in animals with a history of inflammatory pain that have recovered. Similarly, rats with persistent pain experience displayed facilitated acquisition and prolonged retention of pain-related conditioning. These effects of prior pain experience on subsequent behavior were prevented by repeated morphine administration at an early stage of inflammatory pain. Conclusions/Significance These results suggest that chronic pain diseases, if not properly and promptly treated, may have a long-lasting impact on processing and perception of environmental threats. This may increase the susceptibility of patients to subsequent pain-related disorders, even when chronic pain develops in adulthood. These data highlight the importance of treatment of chronic pain at an early stage.
Abdominal Pain in Adult Sickle Cell Disease Patients: A Nigerian Experience
TS Akingbola, B Kolude, EC Aneni, AA Raji, KU Iwara, YA Aken’Ova, OA Soyannwo
Annals of Ibadan Postgraduate Medicine , 2011,
Abstract: Background: Abdominal pain is a relatively frequent occurrence in sickle cell disease. The aetiology of abdominal pain in sickle cell disease is often difficult to diagnose clinically. Despite the frequent occurrence, diagnostic dilemma, and the need for an accurate, early diagnosis, abdominal pain in sickle cell disease has not been rigorously studied. Objective: We therefore sought to describe the different presentations and patterns of abdominal pain in persons with sickle cell disease. Methods: A prospective case series of 20 patients was done in which data was collected on demographic characteristics, hemoglobin electrophoresis patterns, a description of the abdominal pain including sites, severity, and type of pain, packed cell volume and the provisional and final diagnosis. Results: Haemoglobin S patients were 17 in number constituting eightyfive percent (85%) of our study population whilst the rest 3 were Hb S+C. Most patients (70%) had one site of abdominal pain. The pain was mainly colicky or tightening, moderate to severe in nature and, in some cases, associated with vomiting. We did not find any significant difference between the steady state PCV and the PCV during the acute abdominal pain episodes. The final diagnosis showed that only 38.8% of the patients had vasoocclusive crises and the reliability index between the provisional diagnosis and the final diagnosis was 67%. Conclusion: Abdominal pain in sickle cell disease may present in different ways and it is important to recognize that the possible diagnoses are numerous. Not all cases are due to vasoocclusive crises. Early diagnosis and prompt treatment can be life saving.
Dropout of adult learners returning to university: interactions of motivational and environmental factors  [PDF]
Jacot, A.,Frenay, M.,Cazan, A.-M.
Bulletin of the Transilvania University of Bra?ov. Series VII : Social Sciences and Law , 2010,
Abstract: The purpose of this paper is to highlight how motivational and contextual factors interact together to explain the dropout process of adult learners returning to university. From seventeen semi-structured interviews, four main interactions have been identified between entry motives, dimensions of perceived value and expectancy, life and learning contexts. The findings from this study indicated that studying dropout of adult learners with motivational factors enables a deeper understanding taking into account the different commitments of this population and the motivational dynamic.
Correlates of Some Motivational Factors on the Performance of Adult French Learners in Nigeria
Oluranti Ogunbiyi
Pakistan Journal of Social Sciences , 2012,
Abstract: This study sought to determine the degree of prediction of some motivational factors on the performance of adult French learners. Specifically, the influence of the following motivational factors were examined: Perception of needs, job placement and attitude to French language. An ex-post-facto research design was used in the study. Three hundred and fifty-four first year adult learners from 9 adult French learning centers in Oyo, Ogun and Lagos States were selected purposively for the study. Data was collected using 3 instruments, a French language Attitudinal Scale (FLAS), a Questionnaire on Motivation for French Learning (QMFL) and a French Language Performance Test (FLPT). Essentially, the data were subjected to multiple regression analysis. From the results, it was discovered that the selected motivational variables viz; perception of needs, job placement and attitude to French language, actually have a high predictive value for adult learners achievement in French language. Learners attitudes to French language stand out as the most significant variable in predicting performance of adult French learners. Implications of these findings for motivating adults to learn are discussed in the study.
Activation of Erk in the anterior cingulate cortex during the induction and expression of chronic pain
Feng Wei, Min Zhuo
Molecular Pain , 2008, DOI: 10.1186/1744-8069-4-28
Abstract: Recent studies have consistently indicated that Erk signaling cascade plays an important role in activity-dependent plasticity in the central nervous system (CNS) and may contribute to the molecular mechanisms underlying learning, memory and persistent pain. Previous studies have found that tissue and nerve injury transiently activates Erk pathway in the spinal dorsal horn neurons, and the activation of Erk is required for the central sensitization during the development of hyperalgesia and allodynia [1-5]. In supraspinal structures, it has been reported that activation of Erk in the amygdala is induced by peripheral injury [6], and the increased Erk activity in this region is acquired for behavioral sensitization to mechanical stimulation after injury [7]. The ACC has been found to be an important site for cortical regulation of nociception and persistent pain after amputation [8-11]. Long-term potentiation (LTP) in ACC neurons is the likely synaptic model for persistent pain [12-16]. Recent studies using pharmacological inhibitors has showed that the activity of Erk contributes to synaptic potentiation caused by LTP induction protocols [17], and that such inhibitors are relatively selective and do not affect basic synaptic transmission. However, little is known about the possible involvement of Erk in the ACC after tissue or nerve injury in adult animals.To determine the possible activation of Erk in the ACC during acute or chronic pain after peripheral injury, we carried out experiments in adult male rats using two different injury models. Activation of Erk was monitored by immunostaining with an antibody that detects the activated form of Erk (phosphorylated on both thr-202 and Try-204, P-Erk). For the first pain model, 5% formalin was injected into the dorsal part of the unilateral hindpaw as previously reported [18]. At three different time points between 15 min to 90 min after the formalin injection, rats were killed by rapidly anesthetized and perfused throu
Guanylate cyclase-C/cGMP: an emerging pathway in the regulation of visceral pain  [PDF]
Gerhard Hannig,Boris Tchernychev
Frontiers in Molecular Neuroscience , 2014, DOI: 10.3389/fnmol.2014.00031
Abstract: Activation of guanylate cyclase-C (GC-C) expressed predominantly on intestinal epithelial cells by guanylin, uroguanylin or the closely related GC-C agonist peptide, linaclotide, stimulates generation, and release of cyclic guanosine-3′,5′-monophosphate (cGMP). Evidence that the visceral analgesic effects of linaclotide are mediated by a novel, GC-C-dependent peripheral sensory mechanism was first demonstrated in animal models of visceral pain. Subsequent studies with uroguanylin or linaclotide have confirmed the activation of a GC-C/cGMP pathway leading to increased submucosal cGMP mediated by cGMP efflux pumps, which modulates intestinal nociceptor function resulting in peripheral analgesia. These effects can be reproduced by the addition of exogenous cGMP and support a role for GC-C/cGMP signaling in the regulation of visceral sensation, a physiological function that has not previously been linked to the GC-C/cGMP pathway. Notably, targeting the GC-C/cGMP pathway for treatment of gastrointestinal pain and abdominal sensory symptoms has now been validated in the clinic. In 2012, linaclotide was approved in the United States and European Union for the treatment of adult patients with irritable bowel syndrome with constipation.
A Trigeminoreticular Pathway: Implications in Pain  [PDF]
W. Michael Panneton, Qi Gan, Robert S. Livergood
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024499
Abstract: Neurons in the caudalmost ventrolateral medulla (cmVLM) respond to noxious stimulation. We previously have shown most efferent projections from this locus project to areas implicated either in the processing or modulation of pain. Here we show the cmVLM of the rat receives projections from superficial laminae of the medullary dorsal horn (MDH) and has neurons activated with capsaicin injections into the temporalis muscle. Injections of either biotinylated dextran amine (BDA) into the MDH or fluorogold (FG)/fluorescent microbeads into the cmVLM showed projections from lamina I and II of the MDH to the cmVLM. Morphometric analysis showed the retrogradely-labeled neurons were small (area 88.7 μm2±3.4) and mostly fusiform in shape. Injections (20–50 μl) of 0.5% capsaicin into the temporalis muscle and subsequent immunohistochemistry for c-Fos showed nuclei labeled in the dorsomedial trigeminocervical complex (TCC), the cmVLM, the lateral medulla, and the internal lateral subnucleus of the parabrachial complex (PBil). Additional labeling with c-Fos was seen in the subnucleus interpolaris of the spinal trigeminal nucleus, the rostral ventrolateral medulla, the superior salivatory nucleus, the rostral ventromedial medulla, and the A1, A5, A7 and subcoeruleus catecholamine areas. Injections of FG into the PBil produced robust label in the lateral medulla and cmVLM while injections of BDA into the lateral medulla showed projections to the PBil. Immunohistochemical experiments to antibodies against substance P, the substance P receptor (NK1), calcitonin gene regulating peptide, leucine enkephalin, VRL1 (TPRV2) receptors and neuropeptide Y showed that these peptides/receptors densely stained the cmVLM. We suggest the MDH- cmVLM projection is important for pain from head and neck areas. We offer a potential new pathway for regulating deep pain via the neurons of the TCC, the cmVLM, the lateral medulla, and the PBil and propose these areas compose a trigeminoreticular pathway, possibly the trigeminal homologue of the spinoreticulothalamic pathway.
The spinal notch signaling pathway plays a pivotal role in the development of neuropathic pain
Yan-Yan Sun, Li Li, Xiao-Hua Liu, Nan Gu, Hai-Long Dong, Lize Xiong
Molecular Brain , 2012, DOI: 10.1186/1756-6606-5-23
Abstract: We found that the Notch intracellular domain (NICD) is expressed in the DRG (Dorsal Root Ganglia), sciatic nerve and spinal cord in normal rats, and is upregulated in the sciatic nerve and spinal cord after spared nerve injury (SNI). Moreover, we used the γ-secretase (a key enzyme of the Notch signaling pathway) inhibitor DAPT to observe the effect of the Notch signaling pathway after SNI. We found that intrathecal DAPT significantly increased paw withdrawal thermal latency and mechanical threshold. Mechanical hyperalgesia occurring after SNI could be significantly reversed by DAPT in a dose-dependent manner.These results suggest that the Notch signaling pathway participates in the induction and maintenance of neuropathic pain, which indicates that the Notch pathway maybe a potential drug target for neuropathic pain treatment.
Downregulation of selective microRNAs in trigeminal ganglion neurons following inflammatory muscle pain
Guang Bai, Rajini Ambalavanar, Dong Wei, Dean Dessem
Molecular Pain , 2007, DOI: 10.1186/1744-8069-3-15
Abstract: Inflammation associated with some pathologies may develop allodynia or hyperalgesia defined as an over-reaction to non-noxious or noxious stimuli, respectively [1,2]. Gene expression is an important molecular mechanism underlying inflammatory pain since the measured steady-state levels of mRNA and/or protein in pain/nociceptive pathway in animal models are actively altered during the development and maintenance of pain [2-6]. Our understanding of how individual genes are selectively regulated during inflammatory pain is limited mostly to the regulation of transcriptional control [2]. MicroRNA (miRNA) represents a group of small noncoding RNAs in 18~23 nucleotide sequences. These evolutionarily conserved molecules mainly interfere with gene expression at posttranscriptional levels and moderately promote RNA degradation by acting on specific sequences in the 3' untranslated region of target mRNA, while some of them inhibit gene transcription by participating in chromatin remodeling [7-9]. While many miRNAs have been detected in the nervous system [10-12], their functional significance has been restricted mostly to events involving nervous system development [10,13-18]. Although miRNAs are present in mature neurons, their functionality and regulation remain largely unexplored.To explore the mechanism(s) underlying the gene alteration during inflammatory pain and to investigate the function of miRNA in the adult nervous system, we quantified several neuronal miRNAs in a model of inflammatory muscle pain. We injected CFA (150 μl, oil:saline = 1:1, Sigma, St. Louis, MO) unilaterally into the masseter muscle of male rats (Sprague-Dawley, ~250 gr, Harlan, Indianapolis, IN). This injection produced significant mechanical allodynia while intramuscular injection of saline did not [4,6]. After the development of allodynia, we dissected the ophthalmic and maxillary divisions (V1/2) and V3 from individual TGs. Tissues were combined from two animals and cellular RNA was extracted
Differential proteomics analysis of the analgesic effect of electroacupuncture intervention in the hippocampus following neuropathic pain in rats  [cached]
Gao Yong-Hui,Chen Shu-Ping,Wang Jun-Ying,Qiao Li-Na
BMC Complementary and Alternative Medicine , 2012, DOI: 10.1186/1472-6882-12-241
Abstract: Background Evidence is building steadily on the effectiveness of acupuncture therapy in pain relief and repeated acupuncture-induced pain relief is accompanied by improvement of hippocampal neural synaptic plasticity. To further test the cellular and molecular changes underlying analgesic effect of acupuncture, the global change of acupuncture associated protein profiles in the hippocampus under neuropathic pain condition was profiled. Methods The chronic constrictive injury (CCI) model was established by ligature of the unilateral sciatic nerve in adult Wistar rats. Rats were randomized into normal control (NC) group, CCI group, and CCI with electroacupuncture (EA) stimulation group. EA was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) in the EA group. Differentially expressed proteins in the hippocampus in the three groups were identified by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. The functional clustering of the identified proteins was analyzed by Mascot software. Results After CCI, the thermal pain threshold of the affected hind footpad was decreased and was reversed gradually by 12 sessions of acupuncture treatment. Following EA, there were 19 hippocampal proteins identified with significant changes in expression (>2-fold), which are involved in metabolic, physiological, and cellular processes. The top three canonical pathways identified were “cysteine metabolism”, “valine, leucine, and isoleucine degradation” and “mitogen-activated protein kinase (MAPK) signaling”. Conclusions These data suggest that the analgesic effect of EA is mediated by regulation of hippocampal proteins related to amino acid metabolism and activation of the MAPK signaling pathway.
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