Gene expression profiling of melanocortin system in neuropathic rats supports a role in nociception

Beltramo, Massimiliano; Campanella, Marilena; Tarozzo, Glauco; Fredduzzi, Silva; Corradini, Laura; Forlani, Angelo; Bertorelli, Rosalia; Reggiani, Angelo

doi:10.1016/j.molbrainres.2003.08.001

Cited by 34 publications

(17 citation statements)

References 29 publications

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“…In this study, β-actin was used as the reference gene to normalize expression levels. The relative gene expression level was computed from the target and β-actin using the following formula [3,24,27]: mRNA relative expression = 2 − (Ct of target − Ct of β-actin) . Primers were designed with Invitrogen Custom Primer Designer.…”

Section: Methodsmentioning

confidence: 99%

Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain

Zhang

Guo

Peng

et al. 2009

Pain

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Using the chronic constriction injury (CCI) model of neuropathic pain, we profiled gene expression in the rat spinal cord, and identified SIP30 as a gene whose expression was elevated after CCI. SIP30 was previously shown to interact with SNAP25, but whose function was otherwise unknown. We now show that in the spinal cord, SIP30 was present in dorsal horn laminae where peripheral nociceptive inputs first synapse, colocalizing with nociception-related neuropeptides CGRP and substance P. With the onset of neuropathic pain after CCI surgery, SIP30 mRNA and protein levels increased in the ipsilateral side of the spinal cord, suggesting a potential association between SIP30 and neuropathic pain. When CCI-upregulated SIP30 was inhibited by intrathecal antisense oligonucleotide administration, neuropathic pain was attenuated. This neuropathic pain-reducing effect was observed both during neuropathic pain onset following CCI, and after neuropathic pain was fully established, implicating SIP30 involvement in the development and maintenance phases of neuropathic pain. Using a secretion assay in PC12 cells, anti-SIP30 siRNA decreased the total pool of synaptic vesicles available for exocytosis, pointing to a potential function for SIP30. These results suggest a role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain.

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Section: Methodsmentioning

confidence: 99%

Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain

Zhang

Guo

Peng

et al. 2009

Pain

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“…Expression of POMC, β -END, ACTH, α -MSH, the endogenous antagonist Agouti-Related Protein (AgRP), and MC4R has been detected in areas of the spinal cord involved in nociception, underscoring the role of this system in nociceptive transmission [82–85]. Concordantly, several studies have shown that antagonism of the melanocortin system reduces neuropathic pain [86–88] and prevents morphine withdrawal hyperalgesia [89].…”

Section: Pomc-derived Peptidesmentioning

confidence: 99%

Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases

Carniglia

Ramírez

Durand

et al. 2017

Mediators of Inflammation

174

122

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Microglial cells are responsible for immune surveillance within the CNS. They respond to noxious stimuli by releasing inflammatory mediators and mounting an effective inflammatory response. This is followed by release of anti-inflammatory mediators and resolution of the inflammatory response. Alterations to this delicate process may lead to tissue damage, neuroinflammation, and neurodegeneration. Chronic pain, such as inflammatory or neuropathic pain, is accompanied by neuroimmune activation, and the role of glial cells in the initiation and maintenance of chronic pain has been the subject of increasing research over the last two decades. Neuropeptides are small amino acidic molecules with the ability to regulate neuronal activity and thereby affect various functions such as thermoregulation, reproductive behavior, food and water intake, and circadian rhythms. Neuropeptides can also affect inflammatory responses and pain sensitivity by modulating the activity of glial cells. The last decade has witnessed growing interest in the study of microglial activation and its modulation by neuropeptides in the hope of developing new therapeutics for treating neurodegenerative diseases and chronic pain. This review summarizes the current literature on the way in which several neuropeptides modulate microglial activity and response to tissue damage and how this modulation may affect pain sensitivity.

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“…It has been shown that bone metabolism is related to energy metabolism and regulated substantially by the central nervous system [2], [3], [4], [5]. Agouti-related protein (AgRP) neurons co-expressing neuropeptide Y (NPY) are localized specifically in the medial section of hypothalamic arcuate nucleus (ARC) and play an essential role in promoting food consumption and suppressing energy expenditure [6], [7], [8], [9], [10], [11]. Recently, it was shown that the neural activity of AgRP neurons plays a role in bone metabolism [12].…”

Section: Introductionmentioning

confidence: 99%

PDK1-FoxO1 pathway in AgRP neurons of arcuate nucleus promotes bone formation via GHRH-GH-IGF1 axis

Sasanuma¹,

Nakata

Parmila

et al. 2017

Molecular Metabolism

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ObjectiveIn the hypothalamic arcuate nucleus (ARC), orexigenic agouti-related peptide (AgRP) neurons regulate feeding behavior and energy homeostasis, functions connected to bone metabolism. The 3-phosphoinositide-dependent protein kinase-1 (PDK1) serves as a major signaling molecule particularly for leptin and insulin in AgRP neurons. We asked whether PDK1 in AGRP neurons also contributes to bone metabolism.MethodsWe generated AgRP neuron-specific PDK1 knockout (Agrp Pdk1−/−) mice and those with additional AgRP neuron-specific expression of transactivation-defective FoxO1 (Agrp Pdk1−/−Δ256Foxo1). Bone metabolism in KO and WT mice was analyzed by quantitative computed tomography (QCT), bone histomorphometry, measurement of plasma biomarkers, and qPCR analysis of peptides.ResultsIn Agrp Pdk1−/− female mice aged 6 weeks, compared with Agrp Cre mice, both stature and femur length were shorter while body weight was unchanged. Cortical bone mineral density (BMD) and cancellous BMD in the femur decreased, and bone formation was delayed. Furthermore, plasma GH and IGF-1 levels were reduced in parallel with decreased mRNA expressions for GH in pituitary and GHRH in ARC. Osteoblast activity was suppressed and osteoclast activity was enhanced. These changes in stature, BMD and GH level were rescued in Agrp Pdk1−/−Δ256Foxo1 mice, suggesting that the bone abnormalities and impaired GH release were mediated by enhanced Foxo1 due to deletion of PDK1.ConclusionsThis study reveals a novel role of PDK1-Foxo1 pathway of AgRP neurons in controlling bone metabolism primarily via GHRH-GH-IGF-1 axis.

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Gene expression profiling of melanocortin system in neuropathic rats supports a role in nociception

Cited by 34 publications

References 29 publications

Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain

Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain

Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases

PDK1-FoxO1 pathway in AgRP neurons of arcuate nucleus promotes bone formation via GHRH-GH-IGF1 axis

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