Changes in expression of NMDA-NR1 receptor subunits in the rostral ventromedial medulla modulate pain behaviors

Silva, Luis Felipe S. da; Walder, Roxanne Y.; Davidson, Beverly L.; Wilson, Steven P.; Sluka, Kathleen A.

doi:10.1016/j.pain.2010.06.037

Cited by 49 publications

(63 citation statements)

References 49 publications

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“…After tissue injury, pharmacological blockade of NMDA receptors in the RVM prevents the development of hyperalgesia (Urban et al, 1999). These findings were confirmed using gene therapy to decrease the expression of the NR1 subunit in the RVM (Da Silva et al, 2010). Gene therapy has the advantage of casting light on the critical role of the NR1 subunit in the neuronal plasticity that occurs in pain-control centers during chronic pain installation (Porreca et al, 2002), allowing sustained interference upon receptor expression, which is crucial for chronic pain studies .…”

mentioning

confidence: 81%

Decrease in the expression of N‐methyl‐D‐aspartate receptors in the nucleus tractus solitarii induces antinociception and increases blood pressure

Marques-Lopes

Martins

Pinho

et al. 2011

J of Neuroscience Research

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N-methyl-D-aspartate receptors (NMDAR) have a role in cardiovascular control at the nucleus tractus solitarii (NTS), eliciting increases or decreases in blood pressure (BP), depending on the area injected with the agonists. In spite of the association between cardiovascular control and pain modulation, the effects of manipulating NMDAR in pain responses have never been evaluated. In this study, we decreased the expression of NMDAR in the NTS using gene transfer to target receptor subunits and evaluate long-term effects. Seven days after the injection of lentiviral vectors containing the NR1a subunit cDNA of NMDAR, in antisense orientation, into the intermediate NTS of Wistar rats, BP was measured, and the formalin test of nociception was performed. The antisense vector induced a decrease of NR1 expression in the NTS and elicited BP rises and hypoalgesia. Antisense vectors inhibited formalin-evoked c-Fos expression in the spinal cord, indicating decreased nociceptive activity of spinal neurons. Using a time-course approach, we verified that the onset of both the increases in BP and the hypoalgesia was at 4 days after vector injection into the NTS. The injection of NMDA into the NTS reversed the effects of antisense vectors in pain behavioral responses and spinal neuronal activation and decreased BP and heart rate. The present study shows that the NR1 subunit of the NMDAR at the NTS is critical in the regulation of tonic cardiovascular and nociceptive control and shows an involvement of the nucleus in the modulation of sustained pain.

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mentioning

confidence: 81%

Decrease in the expression of N‐methyl‐D‐aspartate receptors in the nucleus tractus solitarii induces antinociception and increases blood pressure

Marques-Lopes

Martins

Pinho

et al. 2011

J of Neuroscience Research

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“…Brain sections for each group were stained simultaneously to avoid variability between stains across days. We previously show that the staining of p-NR1 in the RVM is significantly decreased by downregulation of the NR1 subunit of the NMDA receptor with a feline immunodeficiency virus (FIV) expressing an miRNA to NR1 or increased with upregulation of the NR1 subunit of the NMDA receptor with an FIV expressing NR1 (13).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Phosphorylation of NR1 would be expected to enhance neuron excitability by increasing the number of NMDA receptors transported to the cell membrane and increasing glutamate-induced currents through NMDA receptors (9,17,49,65). The NMDA receptor in the RVM is critical for the development of hyperalgesia after muscle insult, with our prior studies showing blockade of NMDA receptors reduces hyperalgesia, increasing NR1 enhances nociception, and decreasing NR1 prevents chronic muscle hyperalgesia (13,53). We propose that the normal state of the nervous system is associated with regular physical activity and that physical inactivity is the "disease state" setting up the nervous system to respond in an exaggerated way to a muscle insult and develop chronic pain (see schematic diagram Fig.…”

Section: Mechanisms Of Exercise-induced Analgesiamentioning

confidence: 99%

“…In addition to mediating analgesia, the RVM also facilitates pain behaviors after tissue insult, including chronic muscle pain (44,53,55). The N-methyl-D-aspartate (NMDA) glutamate receptor in the RVM is critical for the development of hypersensitivity after muscle insult: increasing the NR1 subunit of the NMDA receptor enhances nociception, decreasing NR1 prevents chronic muscle pain (13), and blocking the NMDA receptor reverses pain sensitivity (13,53). Further, there is increased phosphorylation of NR1 (p-NR1) in animal models of chronic muscle pain (13); these experiments were done in sedentary animals.…”

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confidence: 99%

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Regular physical activity prevents development of chronic pain and activation of central neurons

Sluka

O’Donnell

Danielson

et al. 2013

Journal of Applied Physiology

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167

168

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“…59 NMDA receptors within the rostral ventromedial medulla are important in modulating pain. 60 Miranda et al 61 reported that spinal NMDA receptors play an important role in the development of hyperalgesia following painful events early in life.…”

Section: 55mentioning

confidence: 99%

Role of Principal Ionotropic and Metabotropic Receptors in Visceral Pain

Kannampalli

Sengupta

2015

J Neurogastroenterol Motil

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Visceral pain is the most common form of pain caused by varied diseases and a major reason for patients to seek medical consultation. It also leads to a significant economic burden due to workdays lost and reduced productivity. Further, long-term use of non-specific medications is also associated with side effects affecting the quality of life. Despite years of extensive research and the availability of several therapeutic options, management of patients with chronic visceral pain is often inadequate, resulting in frustration for both patients and physicians. This is, most likely, because the mechanisms associated with chronic visceral pain are different from those of acute pain. Accumulating evidence from years of research implicates several receptors and ion channels in the induction and maintenance of central and peripheral sensitization during chronic pain states. Understanding the specific role of these receptors will facilitate to capitalize on their unique properties to augment the therapeutic efficacy while at the same time minimizing unwanted side effects. The aim of this review is to provide a concise review of the recent literature that reports on the role of principal ionotropic receptors and metabotropic receptors in the modulation visceral pain. We also include an overview of the possibility of these receptors as potential new targets for the treatment of chronic visceral pain conditions. (J Neurogastroenterol Motil 2015;21:147-158)

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Changes in expression of NMDA-NR1 receptor subunits in the rostral ventromedial medulla modulate pain behaviors

Abstract: SummaryIncreasing the NR1 subunit of the NMDA receptor in the RVM produces hyperalgesia, while decreasing NR1 in the RVM produces hypoalgesia and prevents development of chronic muscle hyperalgesia.

Cited by 49 publications

References 49 publications

Decrease in the expression of N‐methyl‐D‐aspartate receptors in the nucleus tractus solitarii induces antinociception and increases blood pressure

Decrease in the expression of N‐methyl‐D‐aspartate receptors in the nucleus tractus solitarii induces antinociception and increases blood pressure

Regular physical activity prevents development of chronic pain and activation of central neurons

Role of Principal Ionotropic and Metabotropic Receptors in Visceral Pain

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