Activation of Extracellular Signal-Regulated Protein Kinase is Associated with Colorectal Distension-Induced Spinal and Supraspinal Neuronal Response and Neonatal Maternal Separation-Induced Visceral Hyperalgesia in Rats

Zhang, X. J.; Li, Z.; Chung, Elaine K.Y.; Zhang, Hong Qi; Xu, Hong‐Xi; Sung, Joseph J.Y.; Bian, Zhaoxiang

doi:10.1007/s12031-008-9134-y

Cited by 32 publications

(27 citation statements)

References 53 publications

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“…In previous studies, we found that NMS rats developed visceral hyperalgesia and enhanced neuronal sensitivity to noxious visceral stimuli in the central brain nuclei [4,5] . These nuclei, including the cingulate cortex, the thalamus and the amygdala, play important roles in the central pain matrix and are involved in generating emotional and autonomic responses [6,7] .…”

Section: Introductionmentioning

confidence: 84%

“…The increased excitability in response to visceral stimuli in the spinal cord after NMS, observed in our previous studies [4,24] , reflects changes in plasticity in descending pain circuitry. Our recent work has shown differential regulation of phospho (p)-Erk and c-Fos expression in the central pain matrix [5] . However, the mechanisms underlying these changes in plasticity are unknown.…”

Section: Introductionmentioning

confidence: 90%

“…Our recent study showed that p-Erk expression increased in the amygdala in NMS rats [5] . The present results provide evidence for the colocalization of p-Erkpositive neurons and TrkB immunoreactivity.…”

mentioning

confidence: 92%

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Neonatal Maternal Separation Increases Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B Expression in the Descending Pain Modulatory System

et al. 2009

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Neonatal maternal separation (NMS) could trigger long-term changes in the central neuronal responses to nociceptive stimuli in rats. Stress-induced visceral hyperalgesia is closely associated with the dysfunction of descending pain modulatory systems. Brain-derived neurotrophic factor (BDNF) not only has an important role in long-term synaptic plasticity but also in facilitating descending pain. The present study aimed to investigate changes in the expression of BDNF and its receptor tyrosine kinase receptor B (TrkB) in the amygdala and the rostral ventromedial medulla (RVM) after NMS and colorectal distention (CRD) stimulation in rats. Male Wistar rat pups were subjected to 180 min of daily NMS or not handled for 13 consecutive days. Expression of BDNF and TrkB following NMS and CRD stimulation was determined using immunohistochemistry. The results revealed an increase in the expression of BDNF and TrkB in the amygdala after NMS. An interactive effect of NMS and CRD on the expression of TrkB, but not BDNF, was found in the RVM. Furthermore, a significant interactive effect of NMS and CRD on the colocalization coefficient of TrkB and phospho-extracellular signal-regulated kinase expression in both the amygdala and RVM were found. These data demonstrate that NMS increases BDNF and TrkB expression in the descending pain systems, which may contribute to the development of NMS-induced visceral hyperalgesia.

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Section: Introductionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 90%

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Neonatal Maternal Separation Increases Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B Expression in the Descending Pain Modulatory System

et al. 2009

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“…Retrograde tracing studies in rat (Peschanski and Besson, 1984;Chen and Su, 1990;Otake et al, 1995;Novak et al, 2000;Krout et al, 2002) show that PVA receives projections from regions that are important in generating pain perception such as ACC, CeA, parabrachial area (PB), PAG, dorsal and medial raphe nucleus, and nucleus raphe magnus (Price, 2000;Millan, 2002). Although PVA is not commonly known as the pain matrix in the brain, increased c-Fos expression and pERK staining in PVA have been reported in several pain models in rat and mouse (Bullitt, 1990;Davies et al, 1997;Gioia et al, 2001;Chung et al, 2007;Nishii et al, 2008;Zhang et al, 2009). In the present study, pharmacological inactivation of ERK in PVA blocked the acid-induced chronic hyperalgesia in WT mice.…”

Section: Discussionmentioning

confidence: 99%

Ca_v3.2 T-Type Ca²⁺Channel-Dependent Activation of ERK in Paraventricular Thalamus Modulates Acid-Induced Chronic Muscle Pain

Chen

Liu²,

Chang³

et al. 2010

J. Neurosci.

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Treatments for chronic musculoskeletal pain, such as lower back pain, fibromyalgia, and myofascial pain syndrome, remain inadequate because of our poor understanding of the mechanisms that underlie these conditions. Although T-type Ca 2ϩ channels (T-channels) have been implicated in peripheral and central pain sensory pathways, their role in chronic musculoskeletal pain is still unclear. Here, we show that acid-induced chronic mechanical hyperalgesia develops in Ca v 3.1-deficient and wild-type but not in Ca v 3.2-deficient male and female mice. We also show that T-channels are required for the initiation, but not maintenance, of acid-induced chronic muscle pain. Blocking T-channels using ethosuximide prevented chronic mechanical hyperalgesia in wild-type mice when administered intraperitoneally or intracerebroventricularly, but not intramuscularly or intrathecally. Furthermore, we found an acid-induced, Ca v 3.2 T-channeldependent activation of ERK (extracellular signal-regulated kinase) in the anterior nucleus of paraventricular thalamus (PVA), and prevention of the ERK activation abolished the chronic mechanical hyperalgesia. Our findings suggest that Ca v 3.2 T-channel-dependent activation of ERK in PVA is required for the development of acid-induced chronic mechanical hyperalgesia.

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“…However, a similar number of c-Fos-positive neurons did not coexpress pERK1/2, indicating that alternative pathways such as protein kinase A, protein kinase C, and p38 kinase could also regulate c-Fos expression (Benavides et al, 2005;Svensson et al, 2005;Gonzá lez-Cuello et al, 2007). Regarding the association between ERK1/2 and c-Fos, some in vivo studies show that in the spinal cord, ERK1/2 is required for c-Fos expression after noxious stimulation (Cruz et al, 2007;Zhang et al, 2009), whereas others illustrate c-Fos expression in the absence of ERK1/2 activation in different animal models (Ji and Rupp, 1997;Kominato et al, 2003).…”

Section: Downloaded Frommentioning

confidence: 99%

Increased Spinal Dynorphin Levels and Phospho-Extracellular Signal-Regulated Kinases 1 and 2 and c-Fos Immunoreactivity after Surgery under Remifentanil Anesthesia in Mice

Campillo

González-Cuello²,

Cabañero³

et al. 2009

Mol Pharmacol

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In humans, remifentanil anesthesia enhances nociceptive sensitization in the postoperative period. We hypothesized that activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and the expression of c-Fos, prodynorphin (mRNA), and dynorphin in the spinal cord could participate in the molecular mechanisms underlying postoperative opioid-induced sensitization. In a mouse model of incisional pain, we evaluated thermal (Hargreaves test) and mechanical (von Frey) hyperalgesia during the first 21 postoperative days. Moreover, prodynorphin (mRNA, real-time polymerase chain reaction), dynorphin (enzymatic immunoassay), c-Fos expression, and ERK1/2 phosphorylation (both by immunohistochemistry) in the lumbar spinal cord were assessed. Surgery performed under remifentanil anesthesia induced a maximal decrease in nociceptive thresholds between 4 h and 2 days postoperatively (p Ͻ 0.001) that lasted 10 to 14 days compared with noninjured animals. In the same experimental conditions, a significant increase in prodynorphin mRNA expression (at 2 and 4 days) followed by a sustained increase of dynorphin (days 2 to 10) in the spinal cord was observed. We also identified an early expression of c-Fos immunoreactivity in the superficial laminae of the dorsal horn of the spinal cord (peak at 4 h; p Ͻ 0.001), together with a partial activation of ERK1/2 (4 h; p Ͻ 0.001). These findings suggest that activated ERK1/2 could induce c-Fos expression and trigger the transcription of prodynorphin in the spinal cord. This in turn would result in long-lasting increased levels of dynorphin that, in our model, could participate in the persistence of pain but not in the manifestation of first pain.In humans, exposure to -opioid receptor agonists during anesthesia induces delayed hyperalgesia, increasing pain and analgesic requirements in the postoperative period (Angst and Clark, 2006). The pronociceptive effects of opioids have also been reported in human volunteers and in animal models (Li et al., 2001;Angst et al., 2003). In a mouse model of postoperative pain, we have shown that postincisional pain is enhanced when the ultra-short-acting -opioid receptor agonist remifentanil is administered during anesthesia (Célé rier et al., 2006;Cabañ ero et al., 2009b). Remifentanil is commonly used in clinical practice to provide analgesia during surgery, although it has been associated with hyperalgesia in the immediate postoperative period (Angst and Clark, 2006;Joly et al., 2005).The mechanisms and signal transduction pathways that mediate pain sensitization after opioid administration are not well known. Multiple central and peripheral pathways and mechanisms have been implicated, including C-fiber sensitization, protein kinase C, the nitric oxide system, N-methyl-D-aspartate (NMDA) receptors, mitogen-activated protein kinases (MAPKs) and spinal dynorphin, among others (Angst and Clark, 2006). It has also been shown that down-regulation of ␦-opioid receptor mRNA in the dorsal root ganglia contributes to remifentanil and surgery-i...

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Activation of Extracellular Signal-Regulated Protein Kinase is Associated with Colorectal Distension-Induced Spinal and Supraspinal Neuronal Response and Neonatal Maternal Separation-Induced Visceral Hyperalgesia in Rats

Cited by 32 publications

References 53 publications

Neonatal Maternal Separation Increases Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B Expression in the Descending Pain Modulatory System

Neonatal Maternal Separation Increases Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B Expression in the Descending Pain Modulatory System

Ca_v3.2 T-Type Ca²⁺Channel-Dependent Activation of ERK in Paraventricular Thalamus Modulates Acid-Induced Chronic Muscle Pain

Increased Spinal Dynorphin Levels and Phospho-Extracellular Signal-Regulated Kinases 1 and 2 and c-Fos Immunoreactivity after Surgery under Remifentanil Anesthesia in Mice

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Activation of Extracellular Signal-Regulated Protein Kinase is Associated with Colorectal Distension-Induced Spinal and Supraspinal Neuronal Response and Neonatal Maternal Separation-Induced Visceral Hyperalgesia in Rats

Cited by 32 publications

References 53 publications

Neonatal Maternal Separation Increases Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B Expression in the Descending Pain Modulatory System

Neonatal Maternal Separation Increases Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B Expression in the Descending Pain Modulatory System

Cav3.2 T-Type Ca2+Channel-Dependent Activation of ERK in Paraventricular Thalamus Modulates Acid-Induced Chronic Muscle Pain

Increased Spinal Dynorphin Levels and Phospho-Extracellular Signal-Regulated Kinases 1 and 2 and c-Fos Immunoreactivity after Surgery under Remifentanil Anesthesia in Mice

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Ca_v3.2 T-Type Ca²⁺Channel-Dependent Activation of ERK in Paraventricular Thalamus Modulates Acid-Induced Chronic Muscle Pain