Cyclic adenosine 3′5′-monophosphate potentiates excitatory amino acid and synaptic responses of rat spinal dorsal horn neurons

Cerne, R.; Jiang, Michael; Randić, Mirjana

doi:10.1016/0006-8993(92)91538-p

Cited by 52 publications

(20 citation statements)

References 70 publications

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“…These findings are agreement with the observation that phosphorylation of NMDA receptors occurs in other types of neurons, such as hippocampal neurons, and that the phosphorylation may lead to an enhancement in responses to NMDA (Wang et al, 1996;Christie et al, 1999). In vitro studies of spinal cord dorsal horn neurons are consistent with this idea Huang, 1991, 1992;Cerne et al, 1992Cerne et al, , 1993Rusin et al, 1993).…”

Section: Discussionsupporting

confidence: 80%

“…Central sensitization of STT cells depends on the activation of several protein kinases (PKs), including PKC, PKG, and PKA (Lin et al, 1996(Lin et al, , 1997aSluka et al, 1997). Similarly, PKC and PKA have been shown to produce a long-lasting enhancement of excitatory responses of dorsal horn neurons in in vitro preparations Huang, 1991, 1992;Cerne et al, 1992Cerne et al, , 1993Rusin et al, 1993). The responses of neurons in slices of the trigeminal nucleus caudalis to NMDA are enhanced after injection of PKC into the neurons (Chen and Huang, 1991), and these enhanced responses can be explained by an increased probability of channel openings and a reduction in the voltage-dependent Mg 2ϩ block of the NMDA receptor channels (Chen and Huang, 1992).…”

mentioning

confidence: 99%

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Enhanced Phosphorylation of NMDA Receptor 1 Subunits in Spinal Cord Dorsal Horn and Spinothalamic Tract Neurons after Intradermal Injection of Capsaicin in Rats

2000

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The functional enhancement of NMDA receptors after peripheral tissue injury is proposed to contribute to the sensitization of spinothalamic tract (STT) cells and hyperalgesia. Protein phosphorylation is a major mechanism for the regulation of NMDA receptor function. In this study, Western blots, immunofluorescence double labeling, and the retrograde tracing method were used to examine whether phosphorylation of NMDA receptor 1 (NR1) subunits increases in spinal cord tissue and spinal dorsal horn neurons, especially in STT cells, after injection of capsaicin (CAP) into the glabrous skin of one hindpaw of anesthetized rats. Western blots showed that phosphorylated NR1 protein in spinal cord tissue was increased 30 min after CAP injection. Immunofluorescence double-labeling staining showed no significant difference in the number of the NR1-like immunoreactive neurons in laminae I-VII in the lumbosacral segments (L 4 -S 1 ) on the ipsilateral and the contralateral sides 30 min after CAP or vehicle injection. However, the numbers of phospho-NR1-like immunoreactive neurons were significantly increased on the ipsilateral side compared with the vehicle injection group. STT cells were labeled by bilateral microinjections of the retrograde tracer fluorogold into the lateral thalamus, including the ventral-posterior lateral nucleus. Immunofluorescence staining was performed at 30, 60, and 120 min after CAP injection or at 30 min after vehicle injection. There was a significant increase in the proportion of STT cells with phosphorylated NR1 subunits compared either with the contralateral side 30 and 60 min after CAP injection or either side of animals after intradermal injection of vehicle. These results provide direct evidence that NMDA receptors in STT cells are phosphorylated after CAP injection. Key words: NMDA receptor subunit; phosphorylation; STT cell; retrograde tracing; dorsal horn; nociceptionSpinothalamic tract (STT) cells transmit nociceptive information from the spinal cord to the thalamus (Willis, 1985;Gybels and Sweet 1989;Willis and Coggeshall, 1991). Extracellular glutamate and aspartate concentrations increase significantly in the spinal cord dorsal horn after peripheral inflammation (Sluka and Westlund, 1992, 1993a;Sorkin et al., 1992;Sorkin and McAdoo, 1993;Sluka and Willis, 1998), and this increase is believed to underlie hyperalgesia and allodynia (Sluka and Westlund, 1993b) by enhancing the excitability of nociceptive dorsal horn neurons, including STT cells (Aanonsen et al., 1990; Willis, 1991, 1992; Dougherty et al., 1992a,b). Intrathecal administration of glutamate agonists such as NMDA elicits nociceptive behavior (Aanonsen and Wilcox, 1987), and spinal cord administration of an NMDA receptor antagonist attenuates hyperalgesia and allodynia (Haley et al., 1990; Ren et al., 1992a,b;Ren and Dubner, 1993;Sluka et al., 1994). At a cellular level, central sensitization of STT cells can be initiated by iontophoretic co-release of NMDA and substance P (cf. Randic et al., 1990;Dougherty and Willis, 1991...

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Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

Enhanced Phosphorylation of NMDA Receptor 1 Subunits in Spinal Cord Dorsal Horn and Spinothalamic Tract Neurons after Intradermal Injection of Capsaicin in Rats

2000

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“…Activation of several receptors for sensory transmitters such as glutamate and CGRP has been reported to raise cAMP levels. In slices or isolated cells from young animals, cAMP analogue enhanced glutamate receptor-mediated synaptic responses (Cerne et al 1992(Cerne et al , 1993 or no effect on AMPA/kainate receptor-mediated synaptic responses (Hori et al 1996). In the present studies, application of forskolin did not significantly affect synaptic responses induced by dorsal root stimulation in slices of adult mice.…”

Section: Synergistic Effect Between Camp and Serotonincontrasting

confidence: 53%

Synergistic Enhancement of Glutamate-Mediated Responses by Serotonin and Forskolin in Adult Mouse Spinal Dorsal Horn Neurons

Wang

Zhuo

2002

Journal of Neurophysiology

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Wang, Guo-Du and Min Zhuo. Synergistic enhancement of glutamate-mediated responses by serotonin and forskolin in adult mouse spinal dorsal horn neurons. J Neurophysiol 87: 732-739, 2002; 10.1152/jn.00423.2001. Glutamate is the major excitatory amino acid neurotransmitter in the CNS, including the neocortex, hippocampus, and spinal cord. Normal synaptic transmission is mainly mediated by glutamate AMPA and/or kainate receptors. Glutamate N-methyl-Daspartate (NMDA) receptors are normally inactive and only activated when a sufficient postsynaptic depolarization is induced by the activity. Here we show that in sensory synapses of adult mouse, some synaptic responses (26.3% of a total of 38 experiments) between primary afferent fibers and dorsal horn neurons are almost completely mediated by NMDA receptors. Dorsal root stimulation did not elicit any detectable AMPA/kainate receptor-mediated responses in these synapses. Unlike young spinal cord, serotonin alone did not produce any long-lasting synaptic enhancement in adult spinal dorsal horn neurons. However, co-application of the adenylyl cyclase activator forskolin and serotonin (5-HT) produced long-lasting enhancement, including the recruitment of functional AMPA receptor-mediated responses. Calcium-sensitive, calmodulin-regulated adenylyl cyclases (AC1, AC8) are required for the enhancement. Furthermore the thresholds for generating action potential responses were decreased, and, in many cases, co-application of forskolin and 5-HT led to the generation of action potentials by previously subthreshold stimulation of primary afferent fibers in the presence of the NMDA receptor blocker 2-amino-5-phosphonovaleric acid. Our results suggest that pure NMDA synapses exist on sensory neurons in adult spinal cord and that they may contribute to functional sensory transmission. The synergistic recruitment of functional AMPA responses by 5-HT and forskolin provides a new cellular mechanism for glutamatergic synapses in mammalian spinal cord.

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“…Activation of several receptors for sensory transmitters such as glutamate and calcitonin gene related peptide (CGRP) has been reported to raise cAMP levels. In slices or isolated cells from young animals, a cAMP analog enhanced glutamate receptor mediated synaptic responses (Cerne et al, 1992;1993) or had no effect on AMPA/kainate receptor mediated synaptic responses (Hori et al, 1996). In a recent study, application of forskolin did not significantly affect synaptic responses induced by dorsal root stimulation in slices of adult mice.…”

Section: Coactivation Of Calcium-stimulated Adenylyl Cyclases In Adulmentioning

confidence: 97%

Endogenous Facilitation: From Molecular Mechanisms to Persistent Pain

Robinson

Calejesan²,

Feng³

et al. 2004

CNR

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It is well documented that sensory transmission, including pain, is subject to endogenous inhibitory modulatory influences at dorsal horn of the spinal cord. Recent results, from behavioral to molecular studies, demonstrate that endogenous modulatory systems are bi-phasic, including inhibitory as well as new facilitatory systems. In this review, we propose the existence of endogenous facilitatory systems in the brain, and review evidence supporting the hypothesis. We believe that understanding molecular and cellular mechanisms of endogenous facilitatory systems hold the hope for better future treatment of patients with chronic pain.

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Cyclic adenosine 3′5′-monophosphate potentiates excitatory amino acid and synaptic responses of rat spinal dorsal horn neurons

Cited by 52 publications

References 70 publications

Enhanced Phosphorylation of NMDA Receptor 1 Subunits in Spinal Cord Dorsal Horn and Spinothalamic Tract Neurons after Intradermal Injection of Capsaicin in Rats

Enhanced Phosphorylation of NMDA Receptor 1 Subunits in Spinal Cord Dorsal Horn and Spinothalamic Tract Neurons after Intradermal Injection of Capsaicin in Rats

Synergistic Enhancement of Glutamate-Mediated Responses by Serotonin and Forskolin in Adult Mouse Spinal Dorsal Horn Neurons

Endogenous Facilitation: From Molecular Mechanisms to Persistent Pain

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