Changes in Properties of Spinal Dorsal Horn Neurons and Their Sensitivity to Morphine after Spinal Cord Injury in the Rat

2005 ◽  
Vol 102 (1) ◽  
pp. 152-164 ◽  
Author(s):  
Jungang Wang ◽  
Mikito Kawamata ◽  
Akiyoshi Namiki

Background To gain a better understanding of spinal cord injury (SCI)-induced central neuropathic pain, the authors investigated changes in properties of spinal dorsal horn neurons located rostrally and caudally to the lesion and their sensitivity to morphine in rats after SCI. Methods The right spinal cord of Sprague-Dawley rats was hemisected at the level of L2. At 10 to 14 days after the SCI, when mechanical hyperalgesia/allodynia had fully developed, spontaneous activity and evoked responses to mechanical stimuli of wide-dynamic-range (WDR) and high-threshold neurons rostral and caudal to the lesion were recorded. Effects of cumulative doses of systemic (0.1-3 mg/kg) and spinal (0.1-5 microg) administration of morphine on spontaneous activity and evoked responses to the stimuli of the neurons were evaluated. Results Spontaneous activity significantly increased in WDR neurons both rostral and caudal to the SCI site, but high-frequency background discharges with burst patterns were only observed in neurons rostral to the SCI site. Significant increases in responses to the mechanical stimuli were seen both in WDR and high-threshold neurons located both rostrally and caudally to the lesion. The responses to nonnoxious and noxious stimuli were significantly greater in caudal WDR neurons than in rostral WDR neurons. In contrast, the responses to pinch stimuli were significantly higher in rostral high-threshold neurons than those in caudal high-threshold neurons. Systemically administered morphine had a greater effect on responses to nonnoxious and noxious stimuli of rostral WDR neurons than those of caudal WDR neurons. Spinally administered morphine significantly suppressed responses of WDR neurons in SCI animals to nonnoxious stimuli compared with those in sham-operated control animals. Conclusions The findings suggest that changes in properties of spinal dorsal horn neurons after SCI are caused by different mechanisms, depending on the classification of the neurons and their segmental locations.




1990 ◽  
Vol 63 (2) ◽  
pp. 273-285 ◽  
Author(s):  
P. D. Ryu ◽  
M. Randic

1. Calcium currents in immature rat spinal dorsal horn neurons in transverse slices were studied with the single-electrode voltage-clamp technique. Using experimental conditions that minimized voltage-dependent Na+ and K+ currents, we distinguished low- and high-voltage-activated calcium currents on the basis of their voltage dependence and sensitivity to the Ca2(+)-channel agonist and antagonist drugs. 2. The low-voltage-activated transient calcium current is evoked with weak depolarizing voltage commands. It begins to activate at potentials positive to -70 mV and increases in amplitude and rate of decay with depolarization, the peak values being reached between -40 and -30 mV. The current is fully activated at a holding potential of about -110 mV. Steady-state inactivation is complete at potentials in the range of -60 to -50 mV. 3. The transient component of the high-threshold calcium current appears at membrane potentials close to -40 mV and slowly decays within several hundreds of milliseconds. The amplitude of the current increases with more negative holding potentials (-100 to -40 mV). 4. The sustained component of the high-threshold calcium current seems to activate at potentials positive to -40 mV and exhibits little inactivation during 0.3- to 0.5-s depolarizing commands. This component is better isolated at more depolarized holding potentials (between -40 and -30 mV) that inactivate the transient components of the low- and high-threshold calcium currents. 5. A rundown of calcium currents was seen in dorsal horn cells. The time stability of the transient and sustained components of the high-threshold calcium current was lower than that of the low-threshold transient current. The latter current seemed to be insensitive up to 1 h. 6. (-)-Bay K 8644 (1-10 microM), a dihydropyridine agonist, enhanced the high-threshold calcium current, in particular the sustained component, but not the transient low-threshold calcium current. The dihydropyridine antagonist nifedipine (5-50 microM) selectively reduced the sustained component of the high-threshold calcium current while having little or no effect on the transient components of the low- and high-threshold calcium currents. 7. Cadmium ions (60-100 microM) and cobalt ions (2 mM) markedly reduced both components of the high-threshold calcium current, and Cd2+ only slightly decreased the low-threshold transient current. However, all three components are indiscriminately blocked by higher concentrations of Cd2+ and Co2+.(ABSTRACT TRUNCATED AT 400 WORDS)



2002 ◽  
Vol 87 (2) ◽  
pp. 732-739 ◽  
Author(s):  
Guo-Du Wang ◽  
Min Zhuo

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-d-aspartate (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.



1999 ◽  
Vol 88 (4) ◽  
pp. 893-897 ◽  
Author(s):  
Yoshiya Miyazaki ◽  
Takehiko Adachi ◽  
Jun Utsumi ◽  
Tsutomu Shichino ◽  
Hajime Segawa


1999 ◽  
Vol 88 (4) ◽  
pp. 893-897 ◽  
Author(s):  
Yoshiya Miyazaki ◽  
Takehiko Adachi ◽  
Jun Utsumi ◽  
Tsutomu Shichino ◽  
Hajime Segawa


2009 ◽  
Vol 65 ◽  
pp. S142
Author(s):  
Daisuke Sugiyama ◽  
Hidemasa Furue ◽  
Keiji Imoto ◽  
Mikito Kawamata


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