Roles of CaMKII, PKA, and PKC in the Induction and Maintenance of LTP of C-Fiber-Evoked Field Potentials in Rat Spinal Dorsal Horn

2004 ◽  
Vol 91 (3) ◽  
pp. 1122-1133 ◽  
Author(s):  
Hong-Wei Yang ◽  
Xiao-Dong Hu ◽  
Hong-Mei Zhang ◽  
Wen-Jun Xin ◽  
Ming-Tao Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Long Term Potentiation ◽  
Noxious Stimulation ◽  
Tetanic Stimulation ◽  
Field Potentials ◽  
Spinal Dorsal ◽  
Evoked Field Potentials ◽  
C Fiber

Long-term potentiation (LTP) of C-fiber-evoked field potentials in spinal dorsal horn may be relevant to hyperalgesia, an increased response to noxious stimulation. The mechanism underlying this form of synaptic plasticity is, however, still unclear. Considerable evidence has shown that calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase A (PKA), and protein kinase C (PKC) are important for LTP in hippocampus. In this study, the roles of these three protein kinases in the induction and maintenance of LTP of C-fiber-evoked field potentials were evaluated by application of specific inhibitors of CaMKII (KN-93 and AIP), PKA (Rp-CPT-cAMPS), and PKC (chelerythrine and Gö 6983) at the recording segments before and after LTP induction in urethane-anesthetized Sprague-Dawley rats. We found both KN-93 and AIP, when applied at 30 min prior to tetanic stimulation, completely blocked LTP induction. At 30 min after LTP induction, KN-93 and AIP reversed LTP completely, and at 60 min after LTP induction, they depressed spinal LTP in most rats tested. Three hours after LTP induction, however, KN-93 or AIP did not affect the spinal LTP. Rp-CPT-cAMPS, chelerythrine, and Gö 6983 blocked the spinal LTP when applied at 30 min before tetanic stimulation and reversed LTP completely at 15 min after LTP induction. In contrast, at 30 min after LTP induction, the drugs never affected the spinal LTP. These results suggest that activation of CaMKII, PKA, and PKC may be crucial for the induction and the early-phase but not for the late-phase maintenance of the spinal LTP.

Characterization of Long-Term Potentiation of C-Fiber–Evoked Potentials in Spinal Dorsal Horn of Adult Rat: Essential Role of NK1 and NK2 Receptors

1997 ◽  
Vol 78 (4) ◽  
pp. 1973-1982 ◽  
Author(s):  
X.-G. Liu ◽  
J. Sandkühler
Keyword(s):  
Dorsal Horn ◽  
High Intensity ◽  
High Frequency ◽  
Spinal Dorsal Horn ◽  
Long Term Potentiation ◽  
Field Potentials ◽  
Spinal Dorsal ◽  
C Fibers ◽  
Evoked Field Potentials ◽  
C Fiber

Liu, X.-G. and J. Sandkühler. Characterization of long-term potentiation of C-fiber–evoked potentials in spinal dorsal horn of adult rat: essential role of NK1 and NK2 receptors. J. Neurophysiol. 78: 1973–1982, 1997. Impulses in afferent C fibers, e.g., during peripheral trauma, may induce plastic changes in the spinal dorsal horn that are believed to contribute to some forms of hyperalgesia. The nature of lasting changes in spinal nociception are still not well understood. Here we characterized the long-term potentiation (LTP) of spinal field potentials with a negative focus in superficial spinal dorsal horn evoked by supramaximal electrical stimulation of the sciatic nerve in urethan-anesthetized adult rats. The field potentials studied in this work had high thresholds (≥7 V, 0.5 ms), long latencies (90–130 ms), and long chronaxy (1.1 ms) and were not abolished by muscle relaxation and spinalization. Thus they were evoked by afferent C fibers. In response to 1-Hz stimulation of afferent C fibers, amplitudes of C-fiber–evoked field potentials remained constant, whereas number of action potentials of some dorsal horn neurons increased progressively (wind-up). In all 25 rats tested, high-frequency, high-intensity stimulation (100 Hz, 30–40 V, 0.5 ms, 400 pulses given in 4 trains of 1-s duration at 10-s intervals) always induced LTP (to ∼200% of control), which consistently lasted until the end of recording periods (4–9 h). This tetanic stimulation also significantly decreased mean threshold of C-fiber–evoked field potentials. The C-fiber volley, which was recorded simultaneously in sural nerve, was, however, not affected by the same tetanic stimulation. High-frequency, low-intensity stimulation (100 Hz, 3 V, 0.5 ms) never induced LTP in six rats tested. At an intermediate frequency, high-intensity stimulation (20 Hz, 40 V, 0.5 ms, 400 pulses given in 4 trains of 5 s at 10-s intervals) induced LTP in four out of six rats, which lasted until end of recording periods (3–6 h). In the remaining two rats, no LTP was induced. Low-frequency, high-intensity stimulation (2 Hz, 30–40 V, 0.5 ms, 400 pulses) induced LTP that lasted for 2–8 h in four out of five rats. Intravenous application of neurokinin 1 (NK1) or neurokinin 2 (NK2) receptor antagonist RP 67580 (2 mg/kg, n = 5) or SR 48968 (0.3 mg/kg, n = 5) 30 min before high-frequency, high-intensity stimulation blocked the induction of LTP in all rats tested. In contrast, the same dose of their inactive enantiomers RP 68651 ( n = 5) or SR 48965 ( n = 5) did not affect the induction of LTP. Spinal superfusion with RP 67580 (1 μM) from 30 min before to 30 min after high-frequency, high-intensity stimulation blocked induction of LTP in all five rats tested. Spinal application of SR 48968 (10 nM) prevented LTP in five out of seven rats. However, when spinal superfusions with RP 67580 (1 μM, n = 3) or SR 48968 (10 nM, n = 3) were started 1 h after high-frequency, high-intensity stimulation, established LTP was not affected. Thus the activation of neurokinin receptors is necessary for the induction but not for the maintenance of LTP of C-fiber–evoked field potentials in spinal dorsal horn. This model may be useful to study plastic changes in spinal cord induced by peripheral C-fiber stimulation. The LTP of C-fiber–evoked field potentials may be a mechanism underlying some forms of hyperalgesia.

ATP induces long-term potentiation of C-fiber-evoked field potentials in spinal dorsal horn: The roles of P2X4receptors and p38 MAPK in microglia

Glia ◽  
2009 ◽  
Vol 57 (6) ◽  
pp. 583-591 ◽  
Author(s):  
Qing-Juan Gong ◽  
Yu-Ying Li ◽  
Wen-Jun Xin ◽  
Ying Zang ◽  
Wen-Jie Ren ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
P38 Mapk ◽  
Spinal Dorsal Horn ◽  
Long Term Potentiation ◽  
Field Potentials ◽  
Spinal Dorsal ◽  
Evoked Field Potentials ◽  
Term Potentiation ◽  
C Fiber

Protein Synthesis Inhibition Blocks the Late-Phase LTP of C-Fiber Evoked Field Potentials in Rat Spinal Dorsal Horn

2003 ◽  
Vol 89 (5) ◽  
pp. 2354-2359 ◽  
Author(s):  
Neng-Wei Hu ◽  
Hong-Mei Zhang ◽  
Xiao-Dong Hu ◽  
Ming-Tao Li ◽  
Tong Zhang ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Late Phase ◽  
Tetanic Stimulation ◽  
Field Potentials ◽  
Spinal Dorsal ◽  
Phase Maintenance ◽  
Evoked Field Potentials ◽  
C Fiber

Previous studies have demonstrated that in the hippocampus the maintenance of long-term potentiation (LTP) requires de novo protein synthesis. To investigate the role of protein synthesis in the maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn, which may be relevant to hyperalgesia, protein synthesis inhibitor (either cycloheximide or anisomycin) was applied locally to the recording segments of spinal cord in anesthetized rats, 30 min prior to tetanic stimulation to the sciatic nerve. We found that both cycloheximide and anisomycin selectively inhibited late-phase maintenance of the spinal LTP but affected neither LTP induction nor baseline responses of C-fiber evoked field potentials. In the presence of cycloheximide, LTP of C-fiber evoked field potentials was 281.5 ± 16.5% ( n = 6) of baseline 1 h after tetanic stimulation and the potentiation significantly decreased to 235.5 ± 18.5% at 145 min after tetanic stimulation ( P< 0.05). Afterward, LTP of C-fiber evoked field potentials decreased continuously and at 270 min after tetanic stimulation reached 130.8 ± 18.0%, which was no longer different from baseline ( P > 0.05). Spinal application of anisomycin at 30 min before tetanic stimulation yielded similar results ( n = 6). These results suggest that protein synthesis may be crucial for the late-phase maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn.

BDNF induces late-phase LTP of C-fiber evoked field potentials in rat spinal dorsal horn

2008 ◽  
Vol 212 (2) ◽  
pp. 507-514 ◽  
Author(s):  
Li-Jun Zhou ◽  
Yi Zhong ◽  
Wen-Jie Ren ◽  
Yong-Yong Li ◽  
Tong Zhang ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Late Phase ◽  
Field Potentials ◽  
Spinal Dorsal ◽  
Evoked Field Potentials ◽  
C Fiber

Activation of Spinal D1/D5 Receptors Induces Late-Phase LTP of C-Fiber–Evoked Field Potentials in Rat Spinal Dorsal Horn

2005 ◽  
Vol 94 (2) ◽  
pp. 961-967 ◽  
Author(s):  
Hong-Wei Yang ◽  
Li-Jun Zhou ◽  
Neng-Wei Hu ◽  
Wen-Jun Xin ◽  
Xian-Guo Liu
Keyword(s):  
Protein Synthesis ◽  
Dorsal Horn ◽  
Receptor Agonist ◽  
Spinal Dorsal Horn ◽  
Sch 23390 ◽  
Late Phase ◽  
Field Potentials ◽  
Spinal Dorsal ◽  
Evoked Field Potentials ◽  
C Fiber

Long-term potentiation (LTP) of C-fiber–evoked field potentials in spinal dorsal horn may be relevant to pathological pain. Our previous work has shown that the late phase of the spinal LTP is protein synthesis–dependent. Considerable evidence has accumulated that dopamine D1/D5 receptors are important for late-phase LTP in hippocampus. In this study, the role of D1/D5 receptors in LTP of C-fiber–evoked field potentials in spinal dorsal horn was evaluated in urethan-anesthetized Sprague-Dawley rats. We found the following. 1) Spinal application of SKF 38393, a D1/D5 receptor agonist, induced a slowly developed LTP of C-fiber–evoked field potentials, lasting for >10 h, and the effect was blocked by the D1/D5 antagonist SCH 23390, whereas a D2 receptor agonist (quinpirole) induced depression of C-fiber responses, lasting for 2 h. 2) The potentiation produced by D1/D5 receptor agonist occluded the late phase but not the early phase of the spinal LTP produced by tetanic stimulation. 3) SCH 23390 selectively depressed the late-phase LTP, when applied 40 min before tetanic stimulation. 4) The D1/D5 agonist-induced potentiation is blocked by the protein synthesis inhibitor anisomycin. 5) Activation of protein kinase A by spinal application of 8-Br-cAMP also induced spinal LTP, and the action occluded the potentiation induced by the D1/D5 receptor agonist. These results suggest that the spinal D1/D5 receptors participate in the protein synthesis–dependent late-phase LTP of C-fiber–evoked field potentials in spinal dorsal horn through the cAMP signaling pathway.

Diazepam inhibits the induction and maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn of rats

2006 ◽  
Vol 50 (2) ◽  
pp. 238-244 ◽  
Author(s):  
Xiao-Dong Hu ◽  
Yu-Xing Ge ◽  
Neng-Wei Hu ◽  
Hong-Mei Zhang ◽  
Li-Jun Zhou ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Field Potentials ◽  
Spinal Dorsal ◽  
Evoked Field Potentials ◽  
C Fiber

Clonidine depresses LTP of C-fiber evoked field potentials in spinal dorsal horn via NO-cGMP pathway

2006 ◽  
Vol 1118 (1) ◽  
pp. 58-65 ◽  
Author(s):  
Yu-Xing Ge ◽  
Wen-Jun Xin ◽  
Neng-Wei Hu ◽  
Tong Zhang ◽  
Ji-Tian Xu ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Field Potentials ◽  
Spinal Dorsal ◽  
Evoked Field Potentials ◽  
Cgmp Pathway ◽  
C Fiber
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