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Biomedical subjects

Z Q Zhao

Publications and source records attributed to Z Q Zhao.

At least 19 recordsLinked to original sources
PubMed2006

Thermal nociception in adult Drosophila: behavioral characterization and the role of the painless gene.

Nociception, warning of injury that should be avoided, serves an important protective function in animals. In this study, we show that adult Drosophila avoids noxious heat by a jump response. To quantitatively analyze this nociceptive behavior, we developed two assays. In the CO2 laser beam assay, flies exhibit this behavior when a laser beam heats their abdomens. The consistency of the jump latency in this assay meets an important criterion for a good nociceptive assay. In the hot plate assay, flies jump quickly to escape from a hot copper plate (>45 degrees C). Our results demonstrate that, as in mammals, the latency of the jump response is inversely related to stimulus intensity, and innoxious thermosensation does not elicit this nociceptive behavior. To explore the genetic mechanisms of nociception, we examined several mutants in both assays. Abnormal nociceptive behavior of a mutant, painless, indicates that painless, a gene essential for nociception in Drosophila larvae, is also required for thermal nociception in adult flies. painless is expressed in certain neurons of the peripheral nervous system and thoracic ganglia, as well as in the definite brain structures, the mushroom bodies. However, chemical or genetic insults to the mushroom bodies do not influence the nociceptive behavior, suggesting that different painless-expressing neurons play diverse roles in thermal nociception. Additionally, no-bridge(KS49), a mutant that has a structural defect in the protocerebral bridge, shows defective response to noxious heat. Thus, our results validate adult Drosophila as a useful model to study the genetic mechanisms of thermal nociception.

Animals↗
PubMed2002

Activated polymorphonuclear leukocytes induce cardiomyocyte apoptosis and the protective effects of carvedilol.

Previous studies have shown that ischemia and reperfusion are potent stimuli for eliciting cardiomyocyte apoptosis, and that polymorphonuclear leukocytes (PMNs) are involved in the development of myocardial injury induced by ischemia and reperfusion. The present study examined whether PMN could directly induce cardiomyocyte apoptosis and, if so, it possible signal transduction pathways. In addition, we also investigated the effects of carvedilol, a potent antioxidant, on PMN-induced apoptosis. Cultured primary neonatal rat cardiomyocytes were exposed to PAF-activated PMNs at concentrations of 10(5), 3 x 10(5) and 10(6) cells/well for 48 h. Multiple detecting techniques, including electron microscopy, DNA gel electrophoresis. TUNEL assay and flow cytometry were used to identify myocyte apoptosis. All of these techniques demonstrated that activated PMNs directly induced cardiomyocyte apoptosis in a concentration-dependent manner, while unactivated PMNs showed no such effect. Activated PMN-induced apoptosis was partially inhibited by SB203580, a specific inhibitor of the p38-MAPK signaling system. Carvedilol (at a dose range of 1-10 mumol/l) significantly prevented activated PMN-induced cardiomyocyte apoptosis. These results suggest that PMNs, when activated, directly induce cardiomyocyte apoptosis and that the p38-MAPK signaling pathway might be involved in this process. Carvedilol may prevent PMN-induced apoptosis possibly because of its antioxidant properties.

Animals↗
PubMed2001

Change in excitability and phenotype of substance P and its receptor in cat Abeta sensory neurons following peripheral inflammation.

The effect of peripheral inflammation on spontaneous firing and level of substance P (SP) and its receptor in electrophysiologically identified cat Abeta neurons of dorsal root ganglion (DRG) was studied in vivo using a combination of intracellular recording, dye injection and immunohistochemical techniques. Following injection of carrageenan (Carg) into cat hindpaw, the number of Abeta neurons with spontaneous firing was enhanced significantly (42.9%, n=182) in comparison with control (16.8%, n=149, P<0.01). DRG Abeta neurons became less depolarized 2-4 h following Carg injection. After identifying the cell properties, Lucifer Yellow was injected and SP-like immunoreactivity (SP-LI) was then detected. A total of 17% of Abeta sensory neurons exhibited SP-LI in inflammatory cat. We also found in rat DRGs that the number of SP-LI positive large cells (>35 microm) was also significantly increased in Carg-treated DRG (11.8+/-1.2, n=8) compared with untreated DRG (1.8+/-0.8, n=8, P<0.01). In control cat, the topical use of SP in DRG did not induce any response of Abeta neurons. However, in Carg-treated cat, SP depolarized the membrane potential in most Abeta neurons (68.2%, n=22). L668,169, an antagonist of SP receptor, completely blocked the SP-induced responses. Furthermore, repeated application of SP did not induce obvious desensitization of Abeta neurons. These data suggest that peripheral inflammation increased the excitability, SP level and sensitivity of SP receptor of Abeta neurons. Therefore, we concluded that Abeta sensory neurons appear to contribute to inflammatory allodynia.

Action Potentials↗
PubMed2001

Neomycin blocks capsaicin-evoked responses in rat dorsal root ganglion neurons.

Small dorsal root ganglion (DRG) neurons are characterized by sensitivity to capsaicin. In acutely isolated rat DRG neurons, the effect of neomycin, one of the aminoglycoside antibiotics, on capsaicin-evoked current and voltage responses was examined using whole-cell patch-clamp recording. We showed for the first time that neomycin dose-dependently inhibited capsaicin-evoked currents with half-maximal inhibitory concentration at 130.60 microM (n=70). Under current-clamp condition, depolarization and firing rate evoked by capsaicin became weakened when neomycin was perfused to the neurons (n=10). Neomycin had no significant effect on the resting potentials of DRG neurons. These results suggest that neomycin could inhibit capsaicin-sensitive responses in small DRG neurons, which may contribute to neomycin-induced peripheral analgesia.

Analgesics↗
PubMed2001

Effects of isatin on rotational behavior and DA levels in caudate putamen in Parkinsonian rats.

Isatin was a potent endogenous monoamine oxidase (MAO) inhibitor that is more active against MAO-B than MAO-A. The acute effects of isatin on apomorphine (APO)-induced rotations were evaluated in Parkinsonian rats induced by 6-hydroxydopamine (6-OHDA) lesion. Furthermore, the effects of isatin on DA release in caudate putamen (CPu) of model and normal rats were monitored using fast cyclic voltammetry (FCV). The contents of monoamine transmitters and their metabolites in CPu of model and normal rats were also analyzed by high performance liquid chromatography with electrochemical detection after administration of isatin. Here we show that isatin (100 mg/kg, i.p.) apparently inhibited APO-induced rotations of Parkinsonian rats to 39.1+/-3.7% of the control (n=12), while it had no apparent effects on electrical stimuli-induced DA release either in normal rats or in model rats. In addition, the content of 5-hydroxytryptamine but not DA was increased in both normal rats and model rats after isatin (100 mg/kg, i.p.) was administered (P<0.01, n=6). The content of 5-hydroxyindole acetic acid was not changed. These results suggest that isatin cannot increase DA levels in rat CPu. Therefore, the effects of isatin on APO-induced rotations of our Parkinsonian rats could not attribute to its inhibition of DA catabolism as a MAO inhibitor.

Animals↗
PubMed2001

Novel purinergic sensitivity develops in injured sensory axons following sciatic nerve transection in rat.

Teased fibers were made from 153 spontaneous A afferents ending in sciatic nerve end neuromas of 3-14 days standing, 21 A afferents from intact sensory endings in the contralateral sciatic nerve, and 50 intact A afferents from the sciatic nerve in intact rats. Ninety-two percent of the injured fibers responded to adenosine 5'-triphosphate (ATP) (i.v.). However, few fibers from the contralateral nerve or nerves from intact animals responded to ATP. P2 receptor antagonist suramin or reactive blue 2 blocked the ATP-induced response in 76% of the fibers tested, whereas the P1 receptor antagonist aminophylline blocked the ATP-evoked effect in only 18% of the fibers tested. Sympathectomy did not affect the ATP-induced effects in injured axons. Close-arterial injection of ATP caused similar results as i.v. injection of ATP. The present study suggests that a novel purinergic sensitivity is developed at the injury site after sciatic nerve transection in rats, which may play a role in neuropathic pain under some conditions such as sympathetic activation.

Action Potentials↗
PubMed2001

Alteration of spontaneous firing rate of primary myelinated afferents by ATP in adjuvant-induced inflamed rats.

The action of adenosine 5'-triphosphate (ATP) on primary myelinated mechanosensitive afferents was investigated in adjuvant-induced inflamed rats. ATP injected intravenously increased the spontaneous firing rate in most of the A fibers from sciatic nerve innervating inflamed hindpaw, whereas it affected only a few units in normal rats. The effects of ATP were blocked or attenuated by competitive P2 receptor antagonist suramin or reactive blue 2 in most of the fibers tested. Degranulation of mast cells with compound 48/80 did not change the response rate of afferents to ATP in inflamed rats while chemical sympathectomy with 6-hydroxydopamine decreased it to some extent, suggesting an involvement of sympathetic efferents in mediating ATP effects. The results support the view that ATP could change the activity of large mechanosensitive afferents via P2 receptors under state of inflammation, which may be related to touch-evoked pain.

Action Potentials↗
PubMed2001

Buthus martensi Karsch agonist of skeletal-muscle RyR-1, a scorpion active polypeptide: antinociceptive effect on rat peripheral nervous system and spinal cord, and inhibition of voltage-gated Na(+) currents in dorsal root ganglion neurons.

The antinociceptive effect and potential antinociceptive mechanism of Buthus martensi Karsch agonist of skeletal-muscle RyR-1 (BmK AS-1), a scorpion venom derived neurotoxic polypeptide, have been investigated in rats. The results show that: (a) the withdrawal latency to rat plantar radiant heat was increased significantly by 100 and 150% after intrathecal injection of 0.6 and 1.2 microg doses; (b) C components of rat nociceptive flexion reflex were reduced to 72, 50 and 29% after intraplantar injection of 5, 10 and 20 microg doses; (c) both central (spinal cord) and peripheral antinociceptive effects of BmK AS-1 could not be reversed by naloxone; (d) tetrodotoxin-resistant (TTX-R) Na(+) current was depressed to 83.87+/-1.64, 64.73+/-5.43 and 15.85+/-17.63%, and tetrodotoxin-sensitive (TTX-S) Na(+) current was depressed to about 81.27+/-2.5, 49.08+/-8.09 and 9.03+/-12.34% with 0.2, 1.0 and 10 microg/ml BmK AS-1 measured using patch clamp recording in rat small dorsal root ganglion (DRG) neurons, respectively. The results indicate that BmK AS-1 may be a new component with potent antinociceptive activity mediated by modulating TTX-S and TTX-R Na(+) channels.

Animals↗
PubMed2001

Adenosine attenuates reperfusion-induced apoptotic cell death by modulating expression of Bcl-2 and Bax proteins.

This study tests the hypothesis that infarct reduction with adenosine (Ado) is associated with inhibition of apoptotic cell death by modulating expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins and reducing neutrophil accumulation. In three groups of dogs, the left anterior descending coronary artery was occluded for 60 min and reperfused for 6 h. Either saline (Control, n=8), Ado (140 microg/kg/min, n=8) or CGS21680, an adenosine A2A receptor analogue, (0.2 microg/kg/min, n=7) were infused during the first 2 h of reperfusion. Myocardial apoptosis was detected by histological TUNEL staining and DNA laddering. Expression of Bcl-2 and Bax proteins was analyzed using Western blot assay. Neutrophil localization was detected by immunohistochemistry with monoclonal anti-neutrophil CD18 antibody. There was no group difference in collateral blood flow (colored microspheres) during ischemia. Intra-left atrial administration of Ado and CGS21680 significantly decreased infarct size from 26+/-2% in Control to 13+/-1%* and 16+/-3%*, respectively. TUNEL positive cells in the peri-necrotic zone of the ischemic myocardium were also significantly reduced from 16+/-2% in Control group to 9+/-1%* and 10+/-2%*, respectively, consistent with the absence of DNA laddering in these two groups. Densitometrically, Ado and CGS21680 at reperfusion significantly increased the expression (% of normal myocardium) of downregulated Bcl-2 from 45+/-6% in Control group to 78+/-12%* and 69+/-10%*, respectively, and attenuated expression of upregulated Bax from 198+/-16% in Control group to 148+/-10%* and 158+/-12%*, respectively. Furthermore, the number of positive CD18 cells (mm(2) myocardium), which was significantly correlated with TUNEL positive cells in peri-necrotic zone, was significantly reduced from 403+/-42 in Control group to 142+/-18* in Ado group and 153+/-20%* in CGS21680 group, respectively. In conclusion, the present study suggests that inhibition of apoptosis by Ado at reperfusion involves alterations in anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins and neutrophil accumulation, primarily mediated by an adenosine A2A receptor. * P<0.05 v Control group.

Adenosine↗
PubMed2001

Electroplegia: an alternative to blood cardioplegia for arresting the heart during conventional (on-pump) cardiac operation.

BACKGROUND: Aortic cross-clamping is contraindicated in patients with severe atherosclerosis of the ascending aorta, and administration of chemical cardioplegia may be cumbersome in these patients. In this study, we demonstrate an alternative method of achieving cardioplegia by electrical stimulation of the vagus nerve. METHODS: In anesthetized canines, the left anterior descending coronary artery was reversibly ligated for 90 minutes, followed by cardiopulmonary bypass (CPB) and randomization to three groups (n = 8 each): (1) BCP group: 1 hour of intermittent hypothermic (4 degrees C) blood cardioplegia infusion; (2) CPB group: 1 hour of CPB alone; (3) EP group (group receiving electroplegia): 1 hour of intermittent vagal stimulation (total of 60 20-second electrical stimuli at 40 Hz, 6 to 10 V) with adjunctive pyridostigmine (0.5 mg/kg), verapamil (50 microg/kg), and propranolol (80 microg/kg) to potentiate hyperpolarization and suppress ectopic escape beats. RESULTS: The EP group achieved consistent intervals of arrest with 3.8 +/- 1.2 escape beats per 20-second stimulation period. After 2 hours of reperfusion off CPB, the left anterior descending coronary artery segmental shortening was reduced from baseline in all groups, but the segmental shortening recovered to a greater extent in the EP group than in either the CPB or BCP group (2.4% +/- 1.4% versus -1.3% +/- 1.3% versus -4.0% +/- 0.8%, p < 0.05). Infarct size (TTC stain, percentage of area at risk) was comparable among groups (EP: 20.9% +/- 4.7%; CPB: 29.6% +/- 3.2%; BCP: 25.1% +/- 5.7%). Postischemic left anterior descending coronary artery endothelial function (percent maximum relaxation to acetylcholine) was depressed in the EP group (68.6% +/- 7.6% versus 102.3% +/- 6.4%, p < 0.05), but was comparable versus nonischemic circumflex function in the BCP group (77.1% +/- 11.9% versus 100.4% +/- 10.0%, p = 0.15) and the CPB group (93.8% +/- 6.6% versus 93.3% +/- 6.6%). CONCLUSIONS: Electroplegia achieves elective intermittent cardiac arrest, avoids hypothermia, chemical cardioplegia, and aortic cross-clamping, with physiological outcomes comparable to blood cardioplegia.

Acetylcholine↗
PubMed2001

Brief pretreatment of radial artery conduits with phenoxybenzamine prevents vasoconstriction long term.

BACKGROUND: Radial artery bypass conduits are prone to early vasospasm or "string sign" with use of vasopressor therapy intraoperatively and postoperatively, causing increased resistance in coronary artery grafts. Current intraoperative treatment with papaverine fails to provide sustained inhibition of vasoconstriction. We tested the hypothesis that a 30-minute pretreatment of radial artery segments with the alpha-adrenergic antagonist phenoxybenzamine (PB) or the putative protein phosphatase 2,3-butadione monoxime (BDM) attenuates vasoconstriction induced by the vasopressors phenylephrine or norepinephrine for as long as 48 hours compared with papaverine. METHODS: Canine radial arteries were harvested, incubated in control buffer or solutions of papaverine 10(-6) M, BDM 10(-6) M or phenoxybenzamine 10(-6) M for 30 minutes, washed, and stored in drug-free culture medium for 2, 24, or 48 hours. After storage, constriction was induced by norepinephrine at incremental concentrations ranging from 0.7 to 3.5 micromol/L or by phenylephrine (0.300 to 1.5 micromol/L) with or without the inhibitors, and the degree of vasoconstriction was quantified in organ chambers. Responses to norepinephrine or phenylephrine were compared to constriction with receptor-independent potassium chloride KC1 (30 mmol/L). RESULTS: Maximum responses to phenylephrine and norepinephrine were comparable at 2, 24, and 48 hours after harvest in the control group (phenylephrine: 67% +/- 4%, 62% +/- 6%, 65% +/- 6% of KC1 response; norepinephrine: 75% +/- 4%, 62% +/- 1%, 58% +/- 7%, respectively). Papaverine failed to attenuate constriction to phenylephrine and norepinephrine 2, 24, or 48 hours posttreatment. Pretreatment with BDM did not reduce vasoconstriction responses to phenylephrine or norepinephrine 2 hours after incubation but did reduce constriction responses thereafter. In contrast, phenoxybenzamine completely attenuated constriction to both phenylephrine (19% +/- 8%, 1% +/- 4%, -12% +/- 4%) and norepinephrine (7.1% +/- 1%, -5% +/- 5%, -20% +/- 5%) at 2, 24, and 48 hours posttreatment, respectively. Phenoxybenzamine did not alter endothelial function relative to controls at any time point. CONCLUSIONS: Thirty-minute pretreatment of RA conduits with 10(-6) M phenoxybenzamine completely inhibits vasoconstriction to phenylephrine and norepinephrine for as long as 48 hours. Soaking radial artery grafts briefly in phenoxybenzamine solution before implantation may be effective in preventing postoperative vasospasm caused by two common alpha-adrenergic agonists used in postoperative hemodynamic management.

Animals↗
PubMed2001

The inhibitory effects of BmK IT2, a scorpion neurotoxin on rat nociceptive flexion reflex and a possible mechanism for modulating voltage-gated Na(+) channels.

Buthus martensi Karsch IT2 (BmK IT2), a scorpion neurotoxin, was found to display a biphasic inhibitory effect on the C component of the rat nociceptive flexion reflex by subcutaneous injection in vivo, and also on the total Na(+) currents of rat dorsal root ganglion neurons using whole-cell patch clamping. BmK IT2 blocked the tetrodotoxin-resistant (TTX-R) component of the Na(+) currents with a degree of selectivity. The partial block of the TTX-R Na(+) currents, brought about by 0.01 microg/microl BmK IT2, reversed less rapidly and completely than the partial block of the tetrodotoxin-sensitive (TTX-S) current brought about by the same concentration of BmK IT2. These results suggest that the inhibition of the rat nociceptive flexion reflex by BmK IT2 may be attributed to modulation of the different voltage-gated Na(+) channels.

Animals↗
PubMed2001

PKC regulates capsaicin-induced currents of dorsal root ganglion neurons in rats.

Capsaicin activates a non-specific cation conductance in a subset of dorsal root ganglion (DRG) neurons. The inward current and membrane potential of acutely isolated DRG neurons were examined using whole-cell patch recording methods. We report here that the current and voltage responses activated by capsaicin were markedly increased by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC). The mean current, after application of 0.3 microM PMA, was 153.5+/-5.7% of control (n=32) in Ca(2+)-free external solution and 181.6+/-6.8% of control (n=15) in standard external solution. Under current-clamp conditions, 0.3 microM PMA facilitated capsaicin-induced depolarization and action potential generation. Bindolylmaleimide I (BIM), a specific inhibitor of PKC activity, abolished the effect of PMA. In addition, capsaicin-evoked current was attenuated to 68.3+/-5.0% of control (n=13) by individual administration of 1 microM BIM in standard external solution, while 0.3 microM BIM did not have this effect. These data suggest that PKC can directly regulate the capsaicin response in DRG neurons, which could increase nociceptive sensory transmission and contribute to hyperalgesia.

Animals↗
PubMed2001

The involvement of glial cells in the development of morphine tolerance.

Glial response to chronic morphine treatment was examined by immunohistochemistry of glial fibrillary acidic protein (GFAP), a specific marker for astroglial cells. Systemic administration of morphine (50 mg/kg, i.p.) once daily for 9 consecutive days led to significant increase in GFAP immunostaining density in the spinal cord, posterior cingulate cortex and hippocampus but not in the thalamus. This increase was attributed primarily to hypertrophy of astroglial cells rather than their proliferation or migration. When chronic morphine (20 microg/2 microl, i.t.) was delivered in combination with fluorocitrate (1 nmol/1 microl, i.t.), a specific and reversible inhibitor of glial cells, spinal tolerance to morphine analgesia was partly but significantly attenuated as measured by behavioural test and the increase in spinal GFAP immunostaining was also greatly blocked. The present investigation provides the first evidence for the role of glial cells in the development of morphine tolerance in vivo.

Analgesics, Opioid↗
PubMed2001

Differential contributions of NMDA and non-NMDA receptors to spinal Fos expression evoked by superficial tissue and muscle inflammation in the rat.

The role of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the spinal cord in the transmission of nociceptive afferents from superficial tissue and muscle was studied by examining the effects of NMDA or non-NMDA receptor antagonists on Fos expression in the spinal dorsal horn. Muscle inflammation was induced by injection of turpentine oil into the gastrocnemius muscle, whereas superficial tissue inflammation was induced by an intraplantar injection of turpentine oil into the hindpaw. The NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP-5), the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) or normal saline were intrathecally administered 15 min before an intramuscular or intraplantar injection of turpentine oil. Muscle inflammation evoked expression of Fos-like immunoreactive neurons staining in neurons that were predominantly distributed in the middle portions of laminae I-II(outer) and the lateral portions of laminae V-VI of the ipsilateral dorsal horn at the spinal L(4)-L(5). DNQX, but not AP-5, significantly reduced the total number of Fos-like immunoreactive neurons evoked by muscle inflammation. In contrast, superficial tissue inflammation evoked expression of Fos-like immunoreactive neurons in the medial portions of laminae I-II(outer) and V-VI of the ipsilateral dorsal horn at the spinal L(4)-L(5) that was blocked by AP-5, but not by DNQX. Injection of normal saline did not influence the numbers of Fos-LI neurons. These results indicate that different glutamate receptors in the dorsal horn of the spinal cord may mediate nociceptive input from superficial tissue (particularly skin) and muscle. DNQX receptors may mediate transmission of nociceptive information originating in muscle, while NMDA receptors may preferentially mediate transmission of nociceptive information originating in skin.

Afferent Pathways↗
PubMed2001

Nitric oxide inhibits GABA-evoked current in dorsal root ganglion neuron via PKG-dependent pathway.

gamma-Aminobutyric acid (GABA) is considered a major inhibitory neurotransmitter in the generation of presynaptic inhibition at central terminals of primary afferent fiber (PAF), while it has also been established that nitric oxide (NO) may sensitize the terminals of nocisponsive PAFs and enhance neuropeptide release, possibly via mechanisms involving the activation of a cyclic guanidine monophosphate (cGMP)-dependent PKG. The present work was undertaken to explore the modulatory effect of sodium nitroprusside (SNP), a donor of NO, on GABA-evoked current of isolated adult rat dorsal root ganglion (DRG) neurons and the intracellular mechanism involved, by means of whole-cell patch clamp recording. The results showed that 1 mM SNP reversibly inhibited the inward current evoked by 0.1 mM GABA (-1.05 +/- 0.17nA vs. -0.63 +/- 0.11nA, n = 22, p < 0.01 or 0.1 mM muscimol a specific GABA(A) receptor agonist (-1.70 +/- 0.39 nA vs. -1.01 +/- 0.24 nA, n = 6, p < 0.05), which could be cancelled by simultaneous application of 1 mM methylene blue, an inhibitor of PKG. After preapplication of SNP with increasing concentrations 0.03, 0.1, 0.3, 1, and 3 mM), SNP inhibited both 0.1 mM GABA-evoked current (IC(50) = 0.2423 mM, n = 5) and 0.1 mM muscimol-evoked current (IC(50) = 0.3255 mM, n = 3) in DRG neurons in a dose-dependent manner. Therefore, it was suggested that PKG-dependent pathway may be involved in the NO-induced inhibition of GABA(A) receptor-mediated inward current in rat DRG neurons, which may be involved in the presynaptic disinhibition of nociceptive information induced by NO under certain conditions.

Animals↗
PubMed2001

The effects of Zn2+ on long-term potentiation of C fiber-evoked potentials in the rat spinal dorsal horn.

Tetanic stimuli of peripheral C fibers produces long-term potentiation (LTP) in the spinal cord, which may contribute to sensitization of spinal pain-sensitive neurons. Zn2+ is widely distributed in the central nervous system and has blocked (LTP) in the hippocampus. The present study examined the effects of Zn2+ on the induction and maintenance of C fiber-evoked LTP in the deep dorsal horn of spinalized rats in vivo. The sciatic nerve was stimulated by tetanic stimuli for inducing LTP. (1) Topical administration of Zinc chloride (15 microM) to the spinal cord 15 min before tetanic stimulation completely blocked the induction of LTP, but not the baseline C responses. When Zn2+ was given 2 h after induction of LTP, no significant effect occurred. (2) Chelation of Zn2+ by disodium calcium ethylene diaminetelraacetate (CaEDTA) (500 microM) resulted in no effect on LTP. (3) Coadministration of Zn2+ (15 microM) and N-methyl-D-aspartic acid (NMDA) (5 microM) significantly attenuated C fiber-evoked potentials, which was prevented by the NMDA receptor antagonist AP-5 (100 microM). The present results showed that Zn2+ may contribute to the modulation of the formation, but not the maintenance, of spinal LTP. NMDA receptors may be involved in Zn2+-induced modulation.

Afferent Pathways↗