Role of Spinal NO in Antiallodynic Effect of Intrathecal Clonidine in Neuropathic Rats 

1998 ◽  
Vol 89 (6) ◽  
pp. 1518-1523 ◽  
Author(s):  
Hui-Lin Pan ◽  
Shao-Rui Chen ◽  
James C. Eisenach
Keyword(s):  
Neuropathic Pain ◽  
Intrathecal Injection ◽  
No Donor ◽  
Before And After ◽  
Neuropathic Pain Model ◽  
Series Of Experiments ◽  
Intrathecal Clonidine ◽  
Intrathecal Space ◽  
Antiallodynic Effect

Background The role of spinal nitric oxide (NO) in neuropathic pain remains uncertain. Although intrathecal clonidine causes NO release in the spinal cord, the functional role of spinal NO in clonidine-produced analgesia has not been examined. The objectives of this study were to assess the role of spinal NO in maintenance of allodynia and to determine the role of spinal NO in the antiallodynic effect of intrathecal clonidine. Methods Allodynia was produced in rats by tight ligation of the left L5-L6 spinal nerves. Intrathecal catheters were inserted with tips in the lumbar intrathecal space. Mechanical allodynia was determined by application of von Frey filaments to the left hindpaw. In the first series of experiments, allodynia was assessed before and after intrathecal injection of saline, L-arginine, an NO donor (SNAP), two NO synthase inhibitors (TRIM and NMMA), or an NO scavenger (PTIO). In the second series of experiments, 20 microg of clonidine was injected intrathecally 15 min after intrathecal injection of saline, TRIM, NMMA, or PTIO. Results Allodynia was not affected significantly by intrathecal injection of L-arginine, SNAP, TRIM, NMMA, or PTIO. The antiallodynic effect produced by intrathecal injection of clonidine was attenuated significantly by pretreatment with TRIM, NMMA, or PTIO. Conclusions These results demonstrate that spinal NO neither contributes significantly to maintenance of allodynia nor produces detectable antiallodynic effect in this neuropathic pain model. Furthermore, this study provides functional evidence that spinal NO plays an important role in the antiallodynic effect of intrathecal clonidine in neuropathic pain.

Antiallodynic Effect of Intrathecal Neostigmine Is Mediated by Spinal Nitric Oxide in a Rat Model of Diabetic Neuropathic Pain

2001 ◽  
Vol 95 (4) ◽  
pp. 1007-1012 ◽  
Author(s):  
Shao-Rui Chen ◽  
Ghous M. Khan ◽  
Hui-Lin Pan
Keyword(s):  
Nitric Oxide ◽  
Neuropathic Pain ◽  
Rat Model ◽  
Acetylcholinesterase Inhibitor ◽  
Intrathecal Injection ◽  
Diabetic Neuropathic Pain ◽  
Endogenous Nitric Oxide ◽  
Antiallodynic Effect ◽  
Von Frey Filaments

Background Intrathecal administration of acetylcholinesterase inhibitors produces antinociception in both animals and humans, but their effect on diabetic neuropathic pain has not been studied. In the current study, we determined the antiallodynic effect of intrathecal injection of an acetylcholinesterase inhibitor, neostigmine, in a rat model of diabetic neuropathic pain. In addition, since acetylcholine can increase release of nitric oxide in the spinal cord, we studied the role of spinal endogenous nitric oxide in the action of intrathecal neostigmine in diabetic neuropathic pain. Methods Rats were rendered diabetic with an intraperitoneal 50-mg/kg injection of streptozotocin. Intrathecal catheters were inserted, with tips in the lumbar intrathecal space. Mechanical allodynia was determined by application of von Frey filaments to the hind paw. We first determined the dose-dependent effect of intrathecal neostigmine on allodynia. The role of spinal nitric oxide in the action of intrathecal neostigmine was then examined through intrathecal treatments with a neuronal nitric oxide synthase inhibitor (TRIM), a nitric oxide scavenger (PTIO), L-arginine, or D-arginine. Results The diabetic rats developed a sustained tactile allodynia within 4 weeks after streptozotocin injection. Intrathecal injection of 0.1-0.5 microg neostigmine dose-dependently increased the withdrawal threshold in response to application of von Frey filaments. Intrathecal pretreatment with 30 microg TRIM or 30 microg PTIO abolished the antiallodynic effect of intrathecal neostigmine. Furthermore, the inhibitory effect of TRIM on the action of intrathecal neostigmine was reversed by intrathecal injection of 100 microg L-arginine but not D-arginine. Conclusions Intrathecal neostigmine produces a profound analgesic effect in a rat model of diabetic neuropathic pain. Spinal endogenous nitric oxide contributes to the analgesic action of intrathecal neostigmine in this rat model of diabetic neuropathic pain.

scholarly journals MiR-1906 attenuates neuropathic pain in rats by regulating the TLR4/mTOR/ Akt signaling pathway

2019 ◽  
Vol 10 (1) ◽  
pp. 175-179 ◽  
Author(s):  
Xianhai Fang ◽  
Huacheng Zhou ◽  
Shaopeng Huang ◽  
Jinfeng Liu
Keyword(s):  
Neuropathic Pain ◽  
Western Blotting ◽  
Rat Model ◽  
Latency Period ◽  
Enzyme Linked Immunosorbent Assay ◽  
Withdrawal Latency ◽  
Proinflammatory Mediators ◽  
Neuropathic Pain Model ◽  
Pathway Regulation

Abstract Background This study determined the role of miR-1906 in neuropathic pain and proliferation in neuronal cells using a chronic constriction injury (CCI)-induced neuropathic pain (NP) rat model. Methodology NP was induced by CCI. Animals were divided into a sham group, an NP group, and a miR-1906 mimic group, which received 500 nmol/kg of a miR-1906 mimic intrathecally for 10 consecutive days following surgery. The effect of miR-1906 agomir was determined by estimating the thermal and mechanical withdrawal latency; an enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proinflammatory mediators. Western blotting and reverse-transcription polymerase chain reaction (RT-PCR) were used to determine protein expression in the spinal tissues of the CCI-induced neuropathic pain rat model. Results Administration of miR-1906 agomir increased the mechanical and thermal withdrawal latency period and the levels of inflammatory mediators compared with the NP group. Western blotting showed that treatment with miR-1906 agomir attenuated the levels of Akt, mTOR, TLR-4, and PI3K proteins in the spinal tissues of the CCI-induced neuropathic pain model. TLR-4 and NF-κB gene expression was lower in the miR-1906 agomir group than in the NP group. Conclusion miR-1906 gene stimulation reduced neuropathic pain by enhancing Akt/nTOR/PI3K and TLR-4/NF-κB pathway regulation.

scholarly journals Antiallodynic effect of intrathecal resiniferatoxin on neuropathic pain model of chronic constriction injury

2017 ◽  
Vol 77 (4) ◽  
pp. 317-322 ◽  
Author(s):  
Julia Risso Parisi ◽  
Ana Laura Martins de Andrade ◽  
Josie Resende Torres Silva ◽  
Marcelo Lourenço Silva
Keyword(s):  
Neuropathic Pain ◽  
Chronic Constriction Injury ◽  
Pain Model ◽  
Neuropathic Pain Model ◽  
Antiallodynic Effect

Adenosine depletion alters postictal hypoxic cerebral vasodilation in the newborn pig

1998 ◽  
Vol 274 (5) ◽  
pp. H1495-H1501 ◽  
Author(s):  
R. J. DiGeronimo ◽  
C. A. Gegg ◽  
S. L. Zuckerman
Keyword(s):  
Sodium Nitroprusside ◽  
Seizure Activity ◽  
State Farm ◽  
Dilatory Response ◽  
Before And After ◽  
Significant Attenuation ◽  
Series Of Experiments ◽  
Cerebral Vasodilation ◽  
Pial Vessel

Altered postictal cerebral blood flow dilatory responses may contribute to brain injury following neonatal seizures. We developed an initial series of experiments to characterize the effects of seizure activity on cerebral vascular dilatory responses during the immediate postictal period. Significant attenuation of postictal hypoxic cerebral vasodilation was noted. We hypothesize that this diminished cerebral dilator response to hypoxia involves depletion of adenosine (Ado) activity resulting from seizure ictus. Additional experiments were designed to evaluate whether the altered postictal responses were related to a depletion of Ado stores or a decreased response to Ado in the postictal state. Farm-bred piglets were equipped with closed cranial windows. Responses to hypercapnia (10% CO2), hypoxia (fractional inspired O2 = 0.10), and topical sodium nitroprusside (10−6M) were compared before and after bicuculline-induced seizures (1 mg/kg). Hypoxia-induced cerebral vasodilation was significantly attenuated in the first 90 min postictal (control: 56.5 ± 6%, 10 min postictal: 6.3 ± 2%, 60 min postictal: 21.7 ± 6%, and 90 min postictal: 21.6 ± 5%; P < 0.01), whereas the dilator responses to hypercapnia and topical sodium nitroprusside remained intact. In a separate group of piglets, both a dilating (10−5 M) and a nondilating concentration of Ado (10−11 M) were topically administered postictally to measure their effects on pial vessel dilatory response to hypoxia. Dilation to topical Ado (10−5 M) was not altered postictally compared with control. Ado (10−11 M) restored hypoxia-induced vasodilation to preseizure control values in the immediate postictal period (control: 51.0 ± 8%, postictal: 46.7 ± 8%; P > 0.05). Postictal administration of Ado will restore hypoxia-induced cerebral vasodilation in piglets even when a nondilating concentration is employed. This suggests that depletion of Ado with seizure activity is a mechanism for the loss of postictal cerebral vasodilation to hypoxia, and the role of Ado in hypoxic cerebral vasodilation is permissive.

Role of nitric oxide and cAMP in prostaglandin-induced pial arterial vasodilation

1995 ◽  
Vol 268 (4) ◽  
pp. H1436-H1440 ◽  
Author(s):  
W. M. Armstead
Keyword(s):  
Nitric Oxide ◽  
Topical Administration ◽  
No Donor ◽  
Cyclic Monophosphate ◽  
Cranial Window ◽  
Pial Artery ◽  
Before And After ◽  
Arterial Dilation ◽  
Synthase Inhibitor

The present study was designed to investigate the role of nitric oxide (NO), guanosine 3',5'-cyclic monophosphate (cGMP), and adenosine 3',5'-cyclic monophosphate (cAMP) in the vasodilator response to prostaglandin (PG)I2 and PGE2 in newborn pigs equipped with a closed cranial window. PGI2 (1–100 ng/ml) produced pial arterial dilation that was blunted by nitro-L-arginine (L-NNA, 10(-6) M), an NO synthase inhibitor (9 +/- 1 vs. 2 +/- 1%, 21 +/- 1 vs. 5 +/- 3% for 1 and 100 ng/ml PGI2 respectively, n = 6; means +/- SE). PGI2-induced vasodilation was associated with increased cortical periarachnoid cerebrospinal fluid (CSF) cGMP, and these changes in cGMP were blocked by L-NNA (386 +/- 8 and 1,054 +/- 30 fmol/ml vs. 266 +/- 6 and 274 +/- 4 fmol/ml for control and PGI2 100 ng/ml before and after L-NNA respectively, n = 6). In contrast, PGI2-associated changes in CSF cAMP were unchanged by L-NNA (1,021 +/- 25 and 2,703 +/- 129 fmol/ml vs. 980 +/- 23 and 2,636 +/- 193 fmol/ml for control, PGI2 100 ng/ml before and after L-NNA, respectively, n = 6). PGE2 elicited similar changes in pial artery diameter and cyclic nucleotides; vasodilation and changes in CSF cGMP also being similarly inhibited by L-NNA. After L-NNA, topical administration of the NO donor sodium nitroprusside (SNP, 10(-9) M) increased pial artery diameter up to the resting level before L-NNA and partially restored the vasodilation elicited by PGI2 and PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)

Antipyretic role of the NO-cGMP pathway in the anteroventral preoptic region of the rat brain

2002 ◽  
Vol 282 (2) ◽  
pp. R584-R593 ◽  
Author(s):  
Alexandre A. Steiner ◽  
Jose Antunes-Rodrigues ◽  
Samuel M. McCann ◽  
Luiz G. S. Branco
Keyword(s):  
Soluble Guanylate Cyclase ◽  
Early Stage ◽  
Body Core Temperature ◽  
Preoptic Region ◽  
No Donor ◽  
Cgmp Pathway ◽  
Before And After ◽  
Body Core ◽  
Nitrite Nitrate

We tested the hypothesis that nitric oxide (NO) acts in the anteroventral preoptic region (AVPO) modulating fever. To this end, body core temperature (Tc) of rats was monitored by biotelemetry before and after pharmacological modulation of the NO pathway. Nitrite/nitrate and cGMP in the anteroventral third ventricular region (AV3V), where the AVPO is located, were also determined. Intra-AVPO microinjection of the NO synthase (NOS) inhibitor N G-monomethyl-l-arginine (l-NMMA, 12.5 μg) did not affect basal Tc, but it enhanced the early stage of lipopolysaccharide (LPS) fever, indicating that NO plays an antipyretic role in the AVPO. In agreement, intra-AVPO microinjection of the NO donor sodium nitroprusside (5 μg) reduced Tc. The antipyretic effect of NO seems to be mediated by cGMP because 1) NO has been shown to activate soluble guanylate cyclase, 2) intra-AVPO microinjection of 8-bromo-cGMP (8-BrcGMP) reduced Tc, and 3) the changes in AV3V levels of nitrite/nitrate and cGMP were similar in the course of fever. Additionally, we observed that nitrite/nitrate and cGMP levels decreased in the AV3V after, but not before, the onset of LPS fever, showing that the activity of the NO-cGMP pathway is reduced in the AV3V after intraperitoneal LPS, a mechanism that could contribute to the genesis and maintenance of fever. It was also observed that the efficacy of 8-BrcGMP in reducing Tc in the AVPO is increased after LPS, emphasizing that the NO-cGMP pathway is antipyretic. This response could explain why intra-AVPOl-NMMA enhanced the early stage of LPS fever, even though the activity of the NO pathway before the onset of fever was unchanged. In summary, these data support an antipyretic role of the NO-cGMP pathway in the AVPO.

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