Participation of neuronal nitric oxide synthase in experimental neuropathic pain induced by sciatic nerve transection

Chacur, Marucia; Matos, Rhowena Jane Barbosa de; Alves, Adilson da Silva; Rodrigues, A. C.; Gutierrez, Vanessa Pacciari; Cury, Yara; Britto, Luiz Roberto Giorgetti de

doi:10.1590/s0100-879x2010007500019

Cited by 37 publications

(24 citation statements)

References 32 publications

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“…In a rat model of spinal cord ischemia, L-NAME, and the selective nNOS inhibitors 6-NI (6-nitroindazole) and 7-NI given IP decreased the vocalization threshold in response to mechanical stimulation of the skin innervated by the injured spinal cord segment 10. 7-NI administered by lumbar puncture to rats with sciatic nerve transection also decreased mechanical hyperalgesia and allodynia 12. This study also showed nerve-injured rats had increased expression of nNOS in the spinal cord as shown by immunohistochemistry, real-time polymerase chain reaction (PCR) and immunoblotting.…”

Section: Discussionmentioning

confidence: 99%

“…An electrophysiological study found that administration of the nonselective NOS inhibitor N ω -nitro-L-arginine methyl ester (L-NAME) attenuated ongoing discharges in the DRG in a sciatic nerve axotomy model 9. Finally, behavioral studies have shown that L-NAME and selective nNOS inhibitors relieve pain hypersensitivity in various nerve injury models,10–12 while nitric oxide precursors and donors enhance hypersensitivity 13…”

Section: Introductionmentioning

confidence: 99%

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The selective neuronal nitric oxide synthase inhibitor 7-nitroindazole has acute analgesic but not cumulative effects in a rat model of peripheral neuropathy

Dableh¹,

Henry²

2011

JPR

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Chronic neuropathic pain that may arise from various nerve injuries or insults remains notoriously difficult to manage. The neuronal isoform of the enzyme nitric oxide synthase (nNOS) has been shown to be involved in the spinal transmission of nociception in animal models of chronic pain. The aim of this study is to evaluate the effect of single dose and repeated administration of a selective nNOS inhibitor. Rats were unilaterally implanted with a 2-mm polyethylene cuff around the sciatic nerve. Paw withdrawal thresholds were measured using von Frey filament stimulation. Rats were given 10, 20, or 30 mg/kg of 7-nitroindazole (7-NI), or vehicle, on days 2, 5, and 7 after model induction, respectively. Paw withdrawal thresholds were measured before and at 30 and 60 min after injection. 7-NI significantly increased paw withdrawal thresholds at 60 min at the 20 and 30 mg/kg dosages. In the second part of this study, rats were given 20 mg/kg 7-NI daily for five days starting immediately after cuff implantation (days 0 to 4), and the cuff was removed on day 4. Withdrawal thresholds were measured intermittently over a 24-day observation period. No differences in withdrawal thresholds were observed between drug and vehicle-treated rats. Therefore, early and repeated administration of 7-NI did not affect the development or progression of the model. In conclusion, inhibition of nNOS had an analgesic but not a pre-emptive effect in this model of peripheral neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The selective neuronal nitric oxide synthase inhibitor 7-nitroindazole has acute analgesic but not cumulative effects in a rat model of peripheral neuropathy

Dableh¹,

Henry²

2011

JPR

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“…Neuronal NOS (nNOS, type 1 NOS) is one forms of NOS [7]. Over the past decades, by using inhibitors of NO biosynthesis, NO donors and animal nociceptive models, knowledge of the role of NO in types of pain has been discovered both in central and peripheral system [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Role of laser fluence in protein synthesis of cultured DRG neurons following low-level laser irradiation

et al. 2014

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Low-level lasers have been used to relieve pain in clinical for many years. But the mechanism is not fully clear. In animal models, nitric oxide (NO) has been reported involving in the transmission and modulation of nociceptive signals.So the objective of this study was to establish whether low-level laser with different fluence could stimulate the production of nitric oxide synthese (NOS), which produces NO in cultured primary dorsal root ganglion neurons (DRG neurons). The primary DRG neurons were isolated from healthy Sprague Dawley rats (8-12 weeks of age) and spread on 35 mm culture dishes specially used for confocal microscopy. 24 hours after spreading, cells were irradiated with 658 nm laser for two consecutive days at the energy density of 20, 40, 60 and 80 mJ· cm -2 respectively. Control groups were not exposed to the laser, but were kept under the same conditions as the irradiated ones. The synthesis of NOS after laser irradiation was detected by immunofluorescence assay, and the changes of NOS were evaluated using confocal microscopy and Image J software. The results showed that all the laser fluence could promote the production of NOS in DRG neurons, especially the 60 mJ· cm -2 . These results demonstrated that low-level laser irradiation could modify protein synthesis in a dose-or fluence-dependent manner, and indicated that low-level laser irradiation might achieve the analgesic effect through modulation of NO production.

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“…NO regulates a range of physiological and pathophysiological process, such as respiration [7,8], cell migration [9] and apoptosis [10,11]. Over the past decades, by using inhibitors of NO biosynthesis, NO donors and animal nociceptive models, knowledge of the role of NO in types of pain has been discovered both in central and peripheral system [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Determination of nitric oxide mediating intracellular Ca²⁺release on neurons based on confocal microscopy imaging

Zheng

Wang

et al. 2014

SPIE Proceedings

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The gas NO is a ubiquitous intercellular messenger that modulates a wide range of physiological and pathophysiological functions. But few studies were made to study the role of NO in the Ca 2+ release in dorsal root ganglion (DRG) neurons by confocal microscopy. Thus the objective of this study was to assess if NO has a role in Ca 2+ signaling in DRG neurons using confocal microscopy combined with special fluorescence probe Fluo-3/AM. A 100 μM concentration of the NO donors (Sodium Nitroprusside, Dihydrate, SNP) and NO synthase inhibitor (N G -Monomethyl-L-arginine, Monoacetate salt, L-NMMA) was used in the study. Results showed that the fluorescence intensity increased rapidly after injecting SNP, which indicated that SNP could enhance intracellular Ca 2+ release. And the fluorescence intensity shrank gradually with time and kept at a low level for quite a long period after loading with L-NMMA which indicated that L-NMMA could block intracellular Ca 2+ release. All these results demonstrated that NO was involved in the regulation of intracellular Ca 2+ release in the DRG neurons.

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Participation of neuronal nitric oxide synthase in experimental neuropathic pain induced by sciatic nerve transection

Cited by 37 publications

References 32 publications

The selective neuronal nitric oxide synthase inhibitor 7-nitroindazole has acute analgesic but not cumulative effects in a rat model of peripheral neuropathy

The selective neuronal nitric oxide synthase inhibitor 7-nitroindazole has acute analgesic but not cumulative effects in a rat model of peripheral neuropathy

Role of laser fluence in protein synthesis of cultured DRG neurons following low-level laser irradiation

Determination of nitric oxide mediating intracellular Ca²⁺release on neurons based on confocal microscopy imaging

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Participation of neuronal nitric oxide synthase in experimental neuropathic pain induced by sciatic nerve transection

Cited by 37 publications

References 32 publications

The selective neuronal nitric oxide synthase inhibitor 7-nitroindazole has acute analgesic but not cumulative effects in a rat model of peripheral neuropathy

The selective neuronal nitric oxide synthase inhibitor 7-nitroindazole has acute analgesic but not cumulative effects in a rat model of peripheral neuropathy

Role of laser fluence in protein synthesis of cultured DRG neurons following low-level laser irradiation

Determination of nitric oxide mediating intracellular Ca2+release on neurons based on confocal microscopy imaging

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Determination of nitric oxide mediating intracellular Ca²⁺release on neurons based on confocal microscopy imaging