Nitroglycerin induces hyperalgesia in rats—a time-course study

Tassorelli, Cristina; Greco, Rosaria; Wang, Dechun; Sandrini, Maurizio; Sandrini, Giorgio; Nappi, Giuseppe

doi:10.1016/s0014-2999(03)01421-3

Cited by 98 publications

(94 citation statements)

References 19 publications

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“…Each animal was placed on the recording platform of the instrument where it was kept under slight, painless restraint, with its tail positioned on the radiant heat window. The movement of the tail from window of the beam of light to hit a sensor (latency in seconds) was automatically registered (7). Following the TFT, each rat was sacrificed with a lethal dose of chloral hydrate.…”

Section: Tail Flick Test (Tft)mentioning

confidence: 99%

“…This finding suggests that migraineurs bear a vulnerability to develop headache attacks following NTG administration as a specific trait linked to a supersensitivity of the pain system to this drug (5). Systemic administration of NTG has been used extensively as an animal model of migraine pain since it induces a condition of hyperalgesia in the rat and is associated with the activation of spinal cord and brain structures involved in nociception (6,7). In this model, we have shown that modulation of the endocannabinoid system (ECs) has an antihyperalgesic effect (8)(9)(10) and reduces the neuronal activation in the nucleus trigeminalis caudalis (NTC) and area postrema (8).…”

Section: Introductionmentioning

confidence: 99%

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Effects of peripheral FAAH blockade on NTG-induced hyperalgesia—evaluation of URB937 in an animal model of migraine

et al. 2015

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Background Systemic nitroglycerin (NTG) activates brain nuclei involved in nociceptive transmission as well as in neuroendocrine and autonomic functions in rats. These changes are considered relevant for migraine because NTG consistently provokes spontaneous-like migraine attacks in migraineurs. Several studies have suggested a relationship between the endocannabinoid levels and pain mediation in migraine. URB937, a peripheral inhibitor of fatty acid amide hydrolase (FAAH)—the enzyme that degrades anandamide, produces analgesia in animal models of pain, but there is no information on its effects in migraine. Aim We evaluated whether URB937 alters nociceptive responses in the animal model of migraine based on NTG administration in male rats, using the tail flick test and the plantar and orofacial formalin tests, under baseline conditions and after NTG administration. Furthermore, we investigated whether URB937 affects NTG-induced c-Fos expression in the brain. Results During the tail flick test, URB937 showed an antinociceptive effect in baseline conditions and it blocked NTG-induced hyperalgesia. URB937 also proved effective in counteracting NTG-induced hyperalgesia during both the plantar and orofacial formalin tests. Mapping of brain nuclei activated by NTG indicates that URB937 significantly reduces c-Fos expression in the nucleus trigeminalis caudalis and the locus coeruleus. Conclusions The data suggest that URB937 is capable of changing, probably via indirect mechanisms, the functional status of central structures that are important for pain transmission in an animal model of migraine.

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Section: Tail Flick Test (Tft)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of peripheral FAAH blockade on NTG-induced hyperalgesia—evaluation of URB937 in an animal model of migraine

et al. 2015

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“…Many animal studies have shown that NO contributes to the sensitization during inflammatory and neuropathic pain. The administration of a NO precursor or a NO donor decreases pain threshold causing hyperalgesia (Machelska et al 1998;Tassorelli et al 2003) and potentiates thermal hyperalgesia and tactile allodynia in neuropathic rats (Naik et al 2006). Inhibition of NO synthesis can considerably reduce both inflammatory and neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

Reversal of NO-induced nociceptive hypersensitivity by St. John’s wort and hypericin: NF-κB, CREB and STAT1 as molecular targets

Galeotti¹,

Ghelardini²

2012

Psychopharmacology

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Rationale Hypericum perforatum, popularly called St. John's wort (SJW), is a medicinal plant mainly used as antidepressant with a favorable safety profile than standard antidepressants. Some studies have also documented other SJW bioactivities, including pain modulation. Objectives The aim of this study was to demonstrate the capability of SJW to relieve nitric oxide (NO)-induced nociceptive hypersensitivity and identify the effective component. Methods Nociceptive hypersensitivity induced by administration of the NO donors nitroglycerin (GTN) and sodium nitroprusside (SNP) was assessed by cold and hot plate tests. The cellular pathways and molecular targets involved were investigated by Western blotting. Results GTN and SNP produced a prolonged allodynia and hyperalgesia in mice. A single oral administration of low doses of an SJW dried extract or purified hypericin reversed the NO donor-induced nociceptive behavior whereas hyperforin and flavoinoids were ineffective. Investigating into the cellular pathways involved, an increased CREB and STAT1 phosphorylation, and activation of NF-κB were detected within PAG and thalamus following NO donors' administration. These cellular events were prevented by SJW or hypericin. Since hypericin showed PKC blocking properties, a role of PKC as an upstream modulator of these transcription factors was hypothesized. NO donors increased expression and phosphorylation of protein kinase C (PKC) γ and ε isoforms, molecular events prevented by SJW or hypericin. Conclusions SJW reversed NO-induced nociceptive hypersensitivity through the blockade of a supraspinal signaling pathway involving a PKC-dependent CREB, STAT1 and NF-κB activation due to presence of hypericin. These data indicate SJW/hypericin as a therapeutic perspective for pain treatment.

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“…For example, intrathecal injection of NO donor nitroglycerin induced rapid and transient hyperalgesia in a dose-dependent manner, and accelerated the development and maintenance of hyperalgesia induced by sciatic nerve ligation [1,2]. Moreover, intrathecal administration of NOS inhibitors blocked pain behaviors and hyperalgesia in many pain models at the spinal cord level [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Fluorocitrate, an Inhibitor of Glial Metabolism, Inhibits the Up-Regulation of NOS Expression, Activity and NO Production in the Spinal Cord Induced by Formalin Test in Rats

Sun

Chen

et al. 2008

Neurochem Res

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Previous experiments have suggested that nitric oxide plays an important role in nociceptive transmission in the spinal cord. In order to explore the involvement of glia in the NO-mediated nociceptive transmission, the present study was undertaken to investigate the effect of fluorocitrate (FC), an inhibitor of glial metabolism, on NOS expression and activity and NO production in the spinal cord during the process of peripheral inflammatory pain and hyperalgesia induced by formalin test in rats. Sixty adult male Sprague-Dawley rats were randomly assigned into sham, formalin, formalin + normal saline (NS), and formalin + FC groups. The NOS expression, NOS activity and NO production was detected by NADPH-d histochemistry staining, NOS and NO assay kit, respectively. It was found that formalin test significantly up-regulated NOS expression and activity and NO production in the laminae I-II of the dorsal horn and the grey matter around the central canal in the lumbar spinal cord at 1 h after the formalin test. Selective inhibition of glia metabolism with intrathecal administration of FC (1 nmol) significantly inhibited the up-regulation in NOS expression and activity and NO production normally induced by the formalin test, which was represented with decreases in the number and density of the NADPH-d positive cells in the dorsal horn and grey matter around the central canal, and decrease in density of NADPH-d positive neuropil in the dorsal horn in formalin + FC group compared with formalin group. The results suggested that glia may be involved in the NO-mediated nociceptive transmission in the spinal cord.

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Nitroglycerin induces hyperalgesia in rats—a time-course study

Cited by 98 publications

References 19 publications

Effects of peripheral FAAH blockade on NTG-induced hyperalgesia—evaluation of URB937 in an animal model of migraine

Effects of peripheral FAAH blockade on NTG-induced hyperalgesia—evaluation of URB937 in an animal model of migraine

Reversal of NO-induced nociceptive hypersensitivity by St. John’s wort and hypericin: NF-κB, CREB and STAT1 as molecular targets

Fluorocitrate, an Inhibitor of Glial Metabolism, Inhibits the Up-Regulation of NOS Expression, Activity and NO Production in the Spinal Cord Induced by Formalin Test in Rats

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