Central GABA‐ergic systems and analgesia

DeFeudis, F.V.

doi:10.1002/ddr.430030102

Cited by 21 publications

(2 citation statements)

References 129 publications

(46 reference statements)

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“…74,75 The antinociceptive effects of both GABA A and GABA B receptor agonists are known to involve activation or inhibition of other neurotransmitter or neuromodulator pathways 76 and it is evident that central GABAergic systems are involved in opioid-mediated analgesia. 77 Thus, it is possible that administration of GABA receptor agonists in combination with other agents may yield GABA receptor-related therapies for the treatment of acute and chronic pain. 76 Specific modulators of GABA A receptor function possess advantages that, in addition to possessing analgesic properties, can mediate anxiolytic-like actions by virtue of their ability to modulate α2 and possibly α3 GABA A receptors.…”

Section: Discussionmentioning

confidence: 99%

<p>Antinociceptive Effect of the Citrus Flavonoid Eriocitrinon Postoperative Pain Conditions</p>

Alghamdi¹

2020

JPR

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Background: Postoperative pain remains a major clinical problem as there are limited analgesic strategies that have been proven to be effective in preventing and relieving this type of pain. Natural products, including flavonoids, have distinct pharmacological properties and play an important role in the discovery of analgesic drugs. Materials and Methods: In this study, the flavonoid eriocitrin (eriodictyol 7-O-rutinoside), which is the main flavonoid in lemon fruit (Citrus limon), was mechanistically investigated for its prospective antinociceptive effect in a mouse model of postoperative pain. The antinociceptive property was evaluated by utilizing both tonic (acetic acid-induced writhing behavior) and phasic (hot-plate) nociception modalities. The hindpaw incisional surgery was performed and hyperalgesia was assessed using von Frey filaments. Results: The tested doses of eriocitrin significantly attenuated (P<0.01, P<0.001) the chemically-induced tonic visceral nociception (5, 10, 15, and 30 mg/kg) and acute phasic thermal nociception (10, 15, and 30 mg/kg). A significant dose-dependent reduction in the incisional nociceptive hyperalgesia was exhibited by eriocitrin, with a marked antinociception observed at doses of 15 mg/kg (P<0.05 during 30-60 minutes) and 30 mg/kg (P<0.05, P<0.01 during 30-120 minutes). Conclusion: The antinociceptive effect of eriocitrin (30 mg/kg) was strongly blocked by the antagonists of the opioid receptor, naltrexone, and GABA A receptor, bicuculline, thereby suggesting the involvement of opioidergic and GABAergic mechanisms in the nociception, reducing proclivity of eriocitrin during transmission of incisional nociception. These results concluded that eriocitrin has a potent antinociceptive effect in postoperative pain conditions, probably mediated through opioid and GABA A receptors.

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Section: Discussionmentioning

confidence: 99%

<p>Antinociceptive Effect of the Citrus Flavonoid Eriocitrinon Postoperative Pain Conditions</p>

Alghamdi¹

2020

JPR

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“…These include not only affinity for GABA A but also GABA B receptors in addition to modification of GABA uptake [ 66 ]. The antinociceptive effects of both GABA A and GABA B receptor agonists are known to involve activation or inhibition of other neurotransmitter or neuromodulator pathways [ 64 ] and it is evident that central GABAergic systems are involved in opioid-mediated analgesia [ 67 ]. Thus, it is possible that administration of GABA receptor agonists in combination with other agents may yield GABA receptor-related therapies for the treatment of acute and chronic pain [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms

Aman¹,

Subhan²,

Shahid³

et al. 2016

BMC Complement Altern Med

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Background: Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic properties. Passiflora incarnata L. methanolic extract (PI-ME) was evaluated in an animal model of streptozotocininduced diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive, anxiolytic and sedative activities in mice in order to examine possible underlying mechanisms. Methods: PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate and GC-MS analysis. The antinociceptive property was evaluated using the abdominal constriction assay and hot plate test. The anxiolytic activity was performed in a stair case model and sedative activity in an open field test. The antagonistic activities were evaluated using naloxone and/or pentylenetetrazole (PTZ). PI-ME was evaluated for prospective anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia. Results: GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide (9-octadecenamide), palmitic acid (hexadecanoic acid) and 3-hydroxy-dodecanoic acid, among other active constituents. In the abdominal constriction assay and hot plate test, PI-ME produced dose dependant, naloxone and pentylenetetrazole reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms. In the stair case test, PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was observed. The rearing incidence was diminished by PI-ME at all tested doses and in the open field test, PI-ME decreased locomotor activity to an extent that was analagous to diazepam. The effects of PI-ME were antagonized by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative activities. In the streptozotocin-induced neuropathic nociceptive model, PI-ME (200 and 300 mg/kg) exhibited static and dynamic anti-allodynic effects exemplified by an increase in paw withdrawal threshold and paw withdrawal latency. PI-ME relieved only the dynamic component of vulvodynia by increasing flinching response latency.

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Evaluation of THIP in standard tests for analgesic activity: Occurrence of antinociception and hyperalgesia

Hynes

David

Frederickson

et al. 1984

Drug Development Research

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Archer: Evaluation of THlP in standard tests for analgesic activity: Occurrence of antinociception and hyperalgesia. Drug Dev. Res. 4:405-419, 1984. THlP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), a structurally rigid analog of the GABAagonist muscimol, was investigated for antinociceptive activity in a variety of preclinical tests for analgesic activity. Antinociceptive activity was observed in the mouse writhing, mouse hot plate, rat tail flick, rat inflamed paw, and monkey shock titration tests. In the mouse writhing, mouse hot plate, and rat tail jerk experiments, periods of significant hyperalgesia were noted either prior to or following the occurrence of THIP-induced antinociception. At those times when an antinociceptive effect of THlP could be demonstrated in the test systems employed in this study, a variety of unfavorable effects were noted including sedation, ataxia, myoclonic jerks, and vomiting. These side-effects of THlP first appeared near the dose that produced antinociception in 50% of the animals (EDs0 value) and became progressively more intense as the dose increased. Neither the narcotic antagonist naloxone, the cholinergic antagonist atropine, nor the GABA-antagonists bicuculline or picrotoxin blocked the antinociceptive activity of THIP. The synthesis of prostaglandins was not inhibited by THIP. The antinociceptive activity of THlP is an interesting lead in the search for a novel analgesic that lacks the undesirable effects of opiates. However, the occurrence of hyperalgesia and marked side-effects at doses near the effective analgesic dose may limit THIP's therapeutic potential.

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Central GABA‐ergic systems and analgesia

Cited by 21 publications

References 129 publications

<p>Antinociceptive Effect of the Citrus Flavonoid Eriocitrinon Postoperative Pain Conditions</p>

<p>Antinociceptive Effect of the Citrus Flavonoid Eriocitrinon Postoperative Pain Conditions</p>

Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms

Evaluation of THIP in standard tests for analgesic activity: Occurrence of antinociception and hyperalgesia

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