Midazolam-induced hyperalgesia in rats: modulation via GABAA receptors at supraspinal level

Tatsuo, M.A.K.F.; Salgado, João Vinícius; Yokoro, C.M.; Duarte, Igor Dimitri Gama; Francischi, Janetti Nogueira de

doi:10.1016/s0014-2999(99)00096-5

Cited by 36 publications

(27 citation statements)

References 30 publications

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“…3 Tatsuo et al also reported that ip injection of midazolam 10 mg·kg -1 induced a significant decrease of tail flick latency and produced a long-lasting nociceptive effect in the formalin test, characterizing a hyperalgesic effect. 10 However, in the present study, we did not observe a hyperalgesic response. The only important difference between studies was the species of the rat.…”

Section: Discussioncontrasting

confidence: 81%

“…(1, 3, 10, 30, or (IC, 0,71 µg), (phase 2) avec l'administration intrathécale et de 11,6 µg (IC,2,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]3 µg), (phase 1) et de 52,2 µg (IC,18,7 …”

Section: Discussionunclassified

“…Tail withdrawal in response to thermal stimulation, or paw flinching and shaking in response to sc hind paw formalin injection were compared following intrathecal injection of midazolam (1,3,10,30, or 100 µg in 10 µL) or ip administration (3, 30, 300, or 3,000 µg in 300 µL). Saline 10 µL or 300 µL was used as a control.…”

Section: Methodsmentioning

confidence: 99%

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Analgesic effects of systemic midazolam: comparison with intrathecal administration

Nishiyama

2006

Can J Anesth/J Can Anesth

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Purpose: Midazolam has antinociceptive effects when administered intrathecally, while its effects associated with systemic administration remain controversial. In the present study, the antinociceptive properties of systemically vs intrathecally administered midazolam were investigated in a rat model of thermal and inflammatory pain. Methods:One hundred seventy-six (n = 8 animals per dose escalation) male Sprague-Dawley rats were instrumented with lumbar intrathecal catheters. Tail withdrawal in response to thermal stimulation, or paw flinching and shaking in response to sc hind paw formalin injection were compared following intrathecal injection of midazolam (1, 3, 10, 30, or 100 µg in 10 µL) or ip administration (3, 30, 300, or 3,000 µg in 300 µL). Saline 10 µL or 300 µL was used as a control. Behavioural side effects and motor disturbance were also examined.Results: Intrathecal administration of midazolam increased tail flick latency dose dependently (P < 0.05) with a 50% effective dose (ED50) of 1.60 µg, whereas ip administration did not increase latency. Both intrathecal and ip routes of administration decreased the number of paw flinches in both phases 1 and 2 of the formalin test (P < 0.05). The ED50s were 1.26 µg [confidence interval (CI), 0.35-3.18 µg], (phase 1) and 1.20 µg (CI, 0.29-3.71 µg), (phase 2) with intrathecal administration, and 11.6 µg (CI, 2.5-19.3 µg), (phase 1) and 52.2 µg (CI, 18.3-102.7 µg), (phase 2) with ip administration. Conclusion:Systemically administered midazolam induced antinociception for inflammatory pain only, while intrathecal administration elicited antinociceptive effects on both acute thermal and inflammatory-induced pain. (1, 3, 10, 30, or (IC, 0,71 µg), (phase 2) avec l'administration intrathécale et de 11,6 µg (IC,2,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]3 µg), (phase 1) et de 52,2 µg (IC,18,7 Objectif : Administré par voie intrathécale, le midazolam a des effets antinociceptifs, mais les effets d'une administration intrapéritonéale (ip) demeurent controversés. Dans la présente étude, nous avons vérifié les propriétés antinociceptives de l'administration générale vs intrathécale du midazolam chez un modèle expéri-mental de douleur thermique et inflammatoire chez le rat. Méthode : Un cathéter intrathécal lombaire a été mis en place chez 176 (n = 8 animaux par dose croissante) rats mâles SpragueDawley. Le retrait de la queue, en réaction à la stimulation thermique, ou le tressaillement et le tremblement de la patte en réaction à l'injection sc de formaline dans la patte arrière, ont été comparés à la suite d'une injection intrathécale de midazolam

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Section: Discussioncontrasting

confidence: 81%

Section: Discussionunclassified

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Analgesic effects of systemic midazolam: comparison with intrathecal administration

Nishiyama

2006

Can J Anesth/J Can Anesth

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“…Using less isoflurane also has the advantage of reducing the hazard of atmospheric pollution, and thus reducing environmental exposure to isoflurane and its metabolic products (Joubert, 1999). Both midazolam and isoflurane have been reported, though without full confidence for isoflurane, to produce central nervous system depression by potentiating the gamma-aminobutyric (GABA) receptor-channel complex (Larsen et al, 1998;Tatsuo et al, 1999). Midazolam probably reduces isoflurane MAC in an additive or synergistic manner through its activities at GABA receptor complex (Hendrickx et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Effects of midazolam on isoflurane minimum alveolar concentration in goats

Dzikiti

Stegmann

Dzikiti

et al. 2011

Small Ruminant Research

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a b s t r a c tThe effects of midazolam on the minimum alveolar concentration (MAC) of isoflurane in mechanically ventilated goats were evaluated. Six healthy goats (3 does and 3 wethers) were used in a randomized crossover design. General anaesthesia was induced with isoflurane. Endotracheal intubation was performed after which anaesthesia was maintained with isoflurane. Baseline isoflurane MAC was determined. The goats then received, on separate occasions, one of three midazolam treatments intravenously: bolus dose of 0.1 mg/kg followed by a maintenance dose of 0.1 mg/kg/h (Treatment LMID), bolus dose of 0.3 mg/kg followed by a maintenance dose of 0.3 mg/kg/h (Treatment MMID), bolus dose of 0.9 mg/kg followed by a maintenance dose of 0.9 mg/kg/h (Treatment HMID) intravenously. Isoflurane MAC was then re-determined for each midazolam treatment. The baseline [median (inter-quartile range)] isoflurane MAC in goats was 1.40 (1.38-1.41)%. Baseline isoflurane MAC was statistically significantly reduced (P < 0.05) following Treatment LMID, Treatment MMID and Treatment HMID by 16.8%, 35.1% and 54.7%, respectively. Quality of recovery from anaesthesia was good following all midazolam treatments. Midazolam, administered by constant rate infusion, significantly reduces isoflurane MAC in goats.

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“…However, it has also been reported that systemic administration of non-hypnotic doses of ethanol and barbiturates to rats results in reduction of tail-flick latency and this is abolished by non-convulsant doses of the GABA A receptor channel blocker picrotoxin, indicating involvement of GABAergic mechanisms in the mediation of ethanol-induced hyperalgesia [22]. Other studies have demonstrated that intracerebroventricular, but not intrathecal administration of these drugs induces a similar hyperalgesic state that is also reversed by a GABA A receptor blocker [45,46]. These results suggested that ethanol and some barbiturates might induce pain hypersensitivity (hyperalgesia) through acting on GABA A receptors at the supraspinal level, while they induce antinociception (analgesia) through acting on GABA A receptors at the spinal level.…”

Section: Where and How Ethanol Modulates Pain?mentioning

confidence: 92%

Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex

Geng

Wang

et al. 2016

Neurosci. Bull.

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Ethanol is widely known for its ability to cause dramatic changes in emotion, social cognition, and behavior following systemic administration in humans. Human neuroimaging studies suggest that alcohol dependence and chronic pain may share common mechanisms through amygdala-medial prefrontal cortex (mPFC) interactions. However, whether acute administration of ethanol in the mPFC can modulate pain perception is unknown. Here we showed that bilateral microinjections of ethanol into the prelimbic and infralimbic areas of the mPFC lowered the bilateral mechanical pain threshold for 48 h without influencing thermal pain sensitivity in adult rats. However, bilateral microinjections of artificial cerebrospinal fluid into the mPFC or bilateral microinjections of ethanol into the dorsolateral PFC (also termed as motor cortex area 1 in Paxinos and Watson's atlas of The Rat Brain. Elsevier Academic Press, Amsterdam, 2005) failed to do so, suggesting regional selectivity of the effects of ethanol. Moreover, bilateral microinjections of ethanol did not change the expression of either pro-apoptotic (caspase-3 and Bax) or anti-apoptotic (Bcl-2) proteins, suggesting that the dose was safe and validating the method used in the current study. To determine whether c-aminobutyric acid A (GABA A ) receptors are involved in mediating the ethanol effects, muscimol, a selective GABA A receptor agonist, or bicuculline, a selective GABA A receptor antagonist, was administered alone or co-administered with ethanol through the same route into the bilateral mPFC. The results showed that muscimol mimicked the effects of ethanol while bicuculline completely reversed the effects of ethanol and muscimol. In conclusion, ethanol increases mechanical pain sensitivity through activation of GABA A receptors in the mPFC of rats.

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Midazolam-induced hyperalgesia in rats: modulation via GABAA receptors at supraspinal level

Cited by 36 publications

References 30 publications

Analgesic effects of systemic midazolam: comparison with intrathecal administration

Analgesic effects of systemic midazolam: comparison with intrathecal administration

Effects of midazolam on isoflurane minimum alveolar concentration in goats

Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex

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