Analgesic and Hyperalgesic Effects of Midazolam

Niv, David; Davidovich, Shaul; Geller, Eran; Urca, Gideon

doi:10.1213/00000539-198812000-00010

Cited by 53 publications

(26 citation statements)

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“…However, the effects of midazolam on nociception may depend on the route of administration, with analgesia observed after spinal or epidural application, but not after systemic administration of this agent. [18][19][20] Also, in our study, intravenous administration of midazolam did not enhance the analgesic effect of intrathecal injection. Finally, the use of dexmedetomidine premedication before spinal anesthesia seems to offer clinical advantages compared with midazolam premedication, since dexmedetomidine provides additional analgesia.…”

Section: Discussionmentioning

confidence: 72%

Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anesthesia

Kaya

Yavaşçaoğlu

Türker

et al. 2009

Can J Anesth/J Can Anesth

118

126

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Section: Discussionmentioning

confidence: 72%

Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anesthesia

Kaya

Yavaşçaoğlu

Türker

et al. 2009

Can J Anesth/J Can Anesth

118

126

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“…Analgesia, hyperalgesia or no effect has been attributed to these drugs (13)(14)(15)(16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

Hyperalgesic effect induced by barbiturates, midazolam and ethanol: pharmacological evidence for GABA-A receptor involvement

Tatsuo

Yokoro²,

Salgado³

et al. 1997

Braz J Med Biol Res

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The involvement of GABA-A receptors in the control of nociception was studied using the tail-flick test in rats. Non-hypnotic doses of the barbiturates phenobarbital (5-50 mg/kg), pentobarbital (17-33 mg/ kg), and thiopental (7.5-30 mg/kg), of the benzodiazepine midazolam (10 mg/kg) or of ethanol (0.4-1.6 g/kg) administered by the systemic route reduced the latency for the tail-flick response, thus inducing a 'hyperalgesic' state in the animals. In contrast, non-convulsant doses of the GABA-A antagonist picrotoxin (0.12-1.0 mg/kg) administered systemically induced an increase in the latency for the tail-flick response, therefore characterizing an 'antinociceptive' state. Previous picrotoxin (0.12 mg/kg) treatment abolished the hyperalgesic state induced by effective doses of the barbiturates, midazolam or ethanol. Since phenobarbital, midazolam and ethanol reproduced the described hyperalgesic effect of GABA-A-specific agonists (muscimol, THIP), which is specifically antagonized by the GABA-A antagonist picrotoxin, our results suggest that GABA-A receptors are tonically involved in the modulation of nociception in the rat central nervous system.

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“…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%

“…1,2 However, intraperitoneally administered midazolam may be associated with hyperalgesia, 3 while it potentiates isoflurane-induced antinociception at doses where no effect is seen with midazolam alone. 4 Therefore, it is uncertain as to whether systemically administered midazolam is analgesic or hyperalgesic.…”

Section: Objectifmentioning

confidence: 99%

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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Analgesic and Hyperalgesic Effects of Midazolam

Cited by 53 publications

References 0 publications

Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anesthesia

Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anesthesia

Hyperalgesic effect induced by barbiturates, midazolam and ethanol: pharmacological evidence for GABA-A receptor involvement

Analgesic effects of systemic midazolam: comparison with intrathecal administration

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