Canadian Journal of Anesthesia

, Volume 53, Issue 10, pp 1004–1009 | Cite as

Analgesic effects of systemic midazolam: comparison with intrathecal administration

  • Tomoki NishiyamaEmail author
Regional Anesthesia and Pain



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.


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 tosc hind paw formalin injection were compared following intrathecal injection of midazolam (1, 3, 10, 30, or 100 μg in 10μL) orip 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.


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.


Systemically administered midazolam induced antinociception for inflammatory pain only, while intrathecal administration elicited antinociceptive effects on both acute thermal and inflammatory-induced pain.


Midazolam Antinociceptive Effect Formalin Test Intrathecal Administration Tail Flick 
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Les effets analgésiques du midazolam à action générale: comparaison avec l’administration intrathécale



Administré par voie intrathécale, le midazolam a des effets antinociceptifs, mais les effets d’une administration intra-péritonéale(ip) demeurent controversés. Dans la présente étude, nous avons vérifié les propriétés antinociceptives de l’administration générale vs intrathécale du midazolam chez un modèle expérimental de douleur thermique et inflammatoire chez le rat.


Un cathéter intrathécal lombaire a été mis en place chez 176 (n = 8 animaux par dose croissante) rats mâles Sprague-Dawley. 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 (1, 3, 10, 30, or 100 μg dans 10 μL) ou l’administration ip (3, 30, 300, ou 3 000 μg dans 300 μL). Une solution salée, 10 μL ou 300 μL, a servi de solution témoin. Les effets secondaires comportementaux et les troubles moteurs ont été aussi examinés.


L’administration intrathécale de midazolam a augmenté la latence de la rétraction de la queue en fonction de la dose (P < 0,05) avec une dose efficace moyenne (ED50) de 1,60μg, tandis que l’administration ip n’a pas augmenté la latence. Les voies d’administration intrathécale et ip ont réduit le nombre de retraits de la patte au cours des phases 1 et 2 du test à la formaline (P < 0,05). Les ED50 ont été de 1,26 μg [intervalle de confiance (IC), 0,35–3,18 μg], (phase 1) et de 1,20μg (IC, 0,29–3,71 μg), (phase 2) avec l’administration intrathécale et de 11,6 μg (IC, 2,5–19,3 μg), (phase 1) et de 52,2 μg (IC, 18,3–102,7 μg), (phase 2) avec l’administration ip.


L’administration intrapéritonéale de midazolam a induit une antinociception pour la douleur inflammatoire seulement alors que l’administration intrathécale a produit des effets antinociceptifs sur la douleur thermique aiguë et la douleur induite par l’inflammation.


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© Canadian Anesthesiologists 2006

Authors and Affiliations

  1. 1.Department of AnesthesiologyThe University of Tokyo, Faculty of MedicineTokyoJapan

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