Analgesic effects of systemic midazolam: comparison with intrathecal administration

Nishiyama, Tomoki

doi:10.1007/bf03022529

Cited by 24 publications

(25 citation statements)

References 20 publications

(37 reference statements)

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“…Although midazolam produces antinociceptive effects when co-administered with morphine intrathecally through the action on GABA-A receptors [17], it may also have inhibitory effects on opioid analgesia at the supraspinal level through the inhibition of the pain-inhibitory system. Moreover, midazolam may also evoke hyperalgesia and its analgesic effects may be influenced by rat strains [18]. Therefore, these factors may have contributed to the lack of morphine analgesia enhancement after co-administration with midazolam in our study.…”

Section: Discussionmentioning

confidence: 66%

Analgesic Effects of Morphine in Combination with Adjuvant Drugs in Rats

Leppert¹,

Okulicz-Kozaryn

Kamińska

et al. 2014

Pharmacology

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Background: Morphine is co-administered with adjuvant drugs to treat pain, nausea, vomiting, dyspnoea and delirium in cancer patients. Aim of the Study: To investigate analgesic effects of morphine when co-administered with adjuvant drugs. Material and Methods: Two-month-old male Wistar rats received single morphine doses alone (0.45 and 0.9 mg/kg) or with midazolam (0.3 mg/kg), haloperidol (0.15 and 0.45 mg/kg), levomepromazine (0.35 mg/kg), metoclopramide (1.0 mg/kg), and hyoscine butylbromide (1.7 mg/kg) as single subcutaneous injections. Analgesia was measured by the tail-flick test after 15, 30, 45, 60, and 90 min of drug administration. In the case of significant analgesia enhancement, analgesic and sedative effects were explored in 3-, 5-, 6-, 8-, and 11-month-old rats. Results: Significant morphine (0.9 mg/kg) analgesia enhancement was observed 60 min after haloperidol (0.15 and 0.45 mg/kg) and hyoscine butylbromide co-administration. The addition of haloperidol to morphine significantly increased analgesia in 6-, 8- and 11-month-old rats while in the case of hyoscine butylbromide co-administration this effect was observed only in 11-month-old rats. Conclusions: Haloperidol and hyoscine butylbromide enhanced morphine analgesia. Future studies may explore the repeated administration of these drug combinations in rats and humans. i 2014 S. Karger AG, Basel

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Section: Discussionmentioning

confidence: 66%

Analgesic Effects of Morphine in Combination with Adjuvant Drugs in Rats

Leppert¹,

Okulicz-Kozaryn

Kamińska

et al. 2014

Pharmacology

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“…MID may also evoke hyperalgesia and its analgesic effects may be influenced by rats' races [32]. MET is suggested to potentiate opioid analgesia [33] through the interaction with opioid receptors [34] and other putative mechanisms [35], although experimental [36] and clinical data did not confirm these observations [37].…”

Section: Research Wojciech Leppertmentioning

confidence: 63%

Analgesic and Anti–Inflammatory Effects of Oxycodone with Adjuvant Drugs in an Experimental Study of Nociceptive and Neuropathic Pain

Leppert¹,

Szulc²,

Kaczmarek³

et al. 2018

Neuropsychiatry

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Objective: Opioids are often combined with adjuvants to treat symptoms that accompany pain and with adjuvant analgesics to treat neuropathic pain. Herein, we aim to investigate the analgesic and anti-inflammatory effects of oxycodone and selected adjuvants in rats.Methods: Analgesic and anti-inflammatory effects of oxycodone were assessed after single subcutaneous (SC) (0.56 mg/kg) injections in rats, with the following drugs: midazolam (0.3 mg/kg), haloperidol (0.45 mg/kg), ketamine (0.3 mg/kg), hyoscine butylbromide (1.7 mg/kg), levomepromazine (0.35 mg/kg), and metoclopramide (1.0 mg/kg). Analgesia was assessed by the tail flick test. Anti-inflammatory activity was evaluated using a plethysmometer after carrageenan-induced edema. For neuropathic pain, analgesia was explored using the tail flick and von Frey tests. Neuropathic pain was induced by vincristine (0.1 mg/kg, i.p.) in male Wistar rats.Results: All tested combinations of oxycodone with particular adjuvants showed increased analgesia in comparison to oxycodone alone. Compared to oxycodone alone, combinations with midazolam, haloperidol, hyoscine butylbromide, and levomepromazine prolonged analgesia. Anti-inflammatory activities were observed after coadministration of oxycodone paired with haloperidol and ketamine, which is a new aspect of the pharmacological profile of oxycodone. In the neuropathic pain model, vincristine lowered pain threshold in rats and inhibited growth of normal rat body weight. Oxycodone in combination with adjuvant analgesics showed more potent analgesia than oxycodone alone, especially in the tail-flick test. In most cases, the maximum effects were observed for 15-30 min since combined SC administration.Conclusions: Analgesic and anti-inflammatory effects were observed in oxycodone combined with selected adjuvants in rats; although the mechanism of these interactions is not yet well understood. Further studies should test these combinations after chronic administration and assess the benefits and risks associated with the use of the tested combinations in humans.

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“…It has further been argued that intrathecal midazolam reduces excitatory GABA-mediated neurotransmission in interneurons, leading to a decrease in the excitability of spinal dorsal horn neurons (19). In animal studies, research has shown that intrathecal midazolam increases the pain threshold by binding to benzodiazepine receptors in the spinal cord (20)(21)(22)(23). One study (24) reported that when 2 mg intrathecal midazolam were added to 1.5 mL of 5% lignocaine in women who underwent a caesarean section delivery, postoperative pain relief was evident.…”

Section: Discussionmentioning

confidence: 99%