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Biomedical subjects

J H Liles

Publications and source records attributed to J H Liles.

8 recordsLinked to original sources

The effects of buprenorphine, nalbuphine and butorphanol alone or following halothane anaesthesia on food and water consumption and locomotor movement in rats.

Locomotor activity and food and water consumption are potentially indices of post-operative pain in laboratory rodents, but it is important to establish whether these variables are directly affected by opioid analgesics or by halothane anaesthesia in normal rats. The effects of three opioids, buprenorphine, nalbuphine and butorphanol administered alone or following halothane anaesthesia, were studied in groups of normal non-operated adult Wistar rats. All 3 analgesics affected food intake and activity levels, but had little or no effect on water intake. Buprenorphine caused a significant elevation of activity levels and a reduction in food intake at clinical doses (0.01 and 0.05 mg/kg s/c). Nalbuphine (0.5, 1 and 2 mg/kg s/c) caused a reduction in food intake but had a smaller stimulatory effect on locomotion. Butorphanol (0.4 mg/kg s/c) caused a reduction in food intake and elevation in activity. These results suggest that water consumption is likely to be a more reliable variable to use when assessing post-operative pain and the efficacy of analgesics in rats.

Anesthesia

The use of non-steroidal anti-inflammatory drugs for the relief of pain in laboratory rodents and rabbits.

The data concerning the use of non-steroidal anti-inflammatory drugs (NSAIDs) and evidence for their efficacy in laboratory rats and mice are reviewed. This information is then extrapolated to clinical situations and dose rates that take account of ulcerogenic side effects are recommended. NSAIDs have the potential to be a very useful group of analgesics and should always be considered when attempting to provide pain relief in laboratory animals.

Analgesia

Fentanyl and medetomidine anaesthesia in the rat and its reversal using atipamazole and either nalbuphine or butorphanol.

The intraperitoneal injection of anaesthetic agents is a simple and convenient method of anaesthetizing rats. However, all of the anaesthetic combinations in current use which are administered by intraperitoneal injection produce prolonged sedation, and full recovery of consciousness may take several hours. Fentanyl, a mu agonist opioid, and medetomidine, an alpha 2-adrenoceptor agonist were mixed and administered as a single intraperitoneal injection. Combinations of 300 micrograms/300 micrograms/kg and 300 micrograms/200 micrograms/kg of fentanyl/medetomidine were shown to produce surgical anaesthesia in the rat. This anaesthetic regimen produced significant respiratory depression (P less than 0.01) and animals did not regain their righting reflex until 193 +/- 21 min (mean +/- 1 SD) after injection. Administration by intraperitoneal injection of atipamezole, a specific alpha 2-adrenoceptor antagonist (1 mg/kg) mixed with a mu antagonist/k agonist opioid (nalbuphine, 2 mg/kg or butorphanol 0.4 mg/kg), resulted in a rapid (less than 8 min) reversal of anaesthesia and the associated respiratory depression, and apparent full recovery of consciousness.

Anesthesia

The effects of surgical procedures, halothane anaesthesia and nalbuphine on locomotor activity and food and water consumption in rats.

A study was undertaken to investigate the effects of surgical procedures on food and water intake and spontaneous locomotor activity in laboratory rats. The influence of anaesthesia with halothane and administration of the opioid analgesic nalbuphine was investigated in normal rats and in animals which underwent either unilateral nephrectomy or jugular vein cannulation. Both nephrectomy and jugular cannulation were associated with a significant reduction in food and water consumption and a depression in locomotor activity levels. The reduction in activity following nephrectomy was reversed by administration of 6 doses of nalbuphine at 4 hourly intervals. Administration of nalbuphine at the same dose rate following halothane anaesthesia in normal rats resulted in a stimulation of activity. The prevention of the depressant effects of surgery by this opioid appears to be due to its stimulatory effect rather than a specific analgesic action. The degree of depression of food and water consumption after nephrectomy was significantly reduced following 6 doses of nalbuphine. This beneficial effect of repeated administration of an opioid may be related to the compound's analgesic action.

Animals

Post-operative analgesia following thoracotomy in the dog: an evaluation of the effects of bupivacaine intercostal nerve block and nalbuphine on respiratory function.

Pain following thoracotomy reduces pulmonary ventilation in man and a similar effect is believed to occur in animals. The effects of two analgesic regimens on arterial blood gas parameters were studied in dogs following thoracotomy. Post-Operative analgesia was provided with intermittent nalbuphine, either alone or in combination with an intercostal nerve block using bupivacaine. Arterial blood gas analysis was carried out at 4, 8 and 16 h post-operatively, both before the administration of nalbuphine and again 30 min later. Animals which received nalbuphine alone had a significant rise in arterial oxygenation following administration of this analgesic. This effect was not observed at 4 and 8 h post-operatively in dogs which had an intercostal block with bupivacaine, but was seen at 16 h post-operatively when it could be anticipated that the effects of bupivacaine would have waned. These results suggest that intercostal block with bupivacaine can provide analgesia for over 8 h, and that the duration of action of nalbuphine in controlling post-operative pain in the dog is probably less than 4 h.

Animals

The use of lignocaine-prilocaine local anaesthetic cream for pain-free venepuncture in laboratory animals.

An assessment was made of the effects of topical application of a eutectic mixture of local anaesthetics (EMLA cream) in a number of species of laboratory animals. Application of EMLA cream enabled percutaneous insertion of catheters into the cephalic vein in dogs and cats and the marginal ear vein in rabbits without causing any detectable pain or discomfort. Application to the tail in rats prior to percutaneous cannulation of the lateral tail vein did not produce a significant reduction in the behavioural responses to venepuncture. EMLA cream represents a useful refinement of current techniques for intravenous injection in some species, and is especially valuable when the procedure is to be undertaken by an inexperienced operator.

Anesthetics, Local

Reversal of fentanyl/fluanisone neuroleptanalgesia in the rabbit using mixed agonist/antagonist opioids.

The reversal of the neuroleptanalgesic combination of fentanyl/fluanisone using mixed agonist/antagonist opioids has been investigated in the rabbit. All of the compounds studied (naloxone, nalbuphine, meptazinol, butorphanol, buprenorphine, pentazocine, doxapram) reversed the respiratory depression and sedation produced by fentanyl/fluanisone. Fentanyl/fluanisone produced profound analgesia for 180 min, which was rapidly and completely antagonized by naloxone. The mixed agonist/antagonist opioids produced a reduction in the degree of analgesia but, in contrast to naloxone, analgesic activity persisted from 120 min (meptazinol) to 420 min (buprenorphine). Administration of buprenorphine to rabbits anaesthetized with fentanyl/fluanisone and midazolam confirmed that the reversal of respiratory depression was accompanied by the return of arterial pH, PCO2 and PCO2 to preanaesthetic values. The use of neuroleptanalgesic anaesthetic regimens, which have been shown to provide effective surgical anaesthesia, combined with reversal using a mixed agonist/antagonist opioid to provide postoperative analgesia, appears to be a valuable refinement of current laboratory animal anaesthetic practice.

Analgesics