Modulation of the gait deficit in arthritic rats by infusions of muscimol and bicuculline.

Gait analysis in the adjuvant-induced arthritic rat model of chronic pain was used to examine the role of GABA(A) receptors in the development of pain. Drug solutions were administered continuously at 5+/-0.75 microl/h for 14 days via Alzet osmotic pumps (2ML2) placed under the skin of the back.

Gait analysis as a correlate of pain induced by carrageenan intraplantar injection.

The aim of this study was to investigate whether gait changes occurring during the development of carrageenan induced rodent paw inflammation could be measured to provide an objective marker of persistent pain. The objectives were to measure hind limb tibiotarsal joint diameter as an indication of inflammatory oedema and to analyse gait during the development of the carrageenan induced persistent pain. Rear paw intraplantar injection of 6 mg (150 microl) lambda-carrageenan resulted in significant swelling of rear limbs at 90 min (P=0.

Gait analysis as an objective measure in a chronic pain model.

The aim of this study was to investigate objective characterisation of gait as a marker of the chronic pain of adjuvant arthritis (AA). Video recorded images of spontaneous rat ambulations were analysed to quantify various temporal and spatial parameters and compare these between the AA and control groups. Changes were also recorded after the administration of a single dose of buprenorphine (15 ?g).

Treatment of postoperative pain in oral and maxillofacial surgery.

We questioned 75 patients after inpatient oral and maxillofacial operations to find out how satisfied they were with the extent to which their pain had been controlled. Seventy (93%) had had postoperative pain. In 33 (47%), it was moderate and in 24 (34%), severe.

Behavioural measurement of postoperative pain after oral surgery.

The amount and type of postoperative analgesia prescribed depends on the clinician's judgement of the patient's need. Among other factors, this judgement is likely to be based on the patient's behaviour. The primary aim of this study was to investigate the validity of using behavioural measures to provide information about a patient's experience of pain during the early stages of recovery from oral surgery under general anaesthesia.

Biochemical aspects of chronic pain and its relationship to treatment.

This review presents an overview of the neurotransmitters and neuromodulators involved in acute and chronic pain. Although there is little evidence that the neuronal pathways differ in the two types of pain, it is clear that different transmitters or receptor types are involved in hyperalgesia and chronic pain. While most attention has been focussed on spinal processes, it is apparent that some types of chronic pain have both a peripheral and a supraspinal component.

Interactions between opioid drugs and propofol in laboratory models of seizures.

Propofol (i.v. and i.

Interactions involving new antiepileptic drugs.

The advent of new antiepileptic drugs (AED) has increased the opportunities for interaction. Clinicians seek therapeutic interactions in which two AED together have greater efficacy than either drug alone; there are case reports of such, but few prospective studies. Interactions must also be suspected when the adverse effects of a new AED differ according to the co-medication.

The activity of opioid analgesics in seizure models utilizing N-methyl-DL-aspartic acid, kainic acid, bicuculline and pentylenetetrazole.

Morphine, fentanyl and pethidine exhibited a biphasic dose response relationship with respect to their effects on seizure thresholds to bicuculline, pentylenetetrazole, N-methyl-DL-aspartate (NMDLA) and kainic acid in mice. The usual pattern was for low doses to be anticonvulsant and higher doses to be proconvulsant. However this pattern was reversed for fentanyl and pethidine when NMDLA was used to induce seizures.

Protective effect of flunarizine and nifedipine alone and in combination with anticonvulsant drugs against PTZ-induced seizures in mice.

The anticonvulsant effect of flunarizine has been compared to that of nifedipine in the pentylenetetrazole (PTZ)-induced seizure incidence/latency test and the PTZ seizure threshold test in mice. Nifedipine was found to have anticonvulsant activity in both models but flunarizine only had an anticonvulsant effect in the PTZ seizure incidence/latency test. Interactions with commonly used anti-epileptic drugs were also examined.

Impairment of psychomotor function at modest plasma concentrations of carbamazepine after administration of the liquid suspension to naive subjects.

1. The influence of pharmaceutical formulation on the plasma drug concentration-time curve and the psychomotor responses to 400 mg carbamazepine has been assessed in 12 healthy male volunteers; three formulations and placebo were compared in a randomised, blind, crossover study. 2.

Opioid receptors and awareness of the Greek alphabet.

Several years ago a colleague, John Hugh Rees, set the following question for a final BSc Pharmacology exam: 'Describe current views about the classification of opioid receptors. Is the classification you describe of much relevance or has it merely served to make you more aware of the Greek alphabet?' This question is still relevant today.

Tolerance to the anticonvulsant effects of clobazam in mice.

Tolerance to the anticonvulsant effects of clobazam has been studied in three murine models of epilepsy: pentylenetetrazole- and N-methyl-D,L-aspartic acid-induced seizures and audiogenic-induced seizures in the DBA/2 strain. Tolerance occurred most rapidly in the pentylenetetrazole model but the development of tolerance could be reduced by increasing the dose interval. Tolerance to the protective effects of clobazam occurred more readily to the first tonic seizure than to the full tonic clonic seizure.

Modification by drugs used in anaesthesia of CNS stimulation induced in mice by laudanosine and strychnine.

We have investigated in mice the effects of several drugs which may be administered as part of an anaesthetic technique on the convulsive threshold to laudanosine and to strychnine, which is reported to have a similar mechanism of action. I.v.

Relationship between analgesia and respiratory depression for mu opioid receptor agonists in mice.

The relationship between analgesic activity, measured as the hot plate reaction time, and respiratory depression, measured as ventilatory frequency, was investigated in mice for a variety of mu opioid receptor agonists with differing selectivities for mu receptors compared with delta receptors. There was a weak correlation between analgesia and respiratory depression for opioids with the greatest selectivity for mu opioid receptors compared with delta receptors, such as alfentanil. The strength of the correlation increased for opioids which had greater delta receptor activity, such as morphine and fentanyl.

Respiratory and sedative effects of clobazam and clonazepam in volunteers.

1. The respiratory and psychomotor effects of two benzodiazepines used mainly as anticonvulsants were compared in healthy volunteers, using a double-blind placebo controlled design. 2.

An in-vitro study of the interactions between intravenous induction agents and the calcium antagonists verapamil and nifedipine.

Thiopentone, propofol and etomidate inhibit the contractions of the rat isolated atria and portal vein. The actions of thiopentone and propofol summate with those of verapamil and nifedipine. Verapamil potentiates the action of etomidate on both preparations.

Doxapram and the neuromuscular junction.

We have studied the action of doxapram on neuromuscular transmission in the rat phrenic nerve-diaphragm preparation. Doxapram augmented neuromuscular transmission in a dose-related manner when a threshold concentration of 5 x 10(-5) mol litre-1 had been exceeded. The activity of the acetylcholinesterase in rat diaphragm has been examined also in the presence of doxapram.

Effect of oral doxapram on morphine-induced changes in the ventilatory response to carbon dioxide.

A double-blind crossover volunteer trial has been carried out to determine if oral doxapram reduces the respiratory depression caused by morphine 0.12 mg kg-1 i.m.

Stimulant action of pethidine on the pregnant rat uterus in-vitro.

Pethidine's stimulant action on the 22-day pregnant rat isolated uterus does not involve receptors sensitive to methysergide and is unlikely to involve the synthesis and release of endogenous prostaglandins. The sensitivity of pethidine-induced contractions to verapamil suggests that mobilization of extracellular calcium is necessary for pethidine's action.

The effect of meptazinol on the guinea-pig sphincter of Oddi in-vitro.

Meptazinol causes a dose-dependent contraction of the guinea-pig sphincter of Oddi in-vitro. This was antagonized by atropine in concentrations which blocked the contractile response to acetylcholine but not that to KCl. Naloxone was unable to block the response of the tissue to meptazinol, and other opioid drugs had inconsistent effects.

The respiratory effects of oral ethyl loflazepate in volunteers.

A volunteer study was undertaken to assess the respiratory effects of ethyl loflazepate, a new benzodiazepine, and to correlate these with plasma concentrations of the active metabolites. Twelve volunteers were given placebo, 2 mg ethyl loflazepate, and 6 mg ethyl loflazepate on separate occasions. Respiration and plasma metabolite levels were assessed hourly for 8 h and at 24 h.