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Biomedical subjects

H J McQuay

Publications and source records attributed to H J McQuay.

At least 19 recordsLinked to original sources
PubMed1992

Morphine responsiveness of chronic pain: double-blind randomised crossover study with patient-controlled analgesia.

There is controversy about whether the lack of response of some chronic pain to opioid treatment is absolute or relative. It is widely believed that nociceptive pain is responsive to opioids whereas neuropathic pain tends not to be. We have used a method of patient-controlled analgesia (PCA) with simultaneous nurse-observer measurement of analgesia, mood, and adverse effects to address these issues. Ten patients with chronic pain were given morphine at two concentrations (10 and 30 mg/ml) by PCA in two separate sessions in a double-blind randomised crossover study. Before the study a clinical judgment was made as to whether each pain was nociceptive or neuropathic. Seven patients showed good analgesic responses (more than 70 mm pain relief on a visual-analogue scale) of pain at rest, two patients poor responses (less than 30 mm pain relief), and one a moderate response with both concentrations (30-70 mm pain relief). The response to morphine was consistent (greater and faster relief with the higher concentration) in nine patients. Two patients had pain on movement that responded moderately to low-concentration morphine and well to the higher concentration. All patients with pains judged to be nociceptive showed good analgesic responses compared with half of those with neuropathic pain. There was no evidence that analgesic responses in patients with neuropathic pain were due to changes in mood. This PCA method is a quick and efficient tool to determine the consistency of the analgesic response. Such consistency can guide the clinician as to whether continued or higher-dose opioid treatment will produce good analgesia. An inconsistent response points to the use of other pain-relieving strategies.

Adult↗
PubMed1992

Spinal antinociception by Tyr-D-Ser(otbu)-Gly-Phe-Leu-Thr, a selective delta-opioid receptor agonist.

The spinal antinociceptive potency of the delta-opioid receptor agonist, Tyr-D-Ser(otbu)-Gly-Phe-Leu-Thr (DSTBULET), was studied in rats. The tail flick test was used as nociceptive stimulus and the rotarod test was used to detect any motor or sedative effects. A dose-response curve was also made for the mu-opioid receptor agonist, morphine. The ED50 for DSTBULET was 0.3 micrograms (0.4 nmol) and a near 100% maximum effect was achieved with 5 micrograms (7.5 nmol). No motor or sedative effects were detected. Antinociception by DSTBULET was antagonized by s.c. naltrindole (1 mg/kg), a selective delta-opioid receptor antagonist, and naloxone (1 mg/kg), a non-selective opioid receptor antagonist. The ED50 for morphine was 0.5 micrograms (1.0 nmol) and the antinociceptive effects were not antagonized by naltrindole (1 mg/kg). The results evidence further the important role of the delta-opioid receptor in spinal nociceptive processing.

Amino Acid Sequence↗
PubMed1992

Evidence for the involvement of the mu but not delta opioid receptor subtype in the synergistic interaction between opioid and alpha 2 adrenergic antinociception in the rat spinal cord.

The interaction between the spinal antinociceptive effects of selective mu or delta opioid agonists morphine and DSTBULET (Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr), respectively, and the selective alpha 2 adrenergic agonist dexmedetomidine was examined on convergent dorsal horn neuronal responses in the intact anaesthetized rat. The coadministration of intrathecal morphine (0.5 microgram, 2.5 micrograms) and dexmedetomidine (0.5 microgram) produced a greater than additive inhibition of C fibre-evoked responses. Inhibitions were reversed by either the opioid antagonist naloxone or the alpha 2 adrenergic antagonist atipamezole. The coadministration of intrathecal DSTBULET (1 microgram, 2.5 micrograms) and dexmedetomidine did not result in a supra-additive inhibition of C fibre-evoked responses. The results suggest that mu rather than delta opioid receptors are involved in the synergism of spinal opioid and alpha 2 adrenergic antinociception.

Adrenergic alpha-Agonists↗
PubMed1992

The antinociceptive actions of dexmedetomidine on dorsal horn neuronal responses in the anaesthetized rat.

The actions of the selective alpha 2-adrenoceptor agonist dexmedetomidine were examined on the nociceptive C and innocuous A beta fibre-evoked responses of dorsal horn neurones to transcutaneous electrical stimulation in the intact anaesthetized rat. C fibre-evoked responses were dose dependently reduced by intrathecal dexmedetomidine--to a maximum 86 +/- 6% inhibition by 10 micrograms of the agonist. The ED50 for inhibition of C fibre responses was estimated to be 2.5 micrograms. A beta-evoked responses were inhibited to a lesser degree--a maximum 54 +/- 8% inhibition after 10 micrograms dexmedetomidine. The antinociceptive effects of dexmedetomidine were reversed by the alpha 2-adrenoceptor antagonist atipamezole and the opioid antagonist naloxone. The results are discussed with reference to adrenergic and opioid mechanisms in the spinal cord.

Action Potentials↗
PubMed1992

Low dose amitriptyline in the treatment of chronic pain.

The analgesic efficacy of amitriptyline 25 mg was compared with placebo in 41 patients with chronic (more than 3 months) nonmalignant pain, using a double-blind randomised multiple-dose 3-week treatment period crossover design. Amitriptyline 25 mg provided significantly greater efficacy than placebo, with significant differences evident within the first week. There was no significant difference on mood scores between amitriptyline and placebo. The results suggest that surprisingly low doses of amitriptyline may be effective without substantial adverse effects, that the effect is evident early, and that the effect is distinguishable from any effect of the amitriptyline on mood.

Adult↗
PubMed1992

A multiple dose comparison of combinations of ibuprofen and codeine and paracetamol, codeine and caffeine after third molar surgery.

In a randomised, double-blind, double-dummy, multiple dose, crossover study in 30 patients we compared an ibuprofen/codeine combination (400 mg ibuprofen/25.6 mg codeine phosphate) with a paracetamol/codeine/caffeine combination (1 g paracetamol/16 mg codeine phosphate/60 mg caffeine) for pain relief over 6 days after two-stage bilateral lower third molar removal. The ibuprofen combination produced significantly greater analgesia than the paracetamol combination, both on single-dose analysis of the first and second days and on multiple-dose measures for days 1, 2, 3 and 4. The mean incidence of adverse effects over the 6 days was 20% for both combinations. This trial design (crossover with multiple dosing in outpatients) is a sensitive way of testing for analgesia, and is potentially more predictive of adverse effect problems than single-dose studies. It confirms that multiple dosing may show increased efficacy.

Acetaminophen↗
PubMed1992

Opioid sensitivity of chronic pain: a patient-controlled analgesia method.

Twenty-two patients with chronic pain of malignant or nonmalignant origin were given intravenous morphine by patient-controlled analgesia. A prestudy judgment was made from the characteristics of the pain as to whether it was nociceptive or neuropathic. Analgesic efficacy was assessed by a nurse-observer; adverse events were noted and plasma morphine and metabolitie concentrations measured. Three categories of opioid response were distinguished. Good responders obtained > 70 mm relief on the visual analogue scale, with minimal or manageable adverse events. Moderate responders obtained < 70 but > 30 mm relief with more problematic adverse events, and poor responders had < 30 mm relief with troublesome adverse events. This method for the study of opioid sensitivity allowed a wide dosage range to be studied. The simultaneous analgesic and adverse event measurements showed that the spectrum of observed response was wide, and response category could be judged for the majority by 4 h. In those with poor or moderate response, adverse event severity limited further dose increment. The relationship between pain characteristics and response showed that some pains judged to be neuropathic had a good response to opioid (5/13), and some pains judged to be nociceptive did not (5/14). The study suggests that the pattern of response is not as black and white as the prediction of good response from nociceptive pain and poor from neuropathic pain would suggest, although nociceptive pain was more likely than neuropathic pain to show a good response. For the moderate responders opioid titration may, in the absence of other effective treatments, be useful, but the analgesic endpoint may not be totally satisfactory. The method provides an operational definition of opioid sensitivity.

Adult↗
PubMed1991

FLFQPQRF-amide modulates alpha 2-adrenergic antinociception in the rat dorsal horn in vivo.

The interaction between FLFQPQRFamide and alpha 2-adrenergic spinal antinociception was examined in an electrophysiological study in the intact anaesthetised rat. The inhibition of C fibre-evoked neuronal responses by the selective alpha 2-adrenergic agonist dexmedetomidine was significantly reduced by intrathecal FLFQPQRFamide pretreatment. The results suggest a modulatory role of FLFQPQRFamide in spinal alpha 2-adrenergic antinociception.

Adrenergic alpha-Agonists↗
PubMed1991

Dextromethorphan and levorphanol on dorsal horn nociceptive neurones in the rat.

Intrathecal administration of dextromethorphan and levorphanol and intravenous injection of dextromethorphan were tested on the electrophysiological response of deep multireceptive dorsal horn neurones to peripheral stimuli. Both blockade of C-fibre input to the cells and wind-up, the increase in C-fibre firing with repeated stimulus, were recorded. Intrathecal injection of levorphanol (0.25-100 micrograms) had a typical opioid effect, blocking the C-fibre input. Its affect on wind-up was dose-dependent, paralleled precisely the blocking effect on the C-fibre input and both effects were reversed by naloxone. Unlike levorphanol and other opiates, intrathecal administration of dextromethorphan (50-500 micrograms) blocked the C-fibre input and A beta response in parallel and was not reversed by naloxone. Wind-up was reduced by a maximum of 56% at the largest dose tested. Intravenous injection of dextromethorphan (5 mg/kg) also produced a reduction in wind-up but not in the C-fibre response.

Animals↗
PubMed1991

Opioid clinical pharmacology and routes of administration.

Opiate prescription is based on titration to effect. This principle is supported by the difference between the laboratory and clinical pharmacologies of opiates. Clinically the presence of nociceptive pain appears to act as a counter to the respiratory depressant effect of opiates, and perhaps the dependence, which are such features in the laboratory. Factors in choosing between opiates are described; these include onset speed, duration of effect, toxic and active metabolites and specific side-effects. Side-effect comparison between opiates is only satisfactory when the drugs are compared at equianalgesic doses. The kinetic and clinical logic of alternative routes is explored. Overall there is probably more difference between the effect of the same opiate given by different routes than between the effects of different opiates given by the same route.

Humans↗
PubMed1991

Double-blind testing fails to confirm analgesic response to extradural morphine.

We report two patients with chronic non-malignant pain in whom morphine given intravenously via a patient-controlled analgesia system produced partial pain relief but was accompanied by severe side effects. Open administration of epidural morphine resulted in complete pain relief with minimal side effects and the patients were considered as candidates for implanted opioid delivery systems. However, when the epidural morphine was given in a double-blind and placebo-controlled manner, morphine did not produce greater analgesia than placebo and no dose-response relationship was seen. These cases show that careful investigation is necessary before proceeding to implanted systems and that changing the route did not improve the analgesia:side effect balance for morphine in these patients.

Adult↗
PubMed1990

Benzydamine cream for the treatment of post-herpetic neuralgia: minimum duration of treatment periods in a cross-over trial.

In a double-blind multiple-dose cross-over study benzydamine 3% cream was compared with placebo for the treatment of post-herpetic neuralgia. Pain relief, pain intensity, sleep, escape analgesic consumption and side effects were assessed by diary methods for the 2 week treatment periods, with 1 week run-in and 1 week wash-out. There were no significant differences between the 2 treatments. The implications of the results for other antiprostaglandin remedies recommended for treatment of post-herpetic neuralgia are discussed. An important observation with methodological significance for similar studies of chronic conditions was that short treatment periods may produce false positive results. Patients' expectations are high, and if the first study treatment is ineffective, initial significant benefit may be noted when crossing over to the next treatment; this may not last longer than 1 week. Cross-over studies in which neither treatment is effective may, therefore, produce erroneous results if treatment periods are shorter than 2 weeks.

Administration, Topical↗
PubMed1990

Intrathecal etorphine, fentanyl and buprenorphine on spinal nociceptive neurones in the rat.

Single unit recordings were made in the lumbar dorsal horn in the intact anaesthetized rat from convergent, multireceptive neurones. Activity was evoked by A beta and C fibre transcutaneous electrical stimulation of hind paw receptive fields. Three opioids, fentanyl, etorphine and buprenorphine were applied either intrathecally or intravenously and their effects on neuronal responses were examined. Intrathecal fentanyl and etorphine produced clear selective naloxone-reversible inhibitions of C fibre-evoked responses (ED50 = 24 micrograms and 0.6 micrograms respectively). Fentanyl, a mu opioid receptor agonist, was more potent at a given dose when given systemically, but etorphine, a non-selective opioid agonist, was similarly potent by both routes. In contrast to fentanyl and etorphine, intrathecal buprenorphine produced facilitations of C fibre-evoked responses at a low dose (15 micrograms), but inhibited both C and A beta fibre-evoked responses equally at a higher dose (125 micrograms). Inhibitions were found to be irreversible by naloxone. No inhibition of either C or A beta responses occurred following intravenous buprenorphine (10-1070 micrograms). The results are discussed in the light of the relationships between lipophilicity, opioid receptor selectivity and potency for spinally applied opioids.

Animals↗
PubMed1990

Bromfenac, acetaminophen, and placebo in orthopedic postoperative pain.

In a double-blind, placebo-controlled, single-dose, parallel-group study, oral doses (5, 10 and 25 mg) of the prostaglandin synthetase inhibitor bromfenac were compared with acetaminophen (1000 mg) and placebo for postoperative orthopedic pain. Analgesic measurements were made by nurse observers by use of standard verbal rating and visual analog scales. For most pain intensity and pain relief measurements, 1000 mg acetaminophen was statistically superior to placebo, demonstrating assay sensitivity, and 10 and 25 mg doses of bromfenac were statistically better than both placebo and 5 mg bromfenac for ordinal and analog ratings of pain intensity and pain relief; 25 mg bromfenac produced significantly longer time to remedication than acetaminophen. The 5 mg dose of bromfenac was statistically superior to placebo for some measures, including remedication time. There were no untoward adverse effects or alterations in vital signs. Overall, 10 mg bromfenac produced analgesia equivalent to that of 1000 mg acetaminophen in this pain context.

Acetaminophen↗