naloxone and Ischemia

In the runner study, as measured by tourniquet ischemic pain, exercise stress produced hypoalgesia 20 minutes post-run, followed by hyperalgesia and euphoria at 30 minutes. The hypoalgesia and euphoria were reversed by naloxone. Exercise stress also produced a decrease in P(A), suggesting hypoalgesia to the thermal cutaneous stimulation. However, this analgesia was not naloxone reversible. Nor did exercise stress produce analgesia to cold-pressor pain. In the acupuncture study, noxious electrical stimulation of classical acupuncture sites failed to produce analgesia either during or after stimulation. However, expectation did produce a change in the pain report criterion, but only in the acupunctured arm. Noxious electrical stimulation (TENS) of the median nerve produced no analgesia outside of the related segmental area, that is, acute electrical pain did not produce generalized hypoalgesia. Thus, the effects of the stress produced by noxious electrical stimulation differ from that produced by exercise. In contrast to the results of the acute pain studies, chronic clinical pain, which combines mental stress and pain stress, produced strong hypoalgesia and anesthesia. Again, in contrast to the acute experimental pain studies, the emotional stress of mental illness produces hypoalgesia, but not anesthesia. Finally, the somatosensory system is not the only the sensory system affected by stress. Cold-pressor pain decreases visual sensitivity both during and for a few minutes following stimulation, and does not interfere with short-term (supra-digit span) memory.

Topics: Acupuncture Therapy; Acute Disease; Adult; Back Pain; Chronic Disease; Cold Temperature; Discrimination Learning; Electric Stimulation; Emotions; Female; Hormones; Hot Temperature; Humans; Ischemia; Male; Memory; Mental Disorders; Naloxone; Pain; Physical Exertion; Sensory Thresholds; Stress, Physiological; Visual Perception

Endogenous opioid peptides are released in response to stressful situations, such as circulatory shock, both as hormones and as central and peripheral neurotransmitters. Naloxone, an opiate antagonist, improves cardiovascular function in a variety of animal models of shock caused by endotoxemia, hemorrhage, anaphylaxis, or spinal trauma. Administration of thyrotropin-releasing hormone (TRH) in supraphysiologic doses also has pressor effects in these shock models. Given acutely after injury, TRH improves recovery in models of spinal trauma; however, the experimental effects of TRH do not involve action at the opiate receptor. Clinical evaluation of the use of naloxone in patients with shock has been largely limited to treatment of sepsis. The paucity of prospective, randomized trials makes these clinical data difficult to evaluate, but in septic patients the use of naloxone does not seem to improve survival. The use of naloxone in shock of other etiologies has not been clinically investigated, and may hold greater promise. Acute-phase treatment of spinal trauma victims with TRH is currently undergoing clinical trials.

Topics: Adult; Animals; Blood Pressure; Endorphins; Humans; Hypotension; Ischemia; Naloxone; Shock, Hemorrhagic; Shock, Septic; Shock, Traumatic; Thyrotropin-Releasing Hormone

Topics: Adolescent; Adult; Amenorrhea; Arthritis, Infectious; Bone Diseases; Chemical and Drug Induced Liver Injury; Coma; Endocarditis, Bacterial; Extremities; Female; Fetal Growth Retardation; Hepatitis, Viral, Human; Heroin Dependence; Humans; Infant, Newborn; Ischemia; Male; Naloxone; Neurologic Manifestations; Pregnancy; Pregnancy Complications; Respiratory Tract Diseases; Sepsis; Skin Manifestations; Tetanus

We investigated the mechanisms underlying the activation of endogenous opioids in placebo analgesia by using the model of human experimental ischemic arm pain. Different types of placebo analgesic responses were evoked by means of cognitive expectation cues, drug conditioning, or a combination of both. Drug conditioning was performed by means of either the opioid agonist morphine hydrochloride or the nonopioid ketorolac tromethamine. Expectation cues produced placebo responses that were completely blocked by the opioid antagonist naloxone. Expectation cues together with morphine conditioning produced placebo responses that were completely antagonized by naloxone. Morphine conditioning alone (without expectation cues) induced a naloxone-reversible placebo effect. By contrast, ketorolac conditioning together with expectation cues elicited a placebo effect that was blocked by naloxone only partially. Ketorolac conditioning alone produced placebo responses that were naloxone-insensitive. Therefore, we evoked different types of placebo responses that were either naloxone-reversible or partially naloxone-reversible or, otherwise, naloxone-insensitive, depending on the procedure used to evoke the placebo response. These findings show that cognitive factors and conditioning are balanced in different ways in placebo analgesia, and this balance is crucial for the activation of opioid or nonopioid systems. Expectation triggers endogenous opioids, whereas conditioning activates specific subsystems. In fact, if conditioning is performed with opioids, placebo analgesia is mediated via opioid receptors, if conditioning is performed with nonopioid drugs, other nonopioid mechanisms result to be involved.

Topics: Adult; Analgesia; Analgesics, Opioid; Conditioning, Operant; Cues; Double-Blind Method; Endorphins; Female; Humans; Ischemia; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain; Placebos

Previous studies suggested that endogenous opiates may attenuate the cardiovascular and sympathetic adjustments to static exercise. We tested whether this effect originates from exercising skeletal muscle. Eight men performed 2 min of static handgrip (30% maximum) followed by 2 min of posthandgrip muscle ischemia after three interventions: 1) control, 2) intra-arterial injection of naloxone HCl (60 micrograms) or vehicle (saline) in the exercising arm, and 3) systemic infusion of naloxone (4 mg) or vehicle. Naloxone and vehicle trials were performed double blind on separate days. Preexercise baseline muscle sympathetic nerve activity (burst frequency), heart rate, and blood pressure were similar across interventions on either day. During static handgrip, control, intra-arterial, and systemic administration of vehicle and naloxone elicited similar increases in total muscle sympathetic nerve activity (58 +/- 24 vs. 68 +/- 26, 146 +/- 49 vs. 132 +/- 42, 137 +/- 54 vs. 164 +/- 44%, respectively), heart rate (9 +/- 2 vs. 8 +/- 3, 16 +/- 3 vs. 16 +/- 2, 20 +/- 4 vs. 19 +/- 3 beats/min, respectively), and mean arterial pressure (22 +/- 4 vs. 21 +/- 4, 29 +/- 5 vs. 26 +/- 3, 28 +/- 4 vs. 27 +/- 4 mmHg, respectively). Additionally, there were no differences between vehicle and naloxone trials during posthandgrip muscle ischemia. Thus, contrary to previous reports, we conclude that the endogenous opiate peptide system does not modulate cardiovascular and sympathetic responses to brief periods of static exercise or muscle ischemia in humans.

Topics: Adolescent; Adult; Blood Pressure; Double-Blind Method; Exercise; Hand Strength; Heart Rate; Hemodynamics; Humans; Ischemia; Male; Muscle Fibers, Skeletal; Naloxone; Sympathetic Nervous System

The effect of breathing CO2 on somatic sensitivity was studied in human subjects. Healthy humans breathed room air, 100% O2, or CO2 (5% or 8% in O2). Thresholds to heat pain, mechanical pain, electrically evoked pain, and electrically evoked perception were measured using psychophysical techniques. Also, the effects on sensory and affective components of experimental ischaemic pain, alertness and on cardiovascular parameters were observed. In addition, the effect of CO2 on heat pain threshold was determined in the ischaemic limb to exclude the possibility that the threshold elevation was due to an action on primary afferent fibres. Naloxone (0.8 mg), dexamethasone (0.1 mg) or placebo (0.9% NaCl) were applied intravenously in double blind tests to reverse the threshold elevations. In an electrophysiological experiment the effect of CO2 on a spinal nociceptive flexion reflex evoked by an electric stimulus was measured. The CO2 produced a dose-dependent elevation of the heat pain threshold. Similarly, the sensory and affective components of experimental ischaemic pain were attenuated by CO2. The heat pain threshold was significantly elevated by CO2 in the ischaemic limb, also. However, there was no effect on thresholds to mechanically or electrically induced pain or perception thresholds to electrically evoked sensations. One hundred percent O, did not elevate the heat pain threshold. In double blind tests the heat pain threshold elevation was not significant when the naloxone or dexamethasone was administered. The threshold to electrically evoked spinal flexion reflex was not elevated by CO2. The CO2 at the current dose produced sedation, an increase in blood pressure but no change in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Arousal; Blood Pressure; Carbon Dioxide; Dexamethasone; Electroshock; Female; Heart Rate; Hot Temperature; Humans; Hypercapnia; Ischemia; Male; Middle Aged; Naloxone; Pain Threshold; Perception; Physical Stimulation

The analgesic efficiency of ketamine and pethidine was compared in experimental ischemic pain and postoperative pain after oral surgery. Naloxone 1.6 mg or placebo was given 5 min before the analgesic drug. The subjects recorded their pain on a visual analogue scale. Both ketamine 0.3 mg/kg and pethidine 0.7 mg/kg were effective as analgesics against the two types of pain studied. Naloxone prevented the analgesic effect of pethidine, but had no effect on ketamine analgesia. The results are in accordance with the hypothesis that the analgesic effect of ketamine is mediated by a non-opioid mechanism, possibly involving PCP-receptor-mediated blockade of the NMDA-receptor-operated ion channel.

Topics: Adult; Female; Humans; Ischemia; Ketamine; Meperidine; Naloxone; Pain; Pain, Postoperative; Visual Pathways

A double-blind randomized placebo-controlled study was carried out in 8 healthy volunteers to determine whether the analgesic and other actions of meptazinol could be reversed by naloxone or hyoscine. Heart rate, blood pressure, respiratory rate, pupil diameter, forearm ischaemic exercise tolerance and dental pain threshold were measured before and up to 45 minutes after intramuscular meptazinol 100 mg or placebo, when 'reversal' was attempted with intravenous naloxone 2 mg, hyoscine 1.6 mg or placebo. Meptazinol caused mild pupillary constriction which is unlikely to be clinically significant. Forearm ischaemic exercise tolerance failed to show any analgesic effect of meptazinol. Measurement of dental pain threshold strongly suggested reversal of meptazinol analgesia by naloxone but not by hyoscine, but inter-subject variation in analgesic response was great and these results require confirmation in a group pre-selected for consistent response.

Topics: Adult; Analgesics; Azepines; Dental Pulp; Humans; Ischemia; Male; Meptazinol; Naloxone; Pain; Physical Exertion; Sensory Thresholds; Time Factors

Fifty-two paid volunteers participated in two separate factorial investigations of the effects of naloxone on time tolerance of and affective reactions to ischemia, as a function of the interaction between expectations of involvement in the experimental situation and experimental variables involving stress or suggestions of analgesia. Naloxone-induced reduction in tolerance to ischemia interacted significantly with the level of involvement expectancies. The suggestion of analgesia provided no significant naloxone-saline discrimination, but there was a significant interaction between variable memory task conditions and drug effects on the time ischemia was tolerated. These findings suggest that naloxone-opiate receptor interactions may depend on individual differences in attitudes to the situation, but may be potentiated by select environmental stimuli. Analyses of the effects of treatment on affective reactions to ischemia failed to show consistent results.

Topics: Adult; Affect; Analgesics; Female; Humans; Individuality; Ischemia; Male; Memory; Naloxone; Stress, Physiological; Suggestion; Time Factors

The possible reversal of nitrous oxide analgesia by naloxone was investigated. Two studies were conducted in 21 healthy male subjects, who responded to ischemic pain produced by tourniquet applied to the upper arm for 15 min, while breathing air or nitrous oxide, 33 per cent. Using a double-blind procedure, the subjects received intravenous injections of naloxone and saline solution on different days. In eight subjects, naloxone, 8 mg, administered without nitrous oxide, had no effect on pain report. However, unlike saline solution, naloxone, 8 mg, decreased significantly the analgesia induced by nitrous oxide. In 13 subjects, naloxone, 4 mg, also decreased significantly the effect of nitrous oxide analgesia in comparison with saline solution. Naloxone showed its reversal effect mainly on sensory response rating obtained during the painful stages of ischemia, between 11 and 15 min. The results suggest that analgesia induced by nitrous oxide may be partly related to the opiate receptor--endorphin system in man.

Topics: Analgesia; Arm Injuries; Drug Antagonism; Humans; Ischemia; Male; Naloxone; Nitrous Oxide; Pain; Tourniquets

Sixteen healthy subjects participated in an investigation of the interactive effects of naloxone and personal expectations of control, stress, and anxiety, on time tolerance to ischemic pain. Control and anxiety levels provided no significant naloxone-saline discriminations, but there was a significant interaction between stress levels and naloxone-induced reduction in tolerance to ischemia. This finding suggests that activity in the opiate system may be a function of the modifying influences of variable attitudes to environmental stress. A primary analgesic role for the endorphins is challenged, however, by the findings that tolerance levels failed to reveal naloxone reactors and stress levels were not significantly associated with differences in tolerance. The latter, on the other hand, correlated significantly with control and anxiety levels, indicating that further research is needed to clarify the complex relationship between these three variables and their effects on the modulation of pain perception.

Topics: Adult; Attitude; Female; Humans; Ischemia; Male; Naloxone; Pain; Sex Factors; Stress, Psychological

The hypothesis that painful stimuli activate the endogenous opioid (endorphin) system in humans was tested by examining the effect of the opiate antagonist naloxone on experimentally induced ischemic pain and on subjective mood ratings. Intravenous injections of saline or naloxone hydrochloride (2 and 10 mg) were administered under double-blind conditions to 12 subjects. Naloxone did not affect the pain ratings. However, a significant dose-related effect of naloxone on tension-anxiety was found, suggesting that the endorphins. like exogenously administered opiates, may have antianxiety properties.

Topics: Adult; Anxiety; Arm; Clinical Trials as Topic; Emotions; Female; Humans; Ischemia; Male; Naloxone; Pain; Surveys and Questionnaires

Topics: Buprenorphine; Constriction, Pathologic; Fingers; Humans; Hydromorphone; Injections, Intra-Arterial; Ischemia; Male; Middle Aged; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Peripheral Vascular Diseases; Toes

Chronic limb ischaemia, characterized by inflammatory mediator release and a low extracellular pH, leads to acid-sensing ion channel (ASIC) activation and reflexively increases mean arterial pressure; endomorphin release is also increased under inflammatory conditions. We examined the modulation of ASIC currents by endomorphins in sensory neurons from rats with freely perfused and ligated femoral arteries: peripheral artery disease (PAD) model. Endomorphins potentiated sustained ASIC currents in both groups of dorsal root ganglion neurons, independent of mu opioid receptor stimulation or G protein activation. Intra-arterial administration of lactic acid (to simulate exercising muscle and evoke a pressor reflex), endomorphin-2 and naloxone resulted in a significantly greater pressor response than lactic acid alone, while administration of APETx2 inhibited endomorphin's enhancing effect in both groups. These results suggest a novel role for endomorphins in modulating ASIC function to effect lactic acid-mediated reflex increase in arterial pressure in patients with PAD.. Chronic muscle ischaemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischaemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex. In rat dorsal root ganglion (DRG) neurons, exposure to E-2 in acidic solutions significantly potentiated ASIC currents when compared to acidic solutions alone. The potentiation was significantly greater in DRG neurons isolated from rats whose femoral arteries were ligated for 72 h. Sustained ASIC current potentiation was also observed in neurons pretreated with pertussis toxin, an uncoupler of G proteins and MOR. The endomorphin-mediated potentiation was a result of a leftward shift of the activation curve to higher pH values and a slight shift of the inactivation curve to lower pH values. Intra-arterial co-administration of lactic acid and E-2 led to a significantly greater pressor reflex than lactic acid alone in the presence of naloxone. Finally, E-2 effects were inhibited by pretreatment with the ASIC3 blocker APETx2 and enhanced by pretreatment with the ASIC1a blocker psalmotoxin-1. These findings have uncovered a novel role of endomorphins by which the opioids can enhance the lactic acid-mediated reflex increase in arterial pressure that is MOR stimulation-independent and APETx2-sensitive.

Topics: Acid Sensing Ion Channel Blockers; Acid Sensing Ion Channels; Action Potentials; Analgesics, Opioid; Animals; Blood Pressure; Cell Line; Cells, Cultured; Drug Synergism; Ganglia, Spinal; Hindlimb; Ischemia; Lactic Acid; Male; Mice; Naloxone; Oligopeptides; Peripheral Arterial Disease; Rats; Rats, Sprague-Dawley; Reflex; Sensory Receptor Cells

Hepatic injury induced by ischemia-reperfusion (I/R) after transplantation or lobectomy is a major clinical problem. The potential benefit of remifentanil in these hepatic surgeries remains unknown. The current study investigated whether remifentanil protects the liver against I/R injury in a rat model and whether the underlying mechanism involves the modulation of interleukin (IL)-18 signaling.. Male Sprague-Dawley rats were subjected to 45 minutes of partial hepatic ischemia followed by 6 hours of reperfusion. Then, they received an intravenous saline or remifentanil (0.4, 2, or 10 μg/kg per minute) infusion from 30 minutes before ischemia until the end of ischemia with or without previous administration of naloxone, a nonselective opioid receptor antagonist. Serum aminotransferase, hepatic morphology, and hepatic neutrophil infiltration were analyzed. The expression of hepatic IL-18; IL-18-binding protein (BP); and key cytokines downstream of IL-18 signaling were measured.. Remifentanil significantly decreased serum aminotransferase levels and profoundly attenuated the liver histologic damages. Liver I/R injury increased the expression of both hepatic IL-18 and IL-18BP. Although remifentanil pretreatment significantly decreased I/R-induced IL-18 expression, it further upregulated IL-18BP levels in liver tissues. The I/R-induced increases of hepatic interferon-γ, tumor necrosis factor-α and IL-1β expression, and neutrophil infiltration were also significantly reduced by remifentanil. Naloxone inhibited the remifentanil-induced downregulation of IL-18, but not the elevation of IL-18BP, and significantly attenuated its protective effects on liver I/R injury.. Remifentanil protects the liver against I/R injury. Modulating the hepatic IL-18/IL-18BP balance and inhibiting IL-18 signaling mediate, at least in part, the hepatoprotective effects of remifentanil.

Topics: Analgesics, Opioid; Animals; Gene Expression Regulation; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Interferon-gamma; Interleukin-18; Ischemia; Liver; Male; Naloxone; Neutrophils; Peroxidase; Piperidines; Rats; Rats, Sprague-Dawley; Remifentanil; Reperfusion Injury; Signal Transduction; Transaminases

rIPC (remote ischaemic preconditioning) is a phenomenon whereby short periods of ischaemia and reperfusion of a tissue or organ (e.g. mesentery, kidney) can protect a distant tissue or organ (e.g. heart) against subsequent, potentially lethal, ischaemia. We, and others, have shown that transient limb ischaemia can provide potent myocardial protection experimentally and clinically during cardiac surgery. Nonetheless, our understanding of the signal transduction from remote stimulus to local effect remains incomplete. The aim of the present study was to define the humoral nature of rIPC effector(s) from limb ischaemia and to study their local effects in isolated heart and cardiomyocyte models. Using a Langendorff preparation, we show that infarct size after coronary artery ligation and reperfusion was substantially reduced by rIPC in vivo, this stimulus up-regulating the MAPKs (mitogen-activating protein kinases) p42/p44, and inducing PKCepsilon (protein kinase Cepsilon) subcellular redistribution. Pre-treatment with the plasma and dialysate of plasma (obtained using 15 kDa cut-off dialysis membrane) from donor rabbits subjected to rIPC similarly protected against infarction. The effectiveness of the rIPC dialysate was abrogated by passage through a C18 hydrophobic column, but eluate from this column provided the same level of protection. The dialysate of rIPC plasma from rabbits and humans was also tested in an isolated fresh cardiomyocyte model of simulated ischaemia and reperfusion. Necrosis in cardiomyocytes treated with rIPC dialysate was substantially reduced compared with control, and was similar to cells pre-treated by 'classical' preconditioning. This effect, by rabbit rIPC dialysate, was blocked by pre-treatment with the opiate receptor blocker naloxone. In conclusion, in vivo transient limb ischaemia releases a low-molecular-mass (<15 kDa) hydrophobic circulating factor(s) which induce(s) a potent protection against myocardial ischaemia/reperfusion injury in Langendorff-perfused hearts and isolated cardiomyocytes in the same species. This cardioprotection is transferable across species, independent of local neurogenic activity, and requires opioid receptor activation.

Topics: Animals; Blood; Dialysis Solutions; Hindlimb; Humans; Ischemia; Ischemic Preconditioning, Myocardial; Ligation; Muscle, Skeletal; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; Naloxone; Narcotic Antagonists; Rabbits; Random Allocation; Receptors, Opioid

Severe haemorrhage leads to a reflex bradycardia and hypotension. This is thought to be protective, but is attenuated by both concomitant musculoskeletal injury and exogenous morphine. The aim of this study was to determine whether the injury-induced attenuation of the response to severe haemorrhage could be blocked by naloxone. Male Wistar rats, terminally anaesthetized with alphadolone/alphaxalone (19-20 mg kg(-1) h(-1)I.V.), were randomly allocated to one of four groups. In groups I and IV, haemorrhage was simple [40% of estimated total blood volume (BV)], while in groups II and III it was initiated 10 min after the onset of bilateral hindlimb ischaemia (a model of musculoskeletal injury). Groups I and II received 20 microl of 0.9% saline intracerebroventricularly (I.C.V.) immediately before haemorrhage, while groups III and IV received 20 microg of naloxone I.C.V., in the same volume. In group I, the bradycardia reached its peak after the loss of 32.8 +/- 0.3% BV (mean +/- S.E.M.). Blood pressure did not fall significantly until the loss of 15.0 +/- 3.0% BV. The response in group IV was not significantly different from group I. By contrast, the bradycardia was absent after similar blood losses in groups II and III, while hypotension was attenuated. These results indicate that naloxone, at a dose known to be effective in blocking mu-opioid receptors and preventing other aspects of the response to injury, does not prevent the injury-induced attenuation of the response to severe haemorrhage. Thus the attenuation of the response to blood loss by injury is unlikely to be mediated via the mu-opioid receptors.

Topics: Animals; Blood Pressure; Blood Volume; Bradycardia; Heart Rate; Hemorrhage; Hindlimb; Hypotension; Ischemia; Male; Musculoskeletal System; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Receptors, Opioid, mu

Transient global ischemia is a neuronal insult that induces delayed, selective death of hippocampal CA1 pyramidal neurons. A mechanism underlying ischemia-induced cell death is activation of the gene silencing transcription factor REST (repressor element-1 silencing transcription factor)/NRSF (neuron-restrictive silencing factor) and REST-dependent suppression of the AMPA receptor subunit GluR2 in CA1 neurons destined to die. Here we show that REST regulates an additional gene target, OPRM1 (mu opioid receptor 1 or MOR-1). MORs are abundantly expressed by basket cells and other inhibitory interneurons of CA1. Global ischemia induces a marked decrease in MOR-1 mRNA and protein expression that is specific to the selectively vulnerable area CA1, as assessed by quantitative real-time RT-PCR, Western blotting, and ChIP. We further show that OPRM1 gene silencing is REST-dependent and occurs via epigenetic modifications. Ischemia promotes deacetylation of core histone proteins H3 and H4 and dimethylation of histone H3 at lysine-9 (H3-K9) over the MOR-1 promoter, an signature of epigenetic gene silencing. Acute knockdown of MOR-1 gene expression by administration of antisense oligodeoxynucleotides to hippocampal slices in vitro or injection of the MOR antagonist naloxone to rats in vivo affords protection against ischemia-induced death of CA1 pyramidal neurons. These findings implicate MORs in ischemia-induced death of CA1 pyramidal neurons and document epigenetic remodeling of expression of OPRM1 in CA1 inhibitory interneurons.

Topics: Animals; Cell Survival; Epigenesis, Genetic; Hippocampus; Histones; Ischemia; Male; Naloxone; Narcotic Antagonists; Neurons; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; RNA, Messenger; Time Factors

Opioid receptors have been implicated in protecting several organ systems from ischaemic events. The authors have studied the effects of opioid receptors on random-pattern skin flap survival. Sixty-nine male Sprague-Dawley rats were used. Bipedicled dorsal skin flaps (2 x 8 cm) were elevated at the midline. Different doses of morphine (0.01, 0.1, 1 and 5 mg/flap) were administered locally in the cranial half of the flap and systemically through intraperitoneal injections (5 and 10 mg/kg). In another experiment, 0.4 mg/flap of naloxone was injected followed by 5 mg/flap injection of morphine to determine whether the effect of morphine is receptor mediated. The role of the opioid receptors in the ischaemic preconditioning (IPC) phenomenon was investigated by administration of naloxone (0.4 mg/flap) 1 h before clamping the cranial pedicle for 20 min followed by 40 min of reperfusion. Appropriate control groups were included. The cranial pedicle was cut 2 h after saline or drug administration in all groups and flap survival area was evaluated on the seventh postoperative day. Local administration of morphine in higher doses (1 and 5 mg/flap) significantly reduced the amount of flap necrosis when compared to that of the control cohort (P < 0.05). Naloxone abolished this protective effect of morphine. Furthermore naloxone significantly decreased the anti-ischaemic effect of the IPC. Systemic administrations of morphine had no significant effect on flap survival area in compare with the control group.

Topics: Animals; Dose-Response Relationship, Drug; Injections, Intraperitoneal; Ischemia; Male; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Necrosis; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Skin; Surgical Flaps; Tissue Survival

We have shown that a reverse-phase concentrate generated from the effluent of preconditioned (PC) rabbit hearts evokes a cardioprotective effect in virgin acceptor hearts. With the use of a model of sustained (1 h) simulated ischemia in isolated, spontaneously contracting rabbit jejunum, our current aims were to 1) determine whether protective factor(s) released from PC hearts can improve ischemic tolerance in noncardiac tissue; and 2) obtain preliminary insight into the mediator(s) involved in triggering and eliciting this remote protection. Recovery of contractile force following reoxygenation (our index of ischemic tolerance) was enhanced in jejunal segments pretreated with concentrate generated from PC hearts (33 +/- 3% of baseline, P < 0.01) versus segments that received no concentrate (21 +/- 2%) and segments treated with concentrate from normoxic hearts (16 +/- 3%; P < 0.01). Protection achieved with PC concentrate was attenuated by coadministration of naloxone or glibenclamide, thereby implicating the involvement of opioids and ATP-sensitive potassium channels. Moreover, evaluation of purified subfractions of the crude PC concentrate identified a specific bioactive fraction that may participate in triggering the improved jejunal ischemic tolerance.

Topics: Animals; Chromatography, High Pressure Liquid; Glyburide; In Vitro Techniques; Ischemia; Ischemic Preconditioning, Myocardial; Jejunum; Mesentery; Muscle Contraction; Myocardium; Naloxone; Narcotic Antagonists; Potassium Channel Blockers; Potassium Channels; Rabbits; Receptors, Opioid; Tissue Extracts

This study investigated the protective effects of ischemic preconditioning on intestinal ischemic injury and the role of endogenous opioid peptides (EOP) in these effects. Ischemia-reperfusion (I/R) induced by 30-min of ischemia and 60-min of reperfusion significantly increased the levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) and resulted in serious intestinal edema (wet weight/dry weight). The ischemic preconditioning (PC) elicited by three 8-min occlusion periods interspersed with 10-min reperfusion markedly attenuated intestinal injury caused by ischemia-reperfusion. Pretreatment with morphine (300 microg x kg(-1), i.v.) 10-min before ischemia and reperfusion mimicked the protection produced by PC. Naloxone (3 mg x kg(-1), i.v.) abolished the protection of morphine-induced preconditioning and ischemic preconditioning in rat intestine. However, there were no changes between naloxone alone and control groups. Treatment with naloxone before ischemia-reperfusion had no effect on animals compared with the I/R group. In addition, we also measured the content of endogenous opioid peptides (Leu-enkephalin) in the effluent which was collected before and during preconditioning. It was shown that the release of leu-enkephalin was markedly increased during preconditioning. These results suggested that EOP might play an important role in PC in rat small intestine.

Topics: Analgesics, Opioid; Animals; Drug Interactions; Edema; Enkephalin, Leucine; Intestinal Diseases; Intestinal Mucosa; Intestine, Small; Ischemia; Ischemic Preconditioning; L-Lactate Dehydrogenase; Male; Malondialdehyde; Morphine; Naloxone; Narcotic Antagonists; Opioid Peptides; Rats; Rats, Wistar; Receptors, Opioid; Reperfusion Injury

Effects of GABAergic drugs on the recovery of reflex potentials after spinal cord ischemia were examined in anesthethized spinal cats. Monosynaptic reflex (MSR) and polysynaptic reflex (PSR) potentials, elicited by electrical stimulation of the tibial nerve in spinal cats, were recorded from the lumbo-sacral ventral root. The spinal reflex potentials were immediately depressed by occlusion of the thoracic aorta and the bilateral mammary arteries for 10 min. The potentials recovered gradually to the control level within 90 min after reperfusion. Pretreatment with bicuculline (0.3 mg/kg, i.v.), a GABA antagonist, or semicarbazide (200 mg/kg, i.v.), an inhibitor of GABA synthesis, accelerated the recovery of PSR potentials after the removal of the arterial occlusion. In contrast, pretreatment with aminooxyacetic acid (10 mg/kg, i.v.), an inhibitor of GABA degradation, retarded the recovery of PSR potentials, and this effect was overcome by the addition of the opioid antagonist naloxone (10 mg/kg, i.v.). These results suggest that the GABAergic system retards the recovery of PSR potentials after a brief spinal cord ischemia, which can be antagonized by naloxone.

Topics: Animals; Bicuculline; Cats; Female; Ischemia; Male; Membrane Potentials; Naloxone; Receptors, GABA; Reflex; Spinal Cord Injuries; Time Factors

We have investigated the involvement of the GABAA-benzodiazepine receptor complex in nociceptive activity of convergent neurones in the spinal cord during ischaemia and reperfusion of their receptive fields on the rat's tail. In enflurane anaesthetized rats, extracellular recordings were made from convergent neurones located throughout the dorsal horn before, during and after 30 min of ischaemia. Following intrathecal saline pretreatment, there was a significant increase in spontaneous firing rate during ischaemia (219 +/- 21%, P < 0.02, n = 10) which persisted during reperfusion. After 10 min of reperfusion, the neurones exhibited a greater response than before ischaemia to both innocuous brush (54 +/- 11%, P < 0.05, n = 10) and noxious pinch (72 +/- 14%, P < 0.02, n = 10) and the enhanced sensitivity persisted over the 60-min reperfusion period. During reperfusion, receptive field size increased in most neurones tested. Intrathecal diazepam (100 and 500 micrograms) abolished the hyperexcitability and the hypersensitivity to both innocuous and noxious mechanical stimulation during reperfusion. The highest dose of diazepam (500 micrograms) also attenuated the increase in spontaneous firing rate during ischaemia. Diazepam, at the doses tested, had no effect on receptive field enlargements during reperfusion. The effect of 100 micrograms of diazepam was partially reversed by flumazenil (1 mg/kg i.p.) but not by naloxone (1 mg/kg i.p.). In the absence of ischaemia, diazepam had no effect on spontaneous firing rate nor on the responses to innocuous or noxious mechanical stimulation. Our results support an antinociceptive role for benzodiazepines in the dorsal horn elements responsible for reperfusion hyperalgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Diazepam; Electrophysiology; Flumazenil; Ischemia; Male; Naloxone; Neurons; Physical Stimulation; Rats; Rats, Sprague-Dawley; Reperfusion; Spinal Cord; Tail

The efficacy of naloxone (NL), a broad spectrum opioid antagonist, on retinal ischemia, was evaluated in a rat model of retinal ischemia with histopathologic and morphometric criteria. Two intraperitoneal injections of naloxone 3 mg/kg given immediately and 6 hr after reperfusion showed beneficial effects to the retina as evaluated at 2, 7, and 14 days after reperfusion. Morphologically, the naloxone-treated group showed better-preserved ganglion cells, nerve fiber layer, and inner nuclear layer. Morphometrically, in the treated groups, inner retinal thickness at all three time points and ganglion cell counts at 7 days showed higher values than vehicle controls. This beneficial effect of naloxone was dose-dependent with a minimal effective total dose of 6 mg/kg. A possible role of opiate receptors in retinal ischemia is suggested.

Topics: Animals; Cell Count; Dose-Response Relationship, Drug; Injections, Intraperitoneal; Ischemia; Male; Naloxone; Nerve Fibers; Neurons; Rats; Rats, Inbred Lew; Retinal Ganglion Cells; Retinal Vessels

1. An investigation into whether reperfusion hyperalgesia is modulated by prior systemic administration of two benzodiazepine agonists (diazepam and chlordiazepoxide), and an antagonist (flumazenil) was conducted. 2. Transient ischaemia was induced in conscious rats by applying an inflatable tourniquet to the base of the tail; when the rats exhibited a co-ordinated escape response, the tourniquet was deflated and reperfusion of the tail was allowed. Reperfusion hyperalgesia manifested as a decrease in tail flick latency, following tail immersion in 49 degrees C water, after the release of the tourniquet. 3. Intraperitoneal administration of diazepam, chlordiazepoxide and flumazenil had no effect on the co-ordinated escape to the noxious ischaemic stimulus nor on tail flick latency after application of a sham tourniquet. 4. The hyperalgesia evident during reperfusion, was abolished by diazepam (1 and 5 mg kg-1) and chlordiazepoxide (5 and 25 mg kg-1). The antihyperalgesic effects of both diazepam (5 mg kg-1) and chlordiazepoxide (25 mg kg-1) were inhibited by flumazenil (1 mg kg-1). 5. Rotarod performance was impaired in rats given diazepam and chlordiazepoxide at the same doses at which the benzodiazepines were antihyperalgesic. The impairment to motor function did not extend to the motor systems involved in the tail flick response. 6. In conclusion, benzodiazepines have antinociceptive properties during hyperalgesia.

Topics: Animals; Behavior, Animal; Benzodiazepines; Chlordiazepoxide; Depression, Chemical; Diazepam; Dose-Response Relationship, Drug; Flumazenil; Hyperalgesia; Ischemia; Male; Motor Activity; Naloxone; Pain Measurement; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Reperfusion Injury; Tail

The effects of continuous naloxone infusion on the response to intestinal ischemia-reperfusion were studied in a rat model. Naloxone was given as a bolus injection (2 mg/kg bw) followed by a continuous infusion (4 mg/kg bw/h) starting before (-10 min) intestinal ischemia was applied (0-60 min) and continuing 2 h after reperfusion of the intestine. Blood pressure, acidosis and survival were determined. Saline-infused shocked rats and untreated shocked rats served as comparisons and non-shocked animals as controls. Blood pressure was slightly higher before and during the continuous naloxone infusion but did not differ after reperfusion in the three shock groups. Acidosis was less pronounced in naloxone compared to untreated shocked rats. Survival rates were significantly higher in naloxone-treated shocked rats compared to untreated shock and significantly lower in saline treated shocked rats compared to non-shocked controls. In conclusion a naloxone effect on acidosis and survival in shock after intestinal ischemia and reperfusion is possible.

Topics: Acid-Base Equilibrium; Acidosis; Animals; Blood Pressure; Hematocrit; Infusions, Intravenous; Intestines; Ischemia; Naloxone; Rats; Rats, Wistar; Reperfusion; Shock

We have investigated the effects of systemic administration of two N-methyl-D-aspartate (NMDA) receptor antagonists and two opiate agonists on nociception during and after tail ischaemia in conscious rats. The two NMDA receptor antagonists, D-2-amino-5-phosphonovalerate (APV) and ketamine hydrochloride, did not alter tail flick latencies in rats not subjected to ischaemia but inhibited post-ischaemic hyperalgesia (PIH) in a dose-dependent manner. Neither of these agents impaired motor function of the rats, as assessed by rotarod performance, suggesting a purely sensory antinociceptive effect. The antinociceptive effect of APV during reperfusion following ischaemia was not antagonised by the mu-opiate receptor antagonist naloxone (1 mg/kg). The two opiate receptor agonists, morphine and pethidine, increased tail flick latencies in rats not subjected to ischaemia, inhibited PIH in a dose-dependent manner, and also caused significant motor malfunction, all in naloxone-reversible fashion. We conclude that the role of the NMDA receptor in mediating afferent nociceptive traffic is confined to its involvement in neuronal events mediating hyperalgesia.

Topics: 2-Amino-5-phosphonovalerate; Animals; Hot Temperature; Hyperalgesia; Ischemia; Male; Meperidine; Morphine; Naloxone; Nociceptors; Rats; Rats, Inbred Strains; Reaction Time; Receptors, N-Methyl-D-Aspartate; Receptors, Opioid; Reperfusion; Tail

The spinal reflex potentials elicited by electrical stimulation of the tibial nerve were recorded from the lumbo-sacral ventral root in spinal cats. When the thoracic aorta and the bilateral internal mammary arteries were occluded for 10 min, the potentials were completely depressed. Reappearance of these potentials could be observed at about 10 min after removal of the occlusion and they gradually recovered. Intravenous injection of naloxone (1 or 10 mg/kg) or levallorphan (0.1 mg/kg) together with removal of occlusion significantly promoted the recovery of the polysynaptic reflex potential. Morphine (5 mg/kg) showed no particular effect on the recovery of potentials. Furthermore, pretreatment with morphine (5 mg/kg) did not influence the effects of these opioid antagonists. These results suggest that naloxone and levallorphan may preserve or potentiate the interneuronal activities of the lumbo-sacral spinal cord under the ischemic condition and that the effects may not be mediated through morphine-like opioid receptors.

Topics: Animals; Blood Pressure; Cats; Electric Stimulation; Female; Ischemia; Levallorphan; Male; Membrane Potentials; Naloxone; Reflex; Spinal Cord; Time Factors

Topics: Animals; Calcium Channel Blockers; Hepatic Artery; Ischemia; Liver; Nalbuphine; Naloxone; Naltrexone; Narcotic Antagonists; Portal Vein; Rats; Rats, Inbred Strains; Verapamil

Topics: Animals; Intestine, Small; Ischemia; Mesenteric Arteries; Naloxone; Naltrexone; Narcotic Antagonists; Necrosis; Rats; Rats, Inbred Strains; Time Factors

Topics: Animals; Intestine, Small; Ischemia; Mesenteric Arteries; Mesenteric Vascular Occlusion; Naloxone; Rats; Rats, Inbred Strains

The purpose of this study was to determine whether gamma-hydroxybutyrate provides protection against intestinal ischemia/reperfusion injury and to compare its effect with that of allopurinol and vitamin E. Thirty minutes of total regional ischemia, followed by 3 hours of reperfusion, produced intestinal damage that was completely prevented by gamma-hydroxybutyrate pretreatment. Naloxone partially blocked this protective effect. Allopurinol provided only partial protection against this injury, whereas vitamin E provided none. Treatment with gamma-hydroxybutyrate after ischemia but before reperfusion also provided significant protection. This study clearly demonstrates that gamma-hydroxybutyrate provides significant protection against intestinal ischemic injury and that it may do so via an opiate receptor-mediated mechanism.

Topics: Allopurinol; Animals; Cricetinae; Hydroxybutyrates; Intestines; Ischemia; Male; Mesocricetus; Naloxone; Reperfusion Injury; Sodium Oxybate; Vitamin E

The characteristics of opioid receptors were studied by the binding of (3H)naloxone in ischemic lumbar spinal cord segments of newborn pigs. Ischemia was elicited by ligating the aorta for 30 min. The number of millimicron opioid receptors decreased, from 117 +/- 18 to 89 +/- 11 fmol/mg protein, while the Kd value was not significantly altered. It is concluded that even a relatively brief interruption of the oxygen supply may cause severe damage in the lumbar spinal cord of the newborn pig, affecting the opioid neurotransmission. The animal model employed here might be suitable for studying the effects of hypoxia in newborns and children during chest operations involving the descending aorta.

Topics: Animals; Animals, Newborn; Female; Ischemia; Kinetics; Male; Naloxone; Receptors, Opioid; Spinal Cord; Swine

Plasma levels of catecholamines and neuropeptides (met-enkephalin, ME; neurotensin, NT; neuropeptide Y, NPY; peptide YY, PYY; vasoactive intestinal polypeptide, VIP; cholecystokinin, CCK; bombesin, BMB) were examined in the femoral artery (FA), adrenal vein (AD), and portal vein (PV), in eight cats under halothane anesthesia at baseline (S1), at the end of a 2-hr ligation period of the major splanchnic arteries (celiac trunk, superior and inferior mesenteric arteries) (S2), immediately (S3) and 30 min (S4) after splanchnic reperfusion, and after the administration of naloxone (1 mg/kg, i.v.) (S5). During S2, there was a significant increase in portal vein VIP levels, while the other variables (hemodynamics, hormone levels) remained unchanged. During early shock (S3), significant (10- to 30-fold) increases in adrenal secretion of all catecholamines, ME, NT, NPY, and PYY occurred, while VIP and PYY were significantly released into the PV, and two- to tenfold increases in femoral artery catecholamine and ME levels were observed. Later shock (S4) led to a further fivefold increase, compared to S3, in adrenal release of norepinephrine (NE), dopamine (DA), and ME. Following naloxone administration (S5), the adrenal medullary release of NE, epinephrine (EPI), DA, NT, and NPY was significantly (twofold) increased; however, the animals' hemodynamic situation did not improve.

Topics: Adrenal Glands; Animals; Bombesin; Catecholamines; Cats; Cholecystokinin; Enkephalin, Methionine; Hemodynamics; Intestinal Mucosa; Ischemia; Ligation; Mesenteric Arteries; Naloxone; Neuropeptide Y; Neuropeptides; Neurotensin; Peptide YY; Peptides; Shock, Septic; Vasoactive Intestinal Peptide

The effect of trauma on human thermoregulation has been studied using a behavioural test and the vascular response to cold exposure. It was confirmed, in controls, that a pleasurable temperature for the hand (Thand) depended on core temperature (Tc) to which it was negatively related. Shortly after moderately severe fractures in a leg this relationship was lost and in the patients the slope of this regression line was not significantly different from zero and they usually chose a Thand towards the upper end of the normal range irrespective of Tc. This effect was not imitated in controls by removing 500 ml blood but Thand was increased by occluding the circulation to one leg. Naloxone did not alter Thand in controls but when given in a suitable dose it reduced the rise in Thand during a short period of limb ischaemia. Immersing one hand and forearm in water at 17 degrees C reduced the blood flow through the contralateral forearm and hand. The reduction in flow was positively related to the initial rate of flow in both controls and injured but the slope of the regression line was significantly less after injury. It is concluded that thermoregulation is affected by trauma in man.

Topics: Adolescent; Adult; Aged; Blood Vessels; Body Temperature; Body Temperature Regulation; Extremities; Female; Hand Injuries; Hemorrhage; Humans; Ischemia; Male; Middle Aged; Naloxone; Pleasure-Pain Principle; Wounds and Injuries

The contribution of endogenous opioid peptides to the development of circulatory derangement in severe shock was studied using naloxone. A standardized intestinal shock was induced in rats by applying a pressure of 120 cm water on the mesenteric vessels for 60 min. The rats were then given either saline or naloxone. Mean arterial blood pressure improved and a less severe acidosis resulted in naloxone-treated animals compared to saline-treated. No differences were found in hematocrit, the degree of small intestinal mucosal lesions, or survival rates after 7 days comparing naloxone and saline treatment. Survival time increased after naloxone but not after saline treatment. The results support the hypothesis that endogenous opioid peptides contribute to cardiovascular collapse in intestinal shock.

Topics: Acid-Base Equilibrium; Animals; Blood Pressure; Female; Hematocrit; Hemoglobins; Intestinal Mucosa; Intestines; Ischemia; Male; Naloxone; Rats; Rats, Inbred Strains; Shock

The effect of naloxone on a number of experimental shock models, using the anaesthetized rat, was studied with special emphasis on mean arterial blood pressure (MABP) and chance of survival. Only a slight increase in MABP was noted in haemorrhagic shock models whereas survival was not affected. Naloxone was without effect in endotoxin shock (i.p. administration of endotoxin). In endotoxin shock (i.v. administration) naloxone increased MABP especially at a high dose of endotoxin. Although survival time was prolonged, the chance of permanent survival was not improved. Naloxone had practically no effect in anaphylactic shock and intestinal ischaemia shock. It is concluded that if naloxone has any effect it is relatively slight. However, this does not exclude the possibility that naloxone might still be considered as an adjunct to other forms of shock treatment at least in certain types of shock.

Topics: Anaphylaxis; Animals; Blood Pressure; Female; Intestines; Ischemia; Male; Naloxone; Rats; Rats, Inbred Strains; Shock; Shock, Hemorrhagic; Shock, Septic; Time Factors

The authors have studied the protection against ischemic damage to rabbit spinal cord by pretreatment with agents that block neuronal activity and directly or indirectly reduce tissue metabolism. Hypothermia, thiopental, magnesium, lidocaine, and naloxone were used to pretreat the spinal cord prior to ischemia. Hypothermia and thiopental provided comparable protection: they each increased the duration of ischemia required to produce neurological deficits in 50% of the animals from 26 to 41 minutes. They also increased from 10 to 30 minutes the time that the postsynaptic waves of the spinal somatosensory evoked potential (SSEP) could be absent and the animal still have neurological recovery. Hypothermia and thiopental, when used together, increased the duration of ischemia required to produce neurological deficits to 57 minutes in 50% of the animals. Naloxone increased the duration of ischemia required to produce neurological deficits to 36 minutes in 50% of the animals, and increased to 20 minutes the time that the postsynaptic waves of the SSEP could be absent and the animal still have neurological recovery. Magnesium pretreatment improved neurological outcome, possibly by improving collateral circulation as the SSEP did not fail completely during aortic occlusion in all animals. Lidocaine was not beneficial, perhaps because of the prolonged hypotension that resulted.

Topics: Animals; Aorta, Abdominal; Evoked Potentials, Somatosensory; Hypothermia, Induced; Ischemia; Lidocaine; Magnesium Sulfate; Naloxone; Rabbits; Spinal Cord; Thiopental

Temporary aortic occlusion produces a consistent degree of spinal cord injury in the unanesthetized rabbit. This 'spinal stroke' model was utilized to examine the potential therapeutic effects of the opiate antagonist naloxone in central nervous system ischemia. Naloxone treatment resulted in dose-related enhancement of motor recovery; greatest functional recovery was observed in rabbits treated with a dose of 2 mg/kg per h. This dose compares well with the high doses of naloxone shown to have a beneficial effect in other experimental models of stroke and spinal injury. In contrast, clinical stroke studies, which have been largely unsuccessful, have utilized naloxone doses which are several orders of magnitude lower than those successfully employed in experimental models.

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Ischemia; Naloxone; Rabbits; Spinal Cord; Spinal Cord Injuries

Thirty subjects were given a placebo (intravenous saline), which was described as a known pain killer, once a week for 3 consecutive weeks. Experimental ischemic arm pain was produced prior to the placebo and again 1 h later. In a double blind procedure, half of the subjects received 10 mg of naloxone after placebo; the remaining subjects received naloxone vehicle. In addition to the placebo session, there were control and naloxone sessions each week to determine the normal changes in pain and the effect of naloxone on the pain, respectively, when no placebo was given. Significant placebo-induced analgesia was demonstrated, and a group of consistent placebo responders was identified. Although naloxone alone had no effect on the experimental pain, naloxone diminished the analgesic effectiveness of the placebo, suggesting that endogenous opioids are involved in producing placebo-induced analgesia.

Topics: Adult; Analgesia; Arm; Double-Blind Method; Endorphins; Female; Humans; Ischemia; Male; Naloxone; Pain; Pain Management; Placebos; Random Allocation; Receptors, Opioid

Ischemic pain was produced by a blood pressure cuff placed to the arm of healthy human subjects for 15 min which produced a mean pain score of 59% (visual analogue scale). Ischemia induced a significant dental pain threshold elevation (mean 67%) and 2 mg of naloxone did not reduce it. Thermal sensitivity of the upper lip had a tendency to reduction during ischemia and 2 mg of naloxone reduced this effect. Tactile thresholds in the forehead or in the contralateral arm were not markedly elevated. Neither ACTH nor prolactin level in the plasma was related to the dental pain threshold elevation during ischemia. The findings of the present study suggest that ischemic pain nonsegmentally produces a predominant inhibition of responses to thin afferents. Endogenous opioids may markedly contribute to the reduction of thermal sensitivity induced by ischemia, but their contribution to dental pain threshold elevations seems to be less important. Stress or other adenohypophyseal mechanisms involving the release of ACTH or prolactin do not explain the effects of ischemia found in the present study.

Topics: Adrenocorticotropic Hormone; Adult; Arm; Blood Pressure; Endorphins; Humans; Ischemia; Male; Naloxone; Pain; Prolactin; Regional Blood Flow; Tourniquets

The finding that naloxone reverses the arterial hypotension produced by bacterial endotoxin in the rat was confirmed and the effect of naloxone on the responses to another form of injury, limb ischaemia was studied. Naloxone had no effect on the fall in blood pressure and colon temperature or on behaviour and survival after bilateral hind-limb ischaemia. The ambient temperature threshold for the onset of shivering was depressed by limb ischaemia as in untreated rats. The increases in the plasma concentrations of glucose and corticosterone and the decrease in that of prolactin after limb ischaemia were unaltered by naloxone. In control rats naloxone reduced the ambient temperature threshold for the onset of shivering and the plasma prolactin concentration. It is concluded that the endogenous opioids do not play a very significant part in the responses to ischaemic limb trauma.

Topics: Animals; Blood Glucose; Blood Pressure; Body Temperature; Corticosterone; Extremities; Ischemia; Male; Naloxone; Pituitary Gland; Prolactin; Rats; Rats, Inbred Strains

The responses to work-test in ischemia (tourniquet technique), before and after I.V. injection of naloxone (2 mg) or saline, were investigated in healthy volunteers and patients suffering from various types of headache. The patients were examined during both painful and painless periods. We found that only the subjects suffering from migraine showed a significantly shortened pain tolerance at work-test in ischemia, after injection of naloxone, and only during painful periods. Psychogenic headache patients and migraine patients in painless periods showed responses during work-test similar to those in healthy volunteers, even after injection of naloxone. We believe that hyperalgesic effect of naloxone is due to involvement of beta-endorphin systems only during organic pain.

Topics: Adult; Arm; Double-Blind Method; Female; Headache; Humans; Ischemia; Male; Migraine Disorders; Naloxone; Pain; Sensory Thresholds; Sodium Chloride

The effect of naloxone on blood flow and somatosensory evoked potentials was studied in cats subjected to 400 gm-cm contusion injuries of the thoracic spinal cord. Eight cats were treated with 10 mg/kg naloxone 45 to 60 minutes after injury, 11 cats were given 10 ml of saline instead of naloxone, and six cats were neither injured nor treated. Hydrogen clearance was used to measure blood flow in the lateral white columns at the contusion site. Naloxone, given intravenously, significantly inproved the blood flow rates in the lateral column white matter. At 2 hours after injury, the mean blood flow in the saline-treated cats fell to 50% (p greater than 0.01) of preinjury flow rates, whereas it increased 6% (p greater than 0.50) in naloxone-treated cats, and 12% (p greater than 0.50) in uninjured cats. At the 3rd hour after injury, the respective flows fell 47% (p less than 0.01), and 6% (p greater than 0.50), and increased 15% (p greater than 0.50) of the preinjury flow rates. The naloxone-treated cats had striking preservation of sensory function and somatosensory evoked potentials at 24 hours after injury. At 24 hours, responses had returned in all the naloxone-treated cats and in only 11% of the saline-treated cats. The probability of this combination of events occurring by chance is 0.0030. The authors conclude that naloxone may be useful for the treatment of spinal cord injury. The mechanism of the effect is unknown.

Topics: Animals; Blood Pressure; Cats; Contusions; Evoked Potentials; Ischemia; Naloxone; Regional Blood Flow; Respiration; Spinal Cord; Spinal Cord Injuries

Hypnotic analgesia in some respects resembles opiate analgesia. We tested the hypothesis that some features of hypnotic analgesia are mediated through neuronal pathways activating specific opiate receptors in brain. The opiate antagonist naloxone had no effect on hypnotic analgesia in three subjects. Thus, the hypothesis was not confirmed.

Topics: Female; Humans; Hypnosis, Anesthetic; Ischemia; Male; Naloxone; Pain