naloxone and Pain--Intractable

In this paper the under-use of opioids for pain and symptom management is considered by explored by examining the history of the use of the opioid antagonist, naloxone.

Topics: Ethics, Medical; Humans; Naloxone; Narcotic Antagonists; Pain, Intractable; Palliative Care

A 57-year-old woman with metastasizing ovarian cancer and chronic renal failure was admitted for morphine treatment of an acute lumbospinal pain syndrome, ambulant treatment with analgesics having failed provide adequate pain relief. On admission due to pain the conscious patient presented with reduced general condition and lumbal pain sensitive to tapping. Lasègue's sign was positive on both sides, no other disturbed neurological functions were found.. On the 7th day of morphine administration she became somnolent and breathing became markedly depressed, indicating overdosage, metabolic and intracranial causes having been excluded. Naloxone, an opioid antagonist, was given i.v. and the breathing pattern improved. But drowsiness continued for another 48 hours and only regressed after repeated doses of naloxone.. Morphine-6-glucuronide (M6G), formed from morphine in the liver, accumulates in blood and penetrates the blood-brain barrier, binding with strong affinity to opiate receptors and exerts a strong analgesic effect. As M6G is excreted by the kidney, its concentration rises in renal failure and can lead to severe intoxication. Morphine dosage must therefore be carefully controlled in patients with renal failure.

Topics: Analgesics, Opioid; Diagnosis, Differential; Female; Humans; Kidney Failure, Chronic; Middle Aged; Morphine; Morphine Derivatives; Naloxone; Narcotic Antagonists; Ovarian Neoplasms; Pain, Intractable; Poisoning

During the past 15 years, we prospectively followed 68 patients with chronic pain syndromes who underwent deep brain stimulation (DBS). The objective of our study was to analyze the long-term outcomes to clarify patient selection criteria for DBS.. Patients were referred from a multidisciplinary pain clinic after conservative treatment failed. Electrodes for DBS were implanted within the periventricular gray matter, specific sensory thalamic nuclei, or the internal capsule. Each patient was followed on a 6-monthly follow-up basis and evaluated with a modified visual analog scale.. Follow-up periods ranged from 6 months to 15 years, with an average follow-up period of 78 months. The mean age of the 54 men and 14 women in the study was 51.3 years. Indications for DBS included 43 patients with failed back syndrome, 6 with peripheral neuropathy or radiculopathy, 5 with thalamic pain, 4 with trigeminal neuropathy, 3 with traumatic spinal cord lesions, 2 with causalgic pain, 1 with phantom limb pain, and 1 with carcinoma pain. After initial screening, 53 of 68 patients (77%) elected internalization of their devices; 42 of the 53 (79%) continue to receive adequate relief of pain. Therefore, effective pain control was achieved in 42 of 68 of our initially referred patients (62%). Patients with failed back syndrome, trigeminal neuropathy, and peripheral neuropathy fared well with DBS, whereas those with thalamic pain, spinal cord injury, and postherpetic neuralgia did poorly.. DBS in selected patients provides long-term effective pain control with few side effects or complications.

Topics: Adult; Aged; Back Pain; Denervation; Electric Stimulation Therapy; Electrodes, Implanted; Equipment Failure; Female; Follow-Up Studies; Herpesviridae Infections; Humans; Male; Middle Aged; Morphine; Naloxone; Neostriatum; Neuralgia; Nociceptors; Pain, Intractable; Periaqueductal Gray; Prospective Studies; Thalamic Nuclei; Treatment Outcome; Work Capacity Evaluation

Topics: Afferent Pathways; Animals; Brain; Brain Mapping; Cats; Electric Stimulation; Endorphins; Enkephalins; Humans; Mice; Naloxone; Neural Inhibition; Nociceptors; Pain; Pain, Intractable; Rats; Spinal Cord; Spinothalamic Tracts; Substance P; Substantia Gelatinosa

Some sources suggest that significant misuse of opioid drugs exists among patients with chronic pain. However, the risk factors and motivation behind their abuse may differ from those of other opioid abusers. This study sought to examine the abuse liability of oxycodone among patients with chronic, non-malignant pain who met the DSM-IV criteria for opioid abuse. Eighteen opioid-dependent patients with chronic pain lived on an in-patient unit of the New York State Psychiatric Institute during the 7-week study. Participants were given oral oxycodone (0, 10, 20, 40, and 60 mg/70 kg) while maintained on various doses of sublingual buprenorphine/naloxone (Bup/Nx; 2/0.5, 8/2, and 16/4 mg/day). Doses of both medications were administered under double-blind conditions. Oxycodone produced an overall positive, but less robust, subjective profile than previously reported in recreational opioid users without pain. Furthermore, unlike our findings in recreational opioid users and more similar to effects in non-drug-abusing individuals, oxycodone failed to serve as a reinforcer. As for the maintenance drug, Bup/Nx produced a dose-related reduction in some of the effects of acutely administered oxycodone. These data suggest that sublingual Bup/Nx has the potential as an analgesic medication and further research should investigate its use in treating patients with chronic pain who abuse opioids.

Topics: Adult; Analgesia; Analgesics, Opioid; Buprenorphine; Double-Blind Method; Drug Synergism; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Oxycodone; Pain, Intractable; Reinforcement Schedule

We investigated the role of the glutamatergic and endogenous opioidergic systems in the paradoxical pain evoked by the simultaneous application of innocuous warm and cold stimuli to the skin with a "thermal grill". Two parallel randomized, double-blind, cross-over studies, including two groups of 12 healthy volunteers, were carried out to compare the effects of i.v. ketamine or naloxone to those of placebo, on the sensations produced by a thermode (i.e. thermal grill) composed of six bars applied on the palmar surface of the right hand. The temperature of alternate (even- and odd-numbered) bars could be controlled independently by Peltier elements to produce various patterns of the grill. During each experimental session we measured the effects of ketamine, naloxone or placebo on the intensity of: (i) paradoxical pain; (ii) "normal" thermal (heat and cold) pain; and (iii) non-painful thermal (warm and cool) sensations. Ketamine administration resulted in a significant reduction of paradoxical pain intensity but did not alter normal pain or non-painful thermal sensations. By contrast, naloxone had no effect on paradoxical pain, normal pain or non-painful thermal sensations. This study demonstrates for the first time that the "thermal grill illusion of pain" can be modulated pharmacologically. This paradoxical pain, which involves the glutamatergic systems, acting through the NMDA receptors, but not the tonic endogenous opioids systems, might share some mechanisms with pathological pain.

Topics: Analgesics; Cold Temperature; Cross-Over Studies; Double-Blind Method; Excitatory Amino Acid Antagonists; Glutamic Acid; Hot Temperature; Humans; Hyperalgesia; Illusions; Ketamine; Naloxone; Narcotic Antagonists; Nociceptors; Opioid Peptides; Pain Measurement; Pain Threshold; Pain, Intractable; Placebos; Receptors, Glutamate; Receptors, Opioid; Thermosensing

Pain in multiple sclerosis (MS) is more common than has previously been believed. About 28% of all MS patients suffer from central pain (CP), a pain that is difficult to treat. In the present study we have investigated the responsiveness of this pain to morphine. Fourteen opioid-free patients (eight woman and six men) with constant, non-fluctuating, long-lasting CP caused by MS were investigated. Placebo (normal saline), morphine and naloxone were given intravenously in a standardized manner. The study design was non-randomized, single blind and placebo controlled. Ten patients experienced less than 50% pain reduction by placebo and less than 50% pain reduction by morphine. Four patients were opioid responders, i.e. had minimal or no effect on pain by placebo, >50% pain reduction after morphine and >25% pain increase after naloxone, given intravenously following morphine. However, this response was obtained after high doses of morphine (43 mg, 47 mg, 50 mg and 25 mg; mean 41 mg). Thus, compared with nociceptive pain, only a minority of the patients with CP due to MS responded to morphine and only at high doses. The present results are in accord with experimental studies indicating that neuropathic pain is poorly responsive but not totally unresponsive to opioids. The results do not support the routine use of strong opioids in MS patients with CP.

Topics: Adult; Aged; Analgesics, Opioid; Central Nervous System; Controlled Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Tolerance; Female; Humans; Injections, Intravenous; Male; Middle Aged; Morphine; Multiple Sclerosis; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Intractable; Single-Blind Method; Sleep Stages; Surveys and Questionnaires; Treatment Failure

Until recently, it is generally considered safe to perform magnetic resonance imaging (MRI) in patients with an intrathecal drug administration system (ITDAS) device. In this study, we presented a case of morphine overdose due to ITDAS malfunction during MRI evaluation for the diagnosis of stroke.. A 58-year-old woman was referred to the emergency department for left-sided hemiparesis and dysarthria. She had undergone ITDAS implantation 4 years ago because of intractable back pain. Her brain MRI examination did not show any abnormalities except an old hemorrhagic infarction in the right basal ganglia. After MRI was performed, her symptoms completely resolved. Approximately 3 h after the MRI scan, the patient showed progressive stuporous consciousness and decreased respiration with decreased peripheral oxygen saturation of 80%. Initial arterial blood gas analysis revealed respiratory acidosis with hypoxia and hypercapnia. We suspected the opioid overdose for her unconciousness, small and sluggish pupils, and slow respiration. The patient regained consciousness within 3 min after the administration of naloxone with severe anxiety and irritability, without any respiratory symptoms or focal neurological deficits. In the pump interrogation and actual reservoir checks performed 6 h after the MRI scan, there was no significant difference between the expected reservoir volume and actual reservoir volume. Follow-up MRI performed to rule out posterior circulation infarction showed no structural lesions. The patient was eventually discharged without further neurologic or functional deterioration, with diagnosis of transient ischemia attack for initial symptoms of focal neurologic deficits.. Although both ex vivo and in vivo studies have provided evidence that ITDAS devices are MRI-compatible, the pump is made of titanium and has ferromagnetic components. Since misdiagnosis of overinfusion could lead to mortality, early awareness of overinfusion of the intrathecal drug is needed to all clinicians in case of performing MRI in ITDAS implanted patients.

Topics: Female; Humans; Magnetic Resonance Imaging; Middle Aged; Morphine; Naloxone; Pain, Intractable; Stroke

For the past few decades membrane zinc metallopeptidases have been identified as important therapeutic targets in the control of pain. In particular, neutral endopeptidase (NEP) has been shown to play critical roles in the metabolism of the endogenous peptides Met- and Leu-enkephalins. In this study, we have evaluated the activity of a new fluorinated peptidase inhibitor NESS002ie in both in vitro and in vivo assays. NESS002ie has been compared to the peptidomimetic compound thiorphan and the previously reported NEP selective thiol inhibitor C20. The metallopeptidases inhibitory activity of NESS002ie was tested in vitro using a highly, sensitive, continuous, fluorometric, enzyme assay. Also, the analgesic propriety of NESS002ie, thiorphan and C20 have been evaluated in vivo, by intraplantar, intravenous and intrathecal administration, through nociception assays based on formalin test in mice. Metallopeptidases assays have shown an inhibitory potency of NESS002ie in the nanomolar range for NEP and angiotensin-converting enzyme (ACE). The new fluorinated inhibitor showed higher analgesic activity and bioavailability compared to thiorphan and C20 when administered by both intravenous and intrathecal injections. More significantly, intrathecal injection of NESS002ie reduced both the first and the second phases of the formalin biphasic pain response. In addition, naltrindole and naloxone reversed the analgesic effect of NESS002ie with a diverse profile. This study shows an improvement in relief of inflammation and pain, in vivo, using NESS002ie compared to reference compounds thiorphan and C20. This significant effect could be due to the replacement of isobutyl chain of the thiol C20 with the trifluoromethyl group.

Topics: Analgesics; Animals; Disease Models, Animal; Formaldehyde; Male; Mice; Naloxone; Pain, Intractable; Protease Inhibitors; Sulfhydryl Compounds; Tyrosine

Chronic use of opioid is associated with pro-nociceptive phenomena such as hyperalgesia or tolerance. The interaction between opioid and non-steroidal anti-inflammatory drugs (NSAIDs) with respect to opioid-associated hyperalgesia and tolerance remains largely unknown. This study examines the effect of subcutaneous or intrathecal administration of ketorolac, an NSAID, on recurrent withdrawal induced hyperalgesia and tolerance to spinal morphine in rats. Animals were infused with morphine intrathecally, and daily subcutaneous naloxone was used for recurrent withdrawal purpose. We observed that escape latencies on hot box were decreased in animals subjected to withdrawal, and this decrease was reversed by subcutaneous ketorolac pretreatment. In addition, we observed that recurrent withdrawal did not significantly affect the magnitude of spinal morphine tolerance. Compared to controls, all morphine infused animals showed similar changes in their dose responses to spinal morphine, effective dose 50 values and tolerance ratios; and these changes were not affected by the ketorolac given subcutaneously. The effect of ketorolac on tolerance was further examined by directly delivering ketorolac to the spinal cord, and again we observed similar changes in the daily latency, percentage of area under the curve and percentage of maximal possible effects among groups infused with morphine, regardless of intrathecal ketorolac treatment. Together, our results demonstrate that recurrent withdrawal is associated with hyperalgesia but this has no effect on the tolerance development; ketorolac protects against recurrent withdrawal induced hyperalgesia without significantly altering spinal morphine tolerance.

Topics: Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Drug Tolerance; Hyperalgesia; Injections, Spinal; Ketorolac; Male; Morphine; Morphine Dependence; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Intractable; Rats; Rats, Sprague-Dawley; Spinal Cord; Substance Withdrawal Syndrome

Chronic pain resulting from metastasis into skeleton of certain neoplastic diseases remains poorly understood and relatively resistant to analgesic treatment. Opioids are the principal axis in drug therapy for this type of pain, especially at the end stage of cancer. Our aim was to examine whether, fentanyl as well as morphine, two potent analgesic opioids commonly used to treat cancer pain, would inhibit pain and bone lesion-related responses in a murine model of bone cancer pain. Repeated administration of equianalgesic doses of fentanyl (0.16 mg/kg s.c. once a day) and morphine (20 mg/kg s.c. once a day) initiated at day 1 (prophylactic treatment) or at day 7 (curative treatment) after tumor cell inoculation in the femoral cavity consistently decreased bone pain symptoms and tumor growth-induced bone destruction (micro-CT bone structure parameters). Both fentanyl and morphine treatments resulted in clear antinociceptive properties as well as reductions in cancer cell-induced bone lesions. The present results demonstrate that fentanyl, and to some lesser degree morphine, has potential benefits in the treatment and development of bone cancer pain. As such, chronic administration of high doses of certain opioids like fentanyl may have clinical utility in the management of bone cancer pain.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; Body Weight; Bone and Bones; Bone Neoplasms; Femur; Fentanyl; Male; Mice; Mice, Inbred C3H; Morphine; Naloxone; Narcotic Antagonists; Neoplasm Transplantation; Osteosarcoma; Pain Measurement; Pain, Intractable; Postural Balance; Tomography, X-Ray Computed; Tumor Cells, Cultured

For optimal neural transplantation using gene engineering, it might be important to control the expression of the transfected gene extrinsically as required. This strategy could be very useful for the treatment of intractable pain that responds to opioids. For this purpose, we established a genetically modified embryonal carcinoma cell line (P19) in which the expression of beta-endorphin (beta-EP) could be controlled by the addition of dexamethasone. To obtain extrinsic control, we transfected the cells with pMAMneo containing mouse MMTV-LTR as a promoter and cDNA of the artificial beta-EP. The upregulation of beta-EP, through the activation of MMTV by the administration of dexamethasone, was confirmed in vitro. Then we transplanted these cells into the subarachonoid space in rats and evaluated the analgesic potential of these cells in vivo by hot plate test and formalin test. In the rats that received beta-EP-producing cells, we observed prominent analgesic effects after the transplantation for a month. The administration of naloxone blocked these effects. Intraperitoneal injection of 100 mg/kg dexamethasone further enhanced these effects by up to two times. These data indicate obvious analgesic effects of the cells after the transplantation and the possible exogenous upregulation of transfected beta-EP gene expression in vivo. The application of this technique might provide a new therapeutic approach to various neurological diseases.

Topics: Animals; Dexamethasone; Embryonal Carcinoma Stem Cells; Genetic Therapy; Male; Naloxone; Neoplastic Stem Cells; Nerve Growth Factor; Pain Measurement; Pain, Intractable; Promoter Regions, Genetic; Rats; Rats, Wistar; RNA, Messenger; Transfection; Tumor Cells, Cultured; Up-Regulation

Topics: Analgesics, Opioid; Humans; Naloxone; Narcotic Antagonists; Pain; Pain, Intractable; Tilidine

We report a patient with acromegaly who had severe, intractable headache unrelated to tumor size which dramatically resolved with the somatostatin analog octreotide. The analgesic effects of octreotide were neither related to significant inhibition of growth hormone nor influenced by naloxone. Our data suggest that octreotide should be considered in patients with intractable headache associated with pituitary adenomas. Mechanisms other than tumor size or interaction with the opioid system, such as non-opioid algesic peptide secretion, may be the explanation for severe head pain in some pituitary adenomas.

Topics: Acromegaly; Adenoma; Adult; Growth Hormone; Headache; Humans; Male; Naloxone; Octreotide; Pain, Intractable; Pituitary Neoplasms; Receptors, Opioid

DADL was administered to a patient who was analgetically tolerant to continuously infused, intrathecal morphine sulfate. DADL restored analgesia without respiratory depression but opiate withdrawal syndrome was not prevented. Somnolence, not responsive to naloxone but completely reversed with morphine, was seen as an idiosyncratic mu receptor opiate withdrawal symptom. Clonidine hydrochloride and decreasing doses of oral morphine were used to successfully treat the withdrawal syndrome, including somnolence. Further research is indicated to verify the findings of this one patient and investigate the efficacy of DADL to provide analgesia for morphine-tolerant patients.

Topics: Aged; Carcinoma; Clonidine; Drug Tolerance; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Humans; Injections, Spinal; Male; Morphine; Naloxone; Pain, Intractable; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, mu; Skull Neoplasms; Spinal Neoplasms; Substance Withdrawal Syndrome; Thyroid Neoplasms

D-phenylalanine, bacitracin and puromycin produce long-lasting, naloxone-reversible analgesia in mice. Analgesic potency parallels potency of these compounds as inhibitors of met-enkephalin degradation by mouse brain enzymes. D-phenylalanine potentiates acupuncture analgesia in mice and humans and has been used to ameliorate a variety of human chronic pain conditions.

Topics: Acupuncture Therapy; Analgesia; Analgesics; Animals; Bacitracin; beta-Endorphin; Brain; Drug Synergism; Endorphins; Enkephalin, Methionine; Humans; Kinetics; Mice; Naloxone; Neprilysin; Pain, Intractable; Phenylalanine; Protease Inhibitors; Puromycin; Stereoisomerism

Neuro-adrenolysis of the pituitary gland by injection of pure alcohol was done to control intractable pain associated with wide-spread cancer, and pituitary functions were measured before and after the injection. Of a series of 46 patients undergoing a total of 57 neuro-adrenolysis of the pituitary gland, 22 (38.6%) of these procedures obtained complete pain relief 22 (38.6%) showed improvement, and the remaining 13 (22.8%) no effect. Hormonal changes of pituitary gland were not same among the cases and there was no correlation between hormonal changes and the occurrence of pain relief. Experimental study was done to investigate the effect of hypophysectomy and intracerebroventricular injection of AVP on pain threshold in rats. The study revealed that hypophysectomy and ventricular injection of AVP dose dependently raised pain threshold and these effects were inhibited by naloxone. These facts suggest that the analgesic effects of hypophysectomy and AVP injection into cerebral ventricle are mediated by beta-endorphin.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Animals; Child; Ethanol; Female; Humans; Hydrocortisone; Male; Middle Aged; Naloxone; Neoplasms; Nerve Block; Pain, Intractable; Pituitary Gland; Rats; Rats, Inbred Strains; Vasopressins

Thirteen adult patients with established thalamic syndrome, resistant to prior analgesic and other therapy, were treated with intravenous infusions of the opiate antagonist, naloxone. A total of twenty treatments were administered with doses of naloxone varying from 4.0-8.0 mgs. Seven patients exhibited beneficial effects with the duration of the resultant pain relief ranging from four days to two and a half years. In these patients, pain and hyperpathia were completely obtunded in six out of seven and partially in one. Side effects of therapy were minimal and of short duration being mainly confined to the cardiovascular system. During therapy all patients had continuous E.C.G. monitoring. In certain ischaemic conditions of the central nervous system, endogenous opioids possibly reduce cerebral blood flow via. inhibition of the locus coeruleus and subsequent release of noradrenaline: hence naloxone by inhibiting the opioids could increase cerebral perfusion pressure. This study has shown the benefit of treating patients with cerebral ischaemic lesions with an opioid antagonist. The rapidity of onset of pain relief in these patients would appear to indicate a mode of action by increasing cerebral perfusion.

Topics: Aged; Analgesics; Female; Humans; Injections, Intravenous; Intracranial Embolism and Thrombosis; Male; Middle Aged; Naloxone; Pain, Intractable; Syndrome; Thalamus

To explore new methods for the control of intractable pain caused by advanced cancer, the analgesic effect of electrical stimulation of the pituitary gland was investigated in 25 patients. The results were compared with a control study and with the effects of alcohol-induced pituitary neuroadenolysis (NALP) in the same patients. The pain score (0: no pain at all, 4: extreme pain) in the control study was 3.88 +/- 0.33. After electrical stimulation of the pituitary gland it was 1.24 +/- 1.61; and after NALP it was 1.0 +/- 1.60. The pain scores after electrical stimulation and NALP were significantly lower (P less than 0.01) than those in the control study; but there was no significant difference when the two were compared with each other. The duration of pain relief following NALP (59.65 +/- 68.72 days) was significantly longer compared with that recorded following electrical stimulation (2.97 +/- 2.58 days). Autopsy examinations of 3 patients who expired from their malignancies revealed that the pain relief was unrelated to the degree of necrosis induced in the pituitary by alcohol. Naloxone administration did not inhibit the analgesic effect of either NALP or electrical stimulation. The advantages and disadvantages of electrical stimulation, the pain relief mechanism activated by this method, and potential clinical applications are also discussed.

Topics: Adult; Aged; Electric Stimulation Therapy; Female; Humans; Hypophysectomy; Hypophysectomy, Chemical; Male; Middle Aged; Naloxone; Neoplasms; Pain, Intractable; Pituitary Gland

The clinical results of electrical stimulation in medial thalamic regions for cancer pain have been correlated with the exact location of the stimulation sites. Five brains were examined by post-mortem histology. Chronic implantation of enamel coated platinum-iridium electrodes for up to 17 months caused relatively mild glial and neuronal reactions and no significant haemorrhage or infarction. The anatomical verifications showed that the electrodes were close to, but not exactly in, the regions defined by the stereotactic coordinates. From the clinico-anatomical correlations it appears that good pain relief can be obtained by electrical stimulation in the periventricular gray region of the posterior thalamus.

Topics: Aged; Electric Stimulation; Electric Stimulation Therapy; Electrodes, Implanted; Female; Humans; Male; Middle Aged; Naloxone; Neoplasms; Pain, Intractable; Stereotaxic Techniques; Thalamus

To investigate the possible role of endogenous opiates in the mediation of analgesia produced by low intensity, high frequency transcutaneous electrical stimulation in the presence of chronic pain, an attempt was made to reverse stimulation-induced analgesia with naloxone. Fifteen patients with chronic pain who were consistently relieved of pain by low intensity, high frequency transcutaneous stimulation were studied. During stimulation at 58 Hz, patients were given double-blind intravenous injections of either naloxone (0.4 or 1.2 mg) or saline. Subjective pain ratings were recorded before stimulation, after stimulation, and after naloxone and saline injections. No reversal of analgesia was seen after naloxone or saline. These results suggest that transcutaneous stimulation at low intensity and high frequency may provide analgesia that is not associated with release of endogenous opiates in patients with chronic pain.

Topics: Adult; Analgesia; Double-Blind Method; Electric Stimulation Therapy; Endorphins; Enkephalins; Female; Humans; Male; Middle Aged; Naloxone; Pain, Intractable

The effect of nitrous oxide and morphine sulphate on chronic pain states in man are compared. The similarity of effect indicate that nitrous oxide acts on the morphine receptor. In all cases where analgesia was produced naloxone reversal occurred. These results provide additional evidence for a dual system hypothesis of pain perception and that nitrous oxide analgesia is mediated by the endogenous opiate system. In the light of these findings, the possibility of using nitrous oxide to replace morphine sulphate as a screening test for deep brain stimulation analgesia is discussed.

Topics: Adult; Chronic Disease; Female; Humans; Male; Morphine; Naloxone; Nitrous Oxide; Pain, Intractable

Topics: Depression, Chemical; Humans; Injections, Intravenous; Morphine; Naloxone; Nociceptors; Pain, Intractable; Reflex; Reflex, Monosynaptic; Spinal Cord

Topics: Animals; Arthritis, Experimental; Endorphins; Enkephalins; Naloxone; Pain, Intractable; Rats; Receptors, Opioid; Spinal Cord

Recently, Mayer (1977) and Adams (1976) proved that both acupuncture and direct electrostimulation of deep encephalic structures produce an analgesic effect releasing a neurotransmitter similar to morphine (endorphine). We have verified this hypothesis, using the transcutaneous electrotherapy in five patients with chronic pain at the back (postherpetic neuralgia in 3, pain cancer in 2). All patients related a certain analgesic effect during electrotherapy, with a reduction in pain of more than 50 per cent. During electroanalgesia we administered Naloxone (an antagonist of morphine). In 3 cases we observed a clear, although short, return of algic symptomatology. At the contrary, in other two patients Naloxone caused briefly a further and clear reduction in the pain.

Topics: Adult; Aged; Analgesia; Electric Stimulation Therapy; Endorphins; Female; Humans; Male; Middle Aged; Naloxone; Pain, Intractable

Topics: Endorphins; Humans; Hypophysectomy; Male; Middle Aged; Naloxone; Neoplasm Metastasis; Pain, Intractable