Elevated plasma vasopressin and normal cerebrospinal fluid angiotensin-converting enzyme in chronic pain disorder.

The study was performed proceeding from the hypothesis that pain proneness in chronic pain disorder (CPD) is a result of alterations in central mechanisms regulating pain sensations. To elucidate the function of the central renin-angiotensin system, the levels of angiotensin-converting enzyme (ACE) and arginine vasopressin (AVP) in cerebrospinal fluid (CSF) and peripheral blood were measured in 15 CPD patients and 19 healthy controls. Plasma AVP levels (p = .01) as well as the serum osmolality (p = .01) were significantly higher in the CPD group. No significant differences in CSF ACE levels were found. AVP is a stress-related peptide, but central antinociceptive effects have also been reported. Elevated plasma AVP levels possibly may constitute a response to chronic stress.

Neuropeptide FF-like immunoreactivity in human cerebrospinal fluid of chronic pain patients and healthy controls.

Neuropeptide FF (NPFF) is a neuropeptide with some antiopioid characters found in several mammalian species. In human brain it might be an important pain-regulating peptide. Using a specific and sensitive radioimmunoassay we found a mean concentration of NPFF in human cerebrospinal fluid (CSF) of healthy volunteers of 1.6 +/- 1.1 pg/ml (n = 19) and in chronic pain (CPD) patients of 1.4 +/- 1.2 pg/ml (n = 16). The NPFF concentrations in CSF and plasma did not correlate. There was no difference in the NPFF concentrations in CSF and plasma between CPD patients and healthy controls. NPFF in CPD patients did not correlate significally with any pain characteristic. This study provides evidence for the presence of NPFF in human brain, but does not support the hypothesis that chronic pain is a consequence of elevated production of NPFF.

Effect of spiritual healing on chronic idiopathic pain: a medical and psychological study.

OBJECTIVE: To study over a period of one and a half years the effect of spiritual healing on patients with idiopathic pain syndrome using several psychological and medical parameters. DESIGN: Randomized clinical trial. SETTING: Outpatient pain clinic. PATIENTS: Twenty-four patients with idiopathic chronic pain who had passed a pretreatment psychological interview were allocated randomly to receive spiritual healing or no active treatment. MAIN OUTCOME MEASURES: Medical interview (Visual Analog Scale and Pain Clinic Investigation Formula); International Association for the Study of Pain (IASP) Data Base Outline; psychological interview (Hopkin's Symptom Checklist, Middlesex Hospital Questionnaire, Beck's Depression Inventory, Coping Strategy Questionnaire, Health Locus of Control scale). Patients were evaluated at baseline and at 2 weeks posttreatment. Final assessment at 1 year posttreatment was done with a modified form of IASP Data Base Outline. RESULTS: There was a minor decrease in analgesic drug intake and an improvement in sleep patterns in patients treated by the healer. Generally, clinical variables remained unchanged. Attitudes toward spiritual healing improved. There was a decrease in the feeling of hopelessness (p < 0.05) and an increased acceptance of psychological factors as reasons for pain (p < 0.05). Other scores of the psychological tests were unaffected by the healing. However, half (n = 6) of the treated patients felt that spiritual healing gave them some relief. CONCLUSION: Spiritual healing appears harmless and was subjectively helpful to some patients suffering from idiopathic chronic pain syndrome.

Antagonism of fentanyl with naloxone during N2O+O2+ halothane anaesthesia.

To investigate the antagonistic effect of naloxone on fentanyl-induced respiratory depression, 55 patients (randomly divided into various study and control groups were studied during nitrous-oxide-oxygen-halothane anaesthesia. Respiratory depression after 0.1 mg of fentanyl was totally reversed by 10 microgram/kg of naloxone, measured as 100% restoration of spontaneous respiration, normal minute volume and end-tidal CO2, while 15 microgram/kg of naloxone was needed to antagonize 0.2 mg of fentanyl. The respective control groups remained apnoeic. If no fentanyl had previously been administered, there was no difference in the respiratory behaviour of naloxone-treated and control patients, which indicates that no unspecific analeptic effect of naloxone could be demonstrated. The circulatory changes after fentanyl were nearly reversed by naloxone, as has been found earlier with other narcotics. Recovery from anaesthesia was scored from 0 to 10 (using a modification of Apgar scores for newborns), and somewhat higher mean scores were obtained with the naloxone-treated patients than with their controls. However, higher postoperative pain scores were recorded in these patients as well as a higher incidence of nausea and vomiting. The study demonstrates the dose-relationships of fetanyl and naloxone for estimation of total antagonism; however, the use of naloxone for partial antagonism at the termination of anaesthesia cannot be based on these findings.

Naloxone as narcotic antagonist after balanced anaesthesia.

Different modes of naloxone administration were studied in 100 patients following N2O-O2-relaxant anaesthesia, where fentanyl was administered for analgesia according to a standardized dose schedule (mean 4.3 microgram/kg/h). After reversal of muscular relaxation, the patients were randomly given naloxone--either 1.0 or 2.5 microgram/kg i.v. or 2.5 or 5.0 microgram/kg i.m., or none (control). Each group consisted of 20 patients. Awakening was fastest after 2.5 microgram/kg i.v. of naloxone (1.8 +/- 0.1 min), the time being significantly shorter (P less than 0.025) than in the control group (2.7 +/- 0.4 min). After 15 min, the minute volume and frequency of respiration were significantly higher (P less than 0.05) in all naloxone groups than in the control group. However, the arterialized venous PCO2 did not show significant differences during the recovery. It is therefore suggested that naloxone reversal may cause an increase in CO2 production. The immediate postoperative pain (score 0-3) was mildest in the control group (1.0 mean) and severest after 2.5 microgram/kg i.v. of naloxone (1.8 mean); the difference was statistically significant (P less than 0.05). The groups receiving 1.0 microgram/kg i.v. and 2.5 microgram/kg i.m. did not differ from each other (1.2 mean). Nausea and vomiting were reported more often after 5.0 microgram/kg im. of naloxone than in other groups. After moderate doses of fentanyl during balanced anaesthesia, routine use of naloxone does not seem to be necessary, but if rapid recovery is essential, 1.0 microgram/kg i.v. or 2.5 microgram/kg i.m. of naloxone may be recommended and these doses do not cause a higher incidence of side effects.

Opioid treatment for radiating cancer pain: oral administration vs. epidural techniques.

In order to determine the optimal pain treatment for patients with cancer involvement of the brachial or lumbar nerve plexuses, a prospective comparative study was carried out using peroral opioid therapy (SO), epidural opioid by a conventional tunnelled epidural catheter (CE) or an epidural catheter connected to an implanted injection port (Port). Pain relief, measured by a visual analog scale (VAS), was similar and adequate in every group already after the first 24 h. CNS side-effects were less frequent and the Karnofsky performance grades slightly superior in the epidural groups. Occlusion and catheter disconnection complicated the pain therapy of five epidural port patients. Epidural dislocation occurred three times in the conventional epidural group. One local infection in the CE group and two in the Port group were recorded. However, no signs of epidural infection were seen at autopsy. The results suggest that due to a lower incidence of side-effects, epidural catheter techniques are superior to peroral opioid in treating pain in these patients. However, complete pain relief was not achieved in all patients, suggesting neurogenic, non-nociceptive pain components. Both epidural techniques seem suitable for long-term pain therapy. Technical improvements are needed in the epidural catheter and the port. The long-term epidural catheter does not seem to cause any major changes in the histology of the dura mater or the connective tissue of the epidural space.

Hyperpotassemia during massive blood transfusions.

Eleven of 21 patients having received more than 10 units of whole blood developed hyperpotassemia during the rapid phase of transfusion. The increase in serum potassium from initial values correlated well (r = 0.74) with the rate of the transfusion. Three of the hyperpotassemic patients developed cardiac arrest but no life-threatening arrhythmias were registered in the normokalemic patients. In contrast to most previous studies, transient hyperpotassemia often necessitating aggressive therapy was quite common in our massively transfused patients.

Restlessness and shivering after naloxone reversal of fentanyl-supplemented anaesthesia.

To study the significance of normalization of ventilatory or thermal homeostasis during naloxone reversal, 95 patients were given naloxone after thiopental-N2O-O2-relaxant anaesthesia supplemented with fentanyl (6 microgram/kg/h). If naloxone 0.16 mg was given to combat postoperative apnoea during hypercapnia (end tidal carbon dioxide concentration (ETco2)8%), minute ventilation and respiratory rate were significantly higher during the first minutes as compared to the normocapnic patients. Shivering occurred in 44% in the hypercapnic group, as compared to about 30% if naloxone was given during normocapnia (ETco2 5%). Postoperative pain and restlessness were significantly increased in the hypercapnic group. During normocapnia, untoward reactions were less frequent (40%) if naloxone was given in smaller increments (0.08 + 0.08 mg) rather than in one dose (0.16 mg) (72%). This was mainly due to nausea (8% compared to 32%). The incidence and severity of shivering showed a positive correlation to the duration of anaesthesia (r = 0.42) and to the total amount of fentanyl (r = 0.32), but not to the actual postoperative oesophageal temperature (r = -0.13). The results indicate that though untoward reactions after naloxone reversal are aggravated by naloxone-induced normalization of deranged homeostatic mechanisms, their aetiology probably should be sought in an acute abstinence syndrome.

Mild analgesics in postoperative pain.

1 The intensity of postoperative pain is influenced by many factors, for example, individual variation, site of incision and type of operation, anaesthetic technique, and the interval from the end of operation to the appearance of pain. 2 These factors affect the efficacy of analgesics. 3 Mild analgesics provide adequate pain relief in half of our patients in the immediate postoperative phase when the pain is slight to moderate. 4 The maximum effect of mild analgesics corresponds to that produced by morphine 6-10 mg. Adequate analgesia may not therefore be provided for the treatment of severe postoperative pain unless narcotic analgesics have been used peroperatively. 5 When mild analgesics are combined with narcotics synergism is achieved. 6 As postoperative pain decreases with time, mild analgesics usually provide adequate pain relief on the first and following postoperative days.

Double-blind, multiple-dose comparison of buprenorphine and morphine in postoperative pain.

The analgesic profile and side-effects of buprenorphine 0.3 mg and morphine 10 mg intramuscularly were compared postoperatively in a double-blind, non-crossover, multiple-dose study. When the patient complained of moderate to severe postoperative pain after halothane-relaxant anesthesia for upper abdominal surgery, the first test dose of either drug was given. Subsequent similar doses of buprenorphine 0.3 mg or morphine 10 mg were given when required (maximum ten doses). The first dose of both drugs gave an equal decrease in pain intensity, suggesting a relative potency of 33:1 for both buprenorphine/morphine. A mean of 0.51 mg buprenorphine or 17 mg morphine had to be administered for satisfactory initial analgesia. Thereafter, the next analgesic dose was required a mean of 10.3 h after buprenorphine compared to 5.9 h after morphine (P less than 0.01). Significantly (P less than 0.01) fewer analgesic doses (mean 5.6) were needed in the buprenorphine group within the first 48 h postoperatively as compared to the morphine group (mean 7.3). A more pronounced mean decrease in the respiratory rate was observed after buprenorphine, but the mean minimum respiratory rates did not differ significantly from each other. Other effects of the two drugs on vital signs were similar. The incidence of other side-effects was fairly similar after both analgesics. The patients' subjective appraisal favoured buprenorphine.

The need for fentanyl supplementation of N2O-O2 relaxant anaesthesia in chronic alcoholics.

In order to find out how the need for analgesic supplementation during N2O-O2-relaxant anaesthesia is affected by chronic alcohol consumption, 82 patients with various known alcohol habits were anaesthetized for gastric or biliary surgery. Muscular relaxation was kept constant with the aid of a peripheral neurostimulator, and fentanyl was given in increments of 0.05-0.1 mg for nociceptive symptoms during the anaesthesia. For induction, alcoholics (annual consumption above 151 pure alcohol) needed significantly more thiopental/kg body weight than social drinkers (1--151 annually) or non-alcoholics (less than 11 annually), and excitative symptoms were more frequent in alcoholics. A positive correlation was found between fentanyl supplementation and alcohol consumption (r = 0.41), non-alcoholics requiring on average 3.8 microng/kg/h of fentanyl, as compared with 6.4 microng/kg/h in alcoholics. This correlation was clearer than that found previously under similar conditions by the authors between halothane supplementation and alcohol consumption (r = 0.20). In both studies the correlation was partly due to the higher incidence of gastric surgery among alcoholics, since gastric surgery itself requires more supplementation. An analysis of the different symptoms pointing to the need for fentanyl supplementation revealed that the simultaneous occurrence of several symptoms and the prevalence of motor responses were more common in alcoholics. In one patient halothane had to be used as well. In other patients no special difficulties were observed, and none of the patients reported dreams or recollections. The results suggest that during N2O-O2-relaxant anaesthesia the demand for fentanyl supplementation is increased by about 70% in chronic alcoholics with a mean annual consumption of 311 pure alcohol.

Respiratory depressant action of tilidine during N2O + O2 anaesthesia.

The respiratory depressant actions of pethidine and tilidine during anaesthesia were compared in 18 surgical patients anaesthetized with N2O + O2 after thiopental induction. Five minutes after thiopental, 0.5 mg/kg pethidine or 1.5 mg/kg tilidine were each given intravenously to six patients, the remaining six patients serving as controls. Minute ventilation, respiratory rate, end-tidal CO2 and PCO2 from arterialized venous blood were measured up to 30 min. Pethidine caused the following maximal changes: V -0.98 +/- 0.24 (s.e. mean) 1/min, rate -5.5 +/- 0.7/min, CO2ET + 0.7 +/- 0.1 vol % and PCO2 + 5.7 +/- 1.1 mm Hg. These changes occurred within 10 min of the injection.

The interaction of tilidine and pethidine in postoperative pain.

The mode of interaction between the new, non-narcotic analgesic tilidine and pethidine was studied in the treatment of postoperative pain. The potency ratio 3:1 (pethidine:tilidine) found previously was used in the comparison. Thus 0.25 mg/kg of pethidine with 0.75 mg/kg of tilidine and 0.5 mg/kg of pethidine with 1.5 mg/kg of tilidine were compared with 0.5 mg/kg and with 1.0 mg/kg of pethidine. These drug combinations proved to be equipotent with the pethidine dosages used. Consequently the mode of interaction seemed to be additive synergism. The onset of action was slightly faster with pethidine, but the duration of action was longer with pethidine-tilidine combinations. Respiratory depression and sedation were less evident after pethidine-tilidine combinations than after equianalgesic doses of pethidine. Circulatory effects were similar in all groups. No statistical difference in other side effects could be demonstrated between the groups.

The need for halothane supplementation of N2O-O2-relaxant anaesthesia in chronic alcoholics.

The demand for intermittant halothane supplementation during N2O-O2-relaxant anaesthesia was studied in 25 alcohlics (annual consumption over 15 1 pure alcohol) scheduled for biliary or gastric surgery. The controls were 45 non-alcoholics and 43 patients with an annual consumption of between 1 to 15 1. Thiopental (3 mg/kg/min) was given for induction. After intubation, halothane supplementation was given in 0.5% concentration for 10-min periods. Standardized criteria for halothane supplementation were various motor and autonomic responses to painful stimuli. Muscular relaxation was kept fairly constant (roughly 90%), as assessed visually with the aid of a peripheral nerve stimulator. The total time for which halothane supplementation was given, expressed as a percentage of the total anaesthesia time, was used as an indication of the need for halothane supplementation. The need for thiopental for induction was not increased to a statistically significant extent in alcoholics, but signs of excitation did occur in 40% as compared with 11% in non-alcoholics (P less than 0.01). The demand for halothane supplementation was higher in alcoholics (47 +/- 4.8%, s.e. mean) than in non-alcoholics (33 +/- 2.3%). This difference, however, was partly due to the higher incidence of gastric surgery, which required more supplementation than biliary surgery. Analysis of the different criteria indicating the need for halothane supplementation revealed that an increase in blood pressure or heart rate was more common in non-alcoholics, whereas motor irritability, sweating and lacrimation were more frequent in alcoholics. Management of the anaesthetic posed no special difficulties in the alcoholics with an estimated mean annual consumption of 32 +/- 4 (s.e. mean) litres of absolute alcohol. Three patients (5% of the alcohol consumers) reported dreams or recollections, suggesting that this mode of halothane supplementation does not guarantee an adequate anaesthetic depth. The difficulties and biases associated with this type of analysis are discussed.

Comparison of the analgesic effects of intravenous nalbuphine and pentazocine in patients with postoperative pain.

One hundred patients, who were in pain during the immediate postoperative period after upper abdominal operations, were included in this double-blind, between-patient, two-dose study. During N2O-O2-halothane-relaxant anaesthesia no analgesics were given. The patients received 0.07 mg/kg or 0.14 mg/kg of nalbuphine or 0.3 mg/kg or 0.6 mg/kg of pentazocine by intravenous injection. Pain and side effects were assessed for 4 h after administration of the test drug, or until the pain returned to the pre-injection level, when a conventional analgesic was given. The onset of pain relief was similar and the peak effect occurred about half an hour after the injection after both drugs. On a milligram basis, nalbuphine seemed to be about three times as potent as pentazocine. The duration of action seemed to be slightly longer after nalbuphine, but 2 1/2 hrs. after the injection the pain had returned to preinjection level in 2/3 of the patients, even after the higher doses of both drugs. Except for sleepiness, there were few side effects and they were similar after both drugs. No psychotomimetic effects were observed.

[Herpes zoster neuralgia--a persistent therapeutic problem]. / Herpes zosterneuralgi--ett envist terapeutiskt problem.

Most patients with acute herpes zoster (AHN) who are younger than 50 yrs recover spontaneously and need no more specific medication than NSAID-analgetics. However, older patients and those treated with immunosuppressive medication are at high risk of developing postherpetic neuralgy (PHN), and may need intensive treatment for severe pain. Unfortunately there is no specific method so far to prevent PHN. In the prevention of PHN some promising results have been gained with antiviral drugs, sympathetic blocks, corticosteroids, psychotropic and anticonvulsive drugs. The earlier any of these treatments is started in AHM, the better results. When PHN has developed, in most cases there is no effective treatment to be offered. In the Pain Clinic of Helsinki University Hospital antidepressive and neuroleptic drugs as well as transcutaneous neurostimulation have been used for PHN treatment.