ALTERATIONS IN RESPONSE TO SOMATIC PAIN ASSOCIATED WITH ANAESTHESIA: XVIII: STUDIES WITH SOME OPIATE ANTAGONISTS

It has been shown that tibial pressure algesimetry can be usedto distinguish between the action of intramuscular pethidine100 mg and a placebo. This method has been applied to studythe effect on pain response of the opiate antagonists, levallorphan,nalorphine and four different doses of pentazocine. The twoformer drugs increased the sensitivity to pain soon after administration,though this effect diminished towards the end of the first hour.Pentazocine, on the other hand, had a demonstrable analgesicaction. The opiate antagonist tacrine did not appear to affectthe analgesic action of morphine 10 mg. None of the antagonistswhen given intravenously had an analgesic action comparableto pethidine though there was a wide scatter in the results.Nalorphine and levallorphan partially neutralized the effectof pethidine given previously. Pentazocine had no such antagonisticeffect. It appears, therefore, that it differs from the otheropiate antagonists studied which are antanalgesic or neutralby all the methods of administration used.     

Effect of opiate analgesia and opioid blockade on urethral mucosal sensitivity threshold

The effect of opiate analgesics (omnopon, pethidine, pentazocine) on the urethral mucosal sensitivity threshold in 37 patients, and of the potent opiate/opioid antagonist naloxone on 10 volunteers is described. Omnopon and pentazocine caused a significant decrease in sensitivity (p less than 0.02) and naloxone caused a significant increase in sensitivity (p less than 0.02). The results confirm a role for the endogenous opioids in modulating urethral sensitivity, and the implications of this are discussed.     

Antinociceptive Response to Nitrous Oxide Is Mediated by Supraspinal Opiate and Spinal alpha sub 2 Adrenergic Receptors in the Rat

Background: Despite nearly 150 years of clinical use, the mechanism(s) of action of nitrous oxide (N2 O) remains in doubt. In some but not all studies the analgesic properties of N2 O can be attenuated by opiate receptor antagonists. The purported mechanism for the opiate antagonistic effect relates to the finding that N2 O increases supraspinal levels of endogenous opiates, although this finding has been disputed. Based on the observations that (1) N2 O promotes the release of catecholamines, including the endogenous alpha sub 2 adrenergic agonist norepinephrine, and (2) that descending noradrenergic inhibitory pathways are activated by opioid analgesics, this study sought to determine whether alpha2 adrenergic receptors are involved in the antinociceptive action of nitrous oxide.

Methods: Institutional approval was obtained for the study. Rats breathed 70% N2 O and 30% Oxygen2 in an enclosed chamber. After a 30-min exposure, significant antinociception was indicated by an increase in the latency response to a noxious stimulus (tail-flick latency). The tail-flick latency was tested in rats exposed to 70% N2 O after either systemic or regional (intrathecal or intracerebroventricular) injections with either competitive (atipamezole; yohimbine) or noncompetitive (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) alpha2 adrenoceptor antagonists, or the opiate receptor antagonist naloxone.

Results: When administered systemically, both the opiate (naloxone) and alpha2 adrenoceptor antagonists (atipamezole, yohimbine, and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) blocked the enhanced tail-flick latency response to N2 O. Naloxone administered intracerebroventricularly, but not intrathecally, blocked the enhanced tail-flick latency response to N2 O. Conversely, atipamezole administered intrathecally, but not intracerebroventricularly, blocked the enhanced tail-flick latency response to N2 O.     

Efficacy of continuous subcutaneous pentazocine infusion for the postoperative analgesia in lower abdominal surgery

BACKGROUND: Continuous subcutaneous infusion (CSI) of analgesics may be an alternative for pain control in patients without an epidural catheter. The aim of this study was to investigate the efficacy of CSI using pentazocine in lower abdominal surgery with inhalation anesthesia or with total intravenous anesthesia. METHODS: One hundred forty-seven patients scheduled for gynecological abdominal surgery were analyzed retrospectively. Anesthesia was induced with propofol and was maintained with propofol infusion or isoflurane-nitrous oxide inhalation. All patients received 30-75 mg of pentazocine before incision. At the end of surgery, CSI of pentazocine was begun at a rate of 0.5 ml x hr(-1) x Given regimen was pentazocine 240-390 mg and droperidol 5 mg with 1% lidocaine, and the total amount of dose was 40 ml. RESULTS: Over 80% of patients were assessed to have effective pain relief and minimum side effects. Patients were classified into two groups by anesthetics during anesthesia; propofol, pentazocine, ketamine group (PPK group, n = 61); nitrous oxide, isoflurane, pentazocine group (GOI group, n=88). There were no differences between the two groups regarding postoperative pain relief, while total dose of pentazocine used during anesthesia were lower in GOI group than PPK group. CONCLUSIONS: In patients undergoing lower abdominal surgery, CSI of pentazocine provided effective postoperative pain relief and effectiveness did not depend on anesthetics during anesthesia.     

Experimental Pain Models Reveal No Sex Differences in Pentazocine Analgesia in Humans

Background: Accumulating evidence suggests that there are sex differences in analgesic responses to opioid agonists. Several studies using an oral surgery pain model have reported more robust analgesia to [kappa]-agonist-antagonists (e.g., pentazocine, nalbuphine, butorphanol) among women than among men. However, evidence of sex differences in [kappa]-agonist-antagonist effects from studies of experimentally induced pain in humans is lacking.

Methods: Therefore, the analgesic effects of intravenous pentazocine (0.5 mg/kg) were determined in healthy women (n = 41) and men (n = 38) using three experimental pain models: heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both pentazocine and saline, which occurred on separate days in counterbalanced order.

Results: Compared with saline, pentazocine produced significant analgesic responses for all pain stimuli. However, no sex differences in pentazocine analgesia emerged. Effect sizes for the sex differences were computed; the magnitude of effects was small, and an equal number of measures showed greater analgesia in men than in women. Also, analgesic responses were not highly correlated across pain modalities, suggesting that different mechanisms may underlie analgesia for disparate types of pain.     

Effects of pentazocine in experimental head injury

In previous studies we demonstrated the adverse effects of ethyl alcohol in murine head injury. Using this model in this study, effects of prior administration of pentazocine (Talwin) on the survival of mice are reported. Swiss Webster mice were randomly divided into one of three groups. Group I (n = 20) received pentazocine and Group II (n = 20, controls) received saline. Groups I and II were then injured under ether anaesthesia by allowing a weight to fall from a height of 15 cm on the cranium. Ten animals received pentazocine and were anaesthetized but had no head trauma (Group III). In Group II, 85% survived 24 h, and in Group I, 35% survived; all mice in Group III survived 24 h (significance: chi 2, p less than 0.005; Group I versus Groups II and III). Pentazocine increases the lethality of murine head injury.     

Effects of nalbuphine, pentazocine and U50488H on gastric emptying and gastrointestinal transit in the rat

We studied the effect of mixed agonist-antagonist opioids (nalbuphine and pentazocine) and a kappa opioid agonist (U50488H) on gastric emptying and gastrointestinal transit, and their interactions with morphine in rats. In each group, nalbuphine (0.01-30 mg kg-1), pentazocine (1-30 mg kg-1), U50488H (1-100 mg kg(-1)1) or saline was injected i.p. at 0 min. Another four groups of rats received morphine 13.4 mg kg-1 (ED75) and one of the following substances: saline, nalbuphine, pentazocine or U50488H. In both groups, at 30 min, radiolabelled saline 1 ml was infused into the stomach; at 1 h, gastric emptying and gastrointestinal transit were calculated by measuring the radioactivity in the gastrointestinal tract. Slopes for dose-response curves were determined. Nalbuphine significantly, but only weakly, delayed gastric emptying (P < 0.0005) and gastrointestinal transit (P < 0.01). Pentazocine markedly inhibited both, whereas U50488H did not significantly inhibit either. The slopes of the dose-response curves for nalbuphine, but not for pentazocine, on both gastric emptying and gastrointestinal transit were significantly less steep than those for morphine. Nalbuphine significantly antagonized the inhibitory effect of morphine on gastric emptying (P = 0.005) and gastrointestinal transit (P = 0.02), whereas pentazocine and U50488H did not. Nalbuphine and pentazocine delay gastric emptying and gastrointestinal transit, possibly by different mechanisms.      

Experimental pain models reveal no sex differences in pentazocine analgesia in humans

BACKGROUND: Accumulating evidence suggests that there are sex differences in analgesic responses to opioid agonists. Several studies using an oral surgery pain model have reported more robust analgesia to kappa-agonist-antagonists (e.g., pentazocine, nalbuphine, butorphanol) among women than among men. However, evidence of sex differences in kappa-agonist-antagonist effects from studies of experimentally induced pain in humans is lacking. METHODS: Therefore, the analgesic effects of intravenous pentazocine (0.5 mg/kg) were determined in healthy women (n = 41) and men (n = 38) using three experimental pain models: heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both pentazocine and saline, which occurred on separate days in counterbalanced order. RESULTS: Compared with saline, pentazocine produced significant analgesic responses for all pain stimuli. However, no sex differences in pentazocine analgesia emerged. Effect sizes for the sex differences were computed; the magnitude of effects was small, and an equal number of measures showed greater analgesia in men than in women. Also, analgesic responses were not highly correlated across pain modalities, suggesting that different mechanisms may underlie analgesia for disparate types of pain. CONCLUSIONS: These findings indicate significant analgesic responses to pentazocine in both men and women across multiple experimental pain assays, and the absence of sex differences contrasts with previous data from the oral surgery model. The most likely explanation for the discrepancy in results is that of differences in the pain assays. These findings are important because they suggest that sex differences in opioid analgesia may be specific to certain types of pain.     

A COMPARISON OF THE CIRCULATORY EFFECTS IN MAN OF THE ANALGESICS FENTANYL, PENTAZOCINE AND PETHIDINE

The cardiovascular responses to five sequential intravenousinjections of pentazocine (5x0.6 mg/kg), fentanyl (5x0.001 mg/kg)and pethidine (5x1.0 mg/kg) were assessed in conscious and anaesthetizedsubjects. In conscious volunteers pentazocine raised the systolicpressure by 30 per cent. Pentazocine and pethidine raised thediastolic pressure by 10 per cent and the heart rate by 15 percent; with pethidine the increases were not sustained but tendedto fluctuate. Fentanyl did not affect the pressure or heartrate. In anaesthetized patients, all three analgesics causeda 20–25 per cent fall in blood pressure and heart rate,fluctuations in pressures occurring in the pentazocine and pethidinegroup. No changes of e.c.g. pattern were observed. Pentazocine,pethidine and fentanyl thus exert different haemodynamic effectsin conscious and anaesthetized subjects. A summary of this paper was presented at the Pain Symposiumheld in Munich, October 17-19, 1969.     

A COMPARISON OF THE RESPIRATORY EFFECTS OF MEPTAZINAOL PENTAZOCINE AND MORPHINE

The respiratory effects of a new strong analgesic, meptazinol,were compared with a placebo and with equianalgesic doses ofmorphine and pentazocine in a double-blind crossover trial inseven healthy volunteers. No significant change in the ventilatoryresponse to rebreathing carbon dioxide was observed after meptazinol100 mg/70 kg or placebo. However, both morphine 10 mg/70 kgand pentazocine 60 mg/70 kg depressed the slope of the ventilatoryresponse ( — 30.0% and —31.6% respectively, P>0.02,averaged over the first 3.5-h period). End-tidal carbon dioxidetension (Pe‘co) while breathing room air increased significantlyfollowing all three drugs. However, the increase in Pe’qo,after meptazinol (0.22 kPa averaged over 3.5 h) was significantlyless than that following morphine (0.40 kPa, P>0.05) andpentazocine (0.59 kPa, P>0.01). While breathing room airwith a resistive inspiratory load of 8 kPa litre₁ s, Pe‘co,again increased significantly (P>0.05) following all threedrugs. The increase in Pe’co after meptazinol was thenthe same as that after morphine (0.51 kPa averaged over 3.5h). The increase following pentazocine (0.80 kPa) was significantlygreater than that after both morphine and meptazional(P>0.02).     

Patient-controlled analgesia. A technical toy or a contribution to the treatment of pain?

PCA (patient-controlled analgesia) was used to treat postoperative pain after general surgery and gynecological operations in a total of 82 patients. In a prospective randomized study, 20 of these patients received pentazocine and 20 were treated with Fentanyl. The bolus quantity for pentazocine was 15 mg in 5 ml NaCl, and that for Fentanyl 0.05 mg in 5 ml NaCl. A maximum of 3 boluses was allowed within 1 h; the refractory period was 5 min. Both drugs were equally suited for the treatment of pain. With pentazocine, an average of 144 micrograms kg-1 min-1 was administered during the first 16 h after the operation; with Fentanyl, the quantity taken was 0.78 microgram kg-1 min-1. The inter- and intraindividual variance in the consumption of analgesics described by other authors was confirmed. The amount of analgesics required ranged between 0.05 and 1.95 mg for Fentanyl and between 15 and 435 mg for pentazocine in a period of 16 h. Three patients did not request an analgesic at all. The average consumption of analgesics constantly decreased in the first few postoperative hours, from 0.28 mg every 4 h after the operation to 0.18 mg every 4 h 16 h later (Fentanyl) and from 55 mg every 4 h after the operation to 31.5 mg every 4 h 16 h later (pentazocine). The majority of patients reported very positive experience with PCA. There were few side effects. Problems arose from the negative attitude of other doctors and the nursing staff, and from some misunderstandings.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison between pentazocine, pethidine and placebo in the treatment of post-anesthetic shivering

BACKGROUND: We have compared the effects of pethidine, pentazocine and placebo in the treatment of post-anesthetic shivering. METHODS: Forty-five patients who shivered after routine surgery were allocated randomly to receive normal saline (n=15), pentazocine 7.5 mg (n=15) or pethidine 17.5 mg (n=15). RESULTS: After 10 min, 13 patients had stopped shivering in the pethidine group, which was significantly more than the incidence in the two other groups (placebo=2; pentazocine=4) (P<0.01). Pentazocine was not significantly different from normal saline in affecting shivering. CONCLUSION: We conclude that pentazocine 7.5 mg was not effective in the treatment of post-anesthetic shivering.     

Naloxone: analeptic action unrelated to opiate receptor antagonism?

The effects on the duration of sleeping time (ST) of the opiate receptor antagonists, naloxone and naltrexone, were determined in rats anesthetized by intraperitoneal injection of ketamine, halothane, or pentobarbital. Intracerebroventricular administration of naloxone shortened the duration of sleeping time induced by all three anesthetic agents in a dose-related manner. Centrally administered naltrexone (240 microgram) and systemically administered naloxone (50 mg/kg) prolonged the duration of pentobarbital sleeping time without altering duration of ketamine or halothane sleeping time. Naltrexone (120 microgram) had no effect on the duration of ST. This study does not support a role for opiate receptor regulation of the duration of sleeping time. The evidence supports the hypothesis that naloxone may govern the duration of narcosis through the activation of an opposing arousal system in the CNS, unrelated to pharmacologic competition for opiate receptors.     

Comparison of Paracetamol and Pentazocine Suppositories for Pain Relief after Tonsillectomy in Adults

The pain-relieving effect of paracetamol 500 mg or pentazocine 50 mg suppositories was studied in 91 voluntary adult patients after tonsillectomy in halothane or enflurane anaesthesia. Both suppositories were studied after both anaesthetics. Thus the patients were randomly allocated to four study groups. At 60 min after administration of coded suppositories, 46-50% of the patients in various groups needed extra analgesic and received pethidine 1 mg/kg i.m. Thereafter, the pain relief was satisfactory in all groups until the end of the observation period (120 min). The incidence of vomiting, the most common side effect, ranged from 5 to 14% in the groups. Bleeding from the operation site was most common (14%) in the patients treated with pentazocine after enflurane anaesthesia and did not occur in the patients treated with pentazocine after halothane anaesthesia. The incidence of bleeding in both paracetamol groups was 9%. In all cases, bleeding stopped without any special treatment. The results suggest that both paracetamol 500 mg and pentazocine 50 mg suppositories in the doses used were weak analgesics for throat pain after tonsillectomy in adults in the early postoperative period. The incidence of side effects was relatively low.     

A comparison of buprenorphine and pentazocine for the relief of postoperative pain

The analgesic potency, efficacy, duration of action and side-effects of buprenorphine (Temgesic) 0.3 mg and 0.6 mg were compared with those of pentazocine (Sosegon) 30 mg and 60 mg in 100 male patients who had undergone orthopaedic surgical procedures. The drugs were given by intramuscular injection 30 minutes before completion of the surgical procedure, and the quality of pain relief and incidence of side-effects were assessed at 30-minute intervals for at least 6 hours. Buprenorphine was shown to be safe, to be more potent and to have a longer duration of action than pentazocine, and to result in less nausea, vomiting and euphoria, but it was associated with a higher incidence of postoperative sedation than pentazocine.     

Postoperative nausea and vomiting after laparoscopic cholecystectomy under total intravenous anesthesia using propofol combined with fentanyl or pentazocine

BACKGROUND: The aim of this study was to compare the incidence of postoperative nausea and vomiting (PONV) in propofol-anesthetized patients receiving either fentanyl or pentazocine as opioid supplement. METHODS: Sixty-seven patients scheduled for laparoscopic cholecystectomy were analyzed retrospectively. Patients were classified into two groups according to opioid supplement under propofol-anesthesia; pentazocine group (n = 26) and fentanyl group (n = 41). Anesthesia was induced with propofol using target controlled infusion method, and was maintained with propofol infusion with pentazocine or fentanyl and intermittent administration of vecuronium with 40% oxygen in air. RESULTS: The incidence of PONV was 23.1% in fentanyl group and 22.0% in pentazocine group, respectively. The incidence of PONV was not different between the groups. There were no severe complications. CONCLUSIONS: The incidence of PONV in propofol-anesthetized patients receiving pentazocine as opioid supplement is not different from that in patients receiving fentanyl.     

Interaction between opiate subtype and alpha-2 adrenergic agonists in suppression of noxiously evoked activity of WDR neurons in the spinal dorsal horn.

Several studies have demonstrated synergistic antinociception following low-dose administration of morphine and alpha-2 adrenergic agonists at the spinal level. This study was carried out in order to identify the opiate subtypes that are likely to be involved in such synergistic suppression of noxiously evoked activity of wide-dynamic-range (WDR) neurons in the dorsal horn of the spinal cord. We also examined the effect of opiate antagonists and alpha-2 adrenergic antagonists on the suppression produced by opiate or alpha-2 adrenergic agonists. Extracellular activity of single WDR neurons in the spinal dorsal horn, which was evoked by a radiant heat stimulus (51 degrees C), was recorded in decerebrate, spinally transected cats. Agonists were administered spinally and antagonists intravenously. In the synergism study, ineffective doses of the moderately selective mu agonist morphine (25 micrograms), the delta agonist DADL (20 micrograms), and the selective delta agonist DPDPE (30 micrograms), when combined with an ineffective dose of the alpha-2 adrenergic agonist clonidine (5 micrograms) produced significant synergistic suppression of noxiously evoked WDR neuronal activity. However, the ineffective or slightly effective dose of the selective mu agonist DAGO (1 or 1.5 micrograms, respectively) did not show any synergistic action with clonidine. Furthermore, the synergism between morphine and clonidine was reversed by the selective delta antagonist ICI 174,864. We interpret these results to indicate that opiates interact at spinal delta receptors to produce a synergistic suppression of evoked WDR neuronal activity in the presence of spinal clonidine. An alternative explanation is that ICI 174,864 may interact in some way with alpha-adrenergic systems.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of subcutaneous patient-controlled analgesia using pentazocine for major abdominal surgery in elderly patients

BACKGROUND: Subcutaneous patient-controlled analgesia (PCA) may be an alternative method for pain control in patients without an epidural catheter. The authors evaluated the efficacy and safety of subcutaneous PCA using pentazocine for postoperative analgesia after major abdominal surgery. METHODS: Sixty-three patients scheduled for major abdominal surgery were analyzed retrospectively. Patients were classified into three groups by age; under 65 years of age (Group 1, n = 23) ; 65-75 years (Group 2, n = 30); over 75 years (Group 3, n = 10). Anesthesia was induced with propofol and was maintained with isoflurane-nitrous oxide inhalation. All patients received 30-45 mg of pentazocine before incision. At the end of surgery, subcutaneous pentazocine PCA was begun at a rate of 0.5 ml x hr(-1). Given regimen was pentazocine 240-390 mg and droperidol 5 mg with 1% lidocaine, and the total amount of dose was 40 ml. Postoperative pain control was assessed using a 5 rating verbal pain score (VPS) and a visual analog pain scale (VAS). RESULTS: Subcutaneous PCA of pentazocine provided adequate analgesia over 70% of the patients studied. There were no differences between the three groups regarding VPS and VAS. There are no severe complications. CONCLUSIONS: Subcutaneous PCA of pentazocine is a simple, safe, and effective method to control postoperative pain after major abdominal surgery. Effectiveness of subcutaneous PCA of pentazocine did not depend on age of patients.     

Dose requirements of pentazocine during abdominal surgery in total intravenous anesthesia using propofol

BACKGROUND: To determine the dose requirements of pentazocine when administered as a single bolus dose in total intravenous anesthesia with propofol for abdominal surgery. METHODS : One hundred and fifty-six patients scheduled for abdominal surgery were analyzed retrospectively. Patients were classified into three groups according to duration of the operation ; under 120 min (Group 1, n=87) ; 120-240 min (Group 2, n=56) ; over 240 min (Group 3, n=13). Anesthesia was induced with propofol using target controlled infusion method, and was maintained with propofol infusion, pentazocine as a single dose before incision, and intermittent administration of vecuronium with 40% oxygen in air. RESULTS: Dosage of pentazocine was significantly increased according to length of the operation. The maintenance doses of propofol were not different among the three groups. Awakening time in about 80% of patients in each group was within 15 minutes. There are no severe complications. CONCLUSIONS : Total intravenous anesthesia with propofol and pentazocine is useful to stabilize hemodynamics and to achieve rapid recovery. For the operation within 120 min, 0.7 mg x kg(-1) of pentazocine is necessary whereas 0.8 mg x kg(-1) of pentazocine is needed in the operation of 120-240 min.     

THE USE OF NARCOTIC ANTAGONISTS IN ANAESTHESIA

The effects of the opiate antagonists are briefly described. A detailed account is then given of the use of these antagonists in pre- and postoperative medication and in anaesthesia. Finally, the value of the antagonists in the treatment of opiate overdosage is discussed.