Effects Of Morphine Sulfate Research Articles

İskemi Reperfüzyon Hasarı Sonrasında Akciğer Dokusunda Meydana Gelen Histopatolojik Değişiklikler Üzerinde Morfifin Sulfatın Etkisi

Amaç: Hücre düzeyinde iskemiye karsı toleransın oluşmasında endojen opioidler önemli rol oynamaktadır. Çalışmamızda akciğerin iskemi-reperfüzyon hasarı sonrasında akciğer dokusunda meydana gelen histopatolojik değişiklikler üzerinde morfin sulfatın etkisini araştırmayı amaçladık. Gereç ve Yöntemler: Çalışmada 40 adet Wistar Albino cinsi dişi sıçan kullanıldı. Denekler 4 gruba ayrıldı. İskemi reperfüzyon (IR) grubunda sol beşinci interkostal aralıktan torakotomi yapılarak iskemi reperfüzyon hasarı oluşturuldu. İskemi reperfüzyon ve ardkoşullama (İschemic postconditioning) (IRAK) grubunda torakotomi, iskemi reperfuzyon ve iskemik ardkoşullama yapıldı. IRAK3 ve IRAK30 gruplarında IRAK grubunda yapılan işlemlere ilave olarak 3μmol ve 30μmol dozlarında morfin sülfat verildi. Akciğer dokusu histopatolojik incelemesinde nötrofil sayısı, konjesyon, interstisyel ödem, doku hasarı, VEGF (Vasküler endotelyal büyüme faktör) ve EGFR (Epitelyal büyüme faktörü reseptörü) ile pozitif boyanan hücreler yarı nicel olarak değerlendirildi. Bulgular: Histopatolojik incelemede IR grubu ile IRAK (P<0.01), IRAK3 (P<0.01) ve IRAK30 (P<0.01) grupları arasında nötrofil sayısı ve konjesyon skoru açısından istatistiksel olarak anlamlı fark saptandı. Doku hasarı skoru açısından IR grubu ile IRAK (P<0.01), IRAK3 (P<0.01) grupları arasında ve IRAK grubu ile IRAK30 (P<0.05) grubu arasında istatistiksel olarak anlamlı fark saptandı. Ayrıca IR grubu ile IRAK3 (P<0.01) , IRAK30 (P<0.01) grupları arasında VEGF (+) ve EGFR (+) boyanan hücre sayısı skoru açısından istatistiksel olarak anlamlı fark saptandı. Sonuç: Sonuç olarak iskemi reperfuzyon periyodunda iskemik ardkoşullama ve morfin sulfat uygulanmasının histopatolojik değerlendirilmesinde, iskemi reperfüzyon hasarının önlenmesinde ard koşullamadan çok morfin sulfat verilmesinin daha etkin bir yöntem olduğu saptanmıştır.

P107 The effect of morphine sulphate on life quality of cancer patients in terminal stage

P107 The effect of morphine sulphate on life quality of cancer patients in terminal stage

Differential modulation of TMJ neurons in superficial laminae of trigeminal subnucleus caudalis/upper cervical cord junction region of male and cycling female rats by morphine

Sex differences in the cellular responses to morphine were examined in an animal model of temporomandibular joint (TMJ) pain. TMJ-responsive neurons were recorded in the superficial laminae at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C 2) junction region, the initial site of synaptic integration for TMJ afferents, in male and cycling female rats under barbiturate anesthesia. Unit activity was evoked by local injection of bradykinin into the TMJ capsule at 30 min intervals and the effects of morphine sulfate (0.03–3 mg/kg, i.v.) were assessed by a cumulative dose regimen. Morphine caused a dose-related inhibition of bradykinin-evoked unit activity in males and diestrous females in a naloxone-reversible manner, while evoked unit activity in proestrous females was not reduced. The apparent sex hormone-related aspect of morphine analgesia was selective for evoked unit activity, since the spontaneous activity of TMJ units was reduced similarly in all groups, while the convergent cutaneous receptive field area of TMJ units did not change in any group. These results were consistent with the hypothesis that sex hormone status interacts with pain control systems to modify neural activity at the level of the Vc/C 2 junction region relevant for TMD pain.

Dextromethorphan, an NMDA-receptor antagonist, enhances the analgesic properties of morphine

Preclinical studies demonstrated that dextromethorphan hydrobromide (DM) blocks tolerance to the analgesic effects of morphine sulfate (MS) and enhances its analgesic effect. The analgesic enhancing properties of DM in combination with MS have been confirmed in a clinical development program in over 2200 patients. MorphiDex® (MS:DM) is a 1:1 (mg to mg) ratio of morphine sulfate and dextromethorphan hydrobromide. Double-blind, single-dose analgesic efficacy studies in over 800 patients with post-surgical pain demonstrate significantly superior analgesic activity for MS:DM (60:60 mg) over both individual components MS 60 mg and DM 60 mg. MS:DM had a rapid onset of pain relief and at least an 8-hour duration of analgesic effect. ___TAGSTART___BR___TAGEND___Double-blind, multiple-dose studies in 321 patients with cancer and other chronic pain demonstrate MS:DM provides satisfactory pain control, but at a significantly lower mean MS daily dose. In a crossover study (2 weeks per treatment, 89 patients), 80.3 mg/day of MS in MorphiDex® capsules provided equal pain control to 161.5 mg/day of MS alone (P < 0.001). Also, the combination had a significantly longer interval between doses (P = 0.05) and a significantly longer interval between last dose of day and first dose next day (P = 0.01). In a 4-week parallel group study in 232 patients, MS:DM demonstrated pain control at least equivalent to MS alone at a significantly lower MS daily dose (P = 0.04). The data show significant dose escalation for MS alone, but not for MS:DM, to maintain satisfactory pain relief over 4 weeks (P = 0.025). Also, significantly more patients preferred double-blind MS:DM to run-in MS than preferred double-blind MS to run-in MS (P = 0.026). In these double-blind studies, the adverse event profile for MS:DM was similar to that for MS. ___TAGSTART___BR___TAGEND___A 2-week open-label study in 457 patients with chronic pain was conducted to provide guidelines in converting patients from other opioid medication to MS:DM. Patients took only 79% of their prestudy MS equivalent dose as MS from MS:DM (P < 0.0001) and a significantly higher percentage of patients rated MS:DM very good or excellent compared to their prestudy opioid (P < 0.0001). Most patients took 3 to 4 doses per day and used no other opioid for breakthrough pain. MorphiDex® provides a new potent analgesic with a novel mechanism of action and a favorable side effect profile for the treatment of moderate to severe cancer pain.

The effects of morphine on responding under variable-interval schedules

The study was designed to integrate rate-related principles and Herrnstein's hyperbolic matching equation (1970) as they apply to drug effects. It was also designed to assess the validity of an interpretation of Herrnstein's equation used to account for the behavioral mechanisms of drug action. Eight rats were trained to press a lever under a range of variable-interval (VI) schedules of reinforcement using sucrose solution (0.1 M) as a reinforcer. After 90 baseline sessions the effect of morphine sulfate, 3, 6, 12 and 17 mg/kg, on responding was tested. Response rates were suppressed in a dose-dependent manner after morphine administration. Herrnstein's equation, which states that responding is a function of relative reinforcement rate, provided a good description of the relationship between responding and reinforcement under most conditions. Therefore, the traditional variable used to predict the drug effect in rate-dependency functions, baseline response rate, was compared to a new variable, baseline relative reinforcement rate. Relative reinforcement rate performed as well as response rate in predicting the drug effect. In order to test if Herrnstein's hyperbola can identify the behavioral mechanisms of the action of morphine, the concentration of the sucrose solution was increased (0.32 M). The y-asymptote of Herrnstein's equation, k, increased as sucrose concentration increased. This calls into question one common interpretation of Herrnstein's equation used to identify the behavioral mechanisms of drug action.

Effect of Morphine Sulfate (MS) on Nitric Oxide End Products and Nitric Oxide Synthase (NOS) Expression in Newborn Piglet Brain Endothelial Cells † 344

Effect of Morphine Sulfate (MS) on Nitric Oxide End Products and Nitric Oxide Synthase (NOS) Expression in Newborn Piglet Brain Endothelial Cells † 344

Central effects of morphine and morphine-6-glucuronide on tissue protein synthesis.

The central and peripheral effects of morphine sulfate (Mor) and morphine-6-glucuronide (M6G) on the fractional rates of tissue protein synthesis (kappa s) were determined. We determined ks in conscious rats 2 h after intracerebroventricular injection of Mor (80 micrograms/rat), M6G (1 microgram/rat), or H2O (5 microliters). Intracerebroventricular Mor and M6G administration decreased ks in the liver by 19 and 18% spleen by 19 and 17%, and gastrocnemius by 18 and 17%, respectively. Intravenous injection of Mor (8 mg/kg) or M6G (0.4 mg/kg) did not affect ks in any of the tissues studied. Intracerebroventricular Mor and M6G resulted in an equivalent 10- to 15-fold increase in plasma epinephrine, 2- to 3-fold increase in norepinephrine, and 80-90% increase in corticosterone, with no change in insulin levels. Intracerebroventricular Mor produced a significant 30% decrease in arterial partial O2 pressure (PaO2) and no significant changes in arterial pH and arterial partial CO2 pressure (PacO2). Intracerebroventricular M6G decreased PaO2 (40%) and pH (from 7.44 +/- 0.01 to 7.34 +/- 0.02) and increased Paco2 (36%). The potential contribution of hypoxia to the opiate-induced decrease in ks was assessed in an additional set of rats exposed to 5% O2-95% N2. One or 2 h of hypoxia decreased protein synthesis in the brain by 47 and 56%, liver by 69 and 69%, and skeletal muscle by 51 and 52%, respectively. Our results indicate that Mor and M6G suppress tissue protein synthesis through central mechanisms, most likely mediated by opiate-induced respiratory depression in association with neural and hormonal alterations.

Is there an opiate receptor in the snail Megalobulimus sanctipauli? Action of morphine and naloxone

The effects of morphine sulfate (10, 15 and 20 mg/kg) or saline control (5 mg/kg) on the latency of the anterior body-lifting response to heat (avoidance response) were determined in four groups of snails Megalobulimus sanctipauli ( n = 6) individually placed on a metal plate mounted on the surface of a water bath at 52 ± 1°C. The effects of pre-treatment with naloxone hydrochloride (5 mg/kg) or saline (2.5 ml/kg) control on the responses to morphine (15 mg/kg) were determined in two different groups of animals ( n = 6). Administration of morphine resulted in an increase in the avoidance behavior latency with maximum effects occuring at 15 mg/kg, 10–15 min after injection. The effects of morphine disappeared within 90–120 min. Saline treatment had no detectable effects on the latency of the response to an aversive stimulus. Naloxone significantly blocked ( P < 0.05, Student paired t-test) the increase in avoidance behavior latency. The present results indicate that: 1. morphine has an antinociceptive effect on the response of Megalobulimus sanctipauli to an aversive thermal stimulus; and 2. the morphine-induced “analgesia” may be caused by the stimulation of μ opiate receptors.

Morphine sulfate, transdermal fentanyl citrate and ketorolac tromethamine: effects on postoperative pulmonary function

The physiological effects of morphine sulfate and fentanyl citrate on postoperative pulmonary function demonstrate varying degrees of respiratory depression related to dose, route of administration and pre-existing pathologies. Current postoperative analgesic therapies that include concomitant use of narcotic agonists and nonsteroidal anti-inflammatory drugs require adjustment of drug dosages to provide adequate pain relief while avoiding drug-induced complications. Specific nursing considerations include understanding therapeutic and adverse effects of these agents on pain and ventilation, continuous pain assessment and early recognition and treatment of respiratory depression.

Effect of high doses of morphine on Con-A induced lymphokine production in vitro

Morphine, a potent analgesic drug as well as the active metabolite derived from heroin, has been reported to affect a variety of immune functions. In vivo administration of high doses of morphine to animals has been shown to inhibit natural killer (NK) cell activity in the rat (Shavit et al., 1984) and splenic T cell mitogenic response in the mouse (Bryant et al., 1988). We report here on the effect of morphine sulfate (MS) (0.2–1.6 mM) on Concanavalin-A (Con-A) stimulated lymphokine production by mouse splenocytes in vitro. Twenty-four hour incubation of mouse splenocytes with MS, removal of the drug and activation with Con-A resulted in a significant (linear regression, P < 0.001) dose-related inhibition of lymphokine production (IC50 = 0.8 mM) as measured by bioassay for interleukin-2 (IL-2)/interleukin-4 (IL-4). The inhibitory effect of MS on lymphokine production was not blocked by opiate antagonists nor was the inhibitory effect mimicked by equivalent concentrations of mu, delta or epsilon receptor-specific opiate agonists. Exposure to the concentrations of MS used did not reduce viability of mouse splenocytes as determined by Trypan Blue exclusion. Morhpine did not inhibit protein synthesis or adenylate cyclase activity in a T cell clone under identical conditions, indicating that MS, in this concentration range, does not simply interfere with all cell functions in a nonspecific manner. These results suggest that (1) morphine directly inhibits splenocyte functions, (2) the inhibitory effect is not mediated through classical opiate receptors, and (3) the inhibitory effect is not due to toxicity.

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The effect of morphine sulfate on the body temperature of the rat has been investigated. With a dose of 10 mg/kg administered intravenously there occurred a marked fall in core temperature and the degree and duration of hypothermia increased to give a maximum response with 35-50 mg/kg. Doses of 1 and 5 mg/kg caused either no change or a rise in temperature. Injection of 50 µg morphine sulfate into the region of the preoptic/anterior hypothalamic nuclei also led to a fall in core temperature, while injections into other regions of the hypothalamus were ineffective. Introduction of the drug into the area of the mammillary nuclei caused hyperactivity and hyperthermia. It is suggested that the hypothermic effect of morphine is due to depression of the set point of the thermoregulatory center in the anterior hypothalamus.

Morphine-Induced Pupillary Fluctuation: Physiological Evidence Against Selective Action on the Edinger-Westphal Nucleus

In the rat, the predominant pupillary effect of morphine sulfate (30 mg/kg, i.p.) is mydriasis, interrupted periodically by miotic excursions. Using infrared video pupillometry, respirometry and EEG recording, we had previously reported that miotic excursions are always correlated with the onset of EEG bursting, while mydriatic excursions are preceded by respiratory slowing and correlated with EEG burst cessation. In the current study, we found that during morphine-induced EEG bursting and related miosis, delivery of an alerting stimulus to the rat caused an immediate conversion sequence composed of respiratory slowing, burst cessation and mydriatic excursion. We also simulated morphine-induced EEG bursting through non-opioid means by delivering kindling electrical stimuli to the amygdala. When the stimulus was given during morphine-induced mydriasis, the stimulus-induced bursting resulted in a miotic excursion identical to spontaneous morphine-induced miotic excursions. These results indicate 1) that the reticular activating system is involved in morphine-induced mydriatic excursions and 2) that EEG bursting is not simply correlated with morphine-induced miotic excursions, but causes them. Collectively, these results strengthen our hypothesis that the Edinger-Westphal nucleus is not the site in which the selective, receptor-mediated pupillary effects of morphine are initiated.

The effects of morphine in the consummatory contrast paradigm.

Rats shifted from 32% to 4% sucrose show a negative contrast effect, licking significantly less than animals that receive only 4% sucrose. The effects of morphine sulfate (0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 mg/kg) on negative contrast were investigated in four experiments. Contrast was reduced on both the 1st and 2nd postshift day by the 4.0 and 8.0 mg/kg doses, but the effects were less robust than those seen with the benzodiazepines. The effects of morphine on contrast were dissociable from simple increases in sucrose consumption. Naloxone (0.25, 0.5, and 1.0 mg/kg) had no effect on contrast or sucrose intake. However, the contrast-reducing effect of morphine (4.0 mg/kg) was blocked by pretreatment with naloxone (0.50 mg/kg). The results are discussed in terms of other anxiolytic screening paradigms that have obtained "partial anxiolytic effects" using morphine.

Opiate receptor mediated hyperthermic responses in rat following Ca++ channel antagonists

The effects of morphine sulfate on rectal temperature and on Ca++-stimulated Mg++ATPase activity in crude synaptosomal fraction (P2) of cortex, hypothalamus and cerebellum were investigated in rat. Morphine (3-15 mg/kg, SC) produced hyperthermia at 30-120 min after the drug administration. The Ca++/Mg++ ATPase activity in hypothalamus and cortex was decreased while there was no change in Mg++ ATPase activity. The enzyme activity in cerebellum was not affected. The opiate antagonist naloxone hydrochloride (5 mg/kg, SC) antagonized the effect of morphine on rectal temperature and Ca++/Mg++ ATPase activity. The effects of different calcium channel antagonists (nimodipine 1 mg/kg, verapamil 2.5 mg/kg and diltiazem 10 mg/kg, SC) on the changes induced by morphine were also investigated. These antagonists not only antagonized morphine hyperthermia, but also the inhibitory effect of morphine on Ca++/Mg++ ATPase activity in hypothalamus. The calcium channel agonist BAY K8644 (3 mg/kg, SC) produced hypothermia and also stimulation of Ca++/Mg++ ATPase activity in hypothalamus. Naloxone failed to alter these effects of BAY K8644. These studies demonstrate that Ca++ transport in hypothalamus, as indicated by Ca++/Mg++ ATPase activity, plays an important role in thermoregulation and thermoregulatory changes induced by opiates.

The effects of morphine on sympathetic transmission in the stellate ganglion of the cat

The aim of this study was to investigate which of the processes involved in synaptic transmission are affected by morphine in concentrations comparable to those used during surgical procedures. The effects of morphine sulfate on ganglionic transmission were studied in the stellate ganglion of the cat using intracellular and extracellular recordings in vitro. The neurons of the stellate ganglion were depolarized using preganglionic nerve stimulation, postganglionic nerve stimulation, and intracellular stimulation before and after introduction of morphine sulfate (up to 20 micrograms/mL). Tissue concentrations of morphine were estimated using radiolabeled morphine. Axonal transmission and the excitability of the postganglionic neurons to direct intracellular stimulation was not affected at the concentrations of morphine studied. In addition, morphine had a dose-dependent depolarizing effect on the resting membrane potential of most of the neurons in the stellate ganglion. Such neuronal depolarizations alone could initially produce excitation in some cell populations, followed by inhibition, secondary to the membrane depolarization, leading to depression of sympathetic nerve activity. The overall ganglionic transmission as recorded using an evoked potential was biphasic. At low doses morphine facilitated transmission, while at larger doses morphine attenuated evoked potentials. These effects do not appear to be mediated through classical opiate receptors since they are not blocked by naloxone.

The effects of morphine sulphate on ovulation in the immature rat treated with PMSG

Two experiments were carried out on the effects on ovulation of morphine sulfate administered prior to the preovulatory LH surge in the immature rat treated with PMSG. At the commencement of the experiments, rats were 30 days old. In Experiment 1 all rats were injected subcutaneously with 12 IU of PMSG at 1200 hr on day 30. Doses of 6, 12, 24 and 36 mg/kg of morphine were given IP at 1555 hr on day 32. Examination of oviducts on the morning of day 33 enabled the verification of ovulation as well as oocyte counts. Results suggest that the effect of morphine on ovulation is biphasic resulting in the stimulation of ovulation at low doses (6 mg/kg) and inhibition of ovulation at high doses (24 and 36 mg/kg). In Experiment 2, rats injected with a low dose of PMSG sufficient to result in ovarian maturation but not in a preovulatory LH surge, were injected on the eve of day 32 with either saline, 6 or 24 mg/kg morphine. The treatment of rats with 6 mg/kg morphine significantly increased mean ovulatory values compared with control and 24 mg/kg morphine conditions. Further, the percentage of 6 mg/kg treated rats ovulating was more than that of both control and 24 mg/kg morphine conditions. The failure of rats treated with 24 mg/kg morphine to display increments in ovulatory response similar to 6 mg/kg morphine injected rats suggests that increased ovulation is not due to the ability of morphine to cause adrenal progesterone release but is more probably the result of LH release at low doses of morphine.

Potentiation of morphine analgesia after pretreatment with probenecid or sulfinpyrazone

Pretreatment with uricosuric agents probenecid or sulfinpyrazone potentiate the analgesic effects of morphine sulfate as ascertained using the phenylquinone (PQ)-induced writhing test. Doses of either uricosuric agent at 50 mg/kg had no effect on the number of PQ-induced writhes in test animals while potentiating the analgesic effects of morphine. High doses of probenecid or sulfinpyrazone alone did produce decreases in PQ-induced writing. Probenecid (50 mg/kg) did not alter hot water tail flick latency nor did it influence morphine analgesia. Attempts to uncover the underlying mechanisms in the uricosuric agent plus morphine attenuation of PQ-induced writhing were directed towards a possible displacement of morphine from plasma binding sites. However, administration of N-methyl-H3-morphine and estimation of plasma and brain morphine concentrations indicate no differences in the uricosuric drug pretreated groups compared to controls. The conflicting results in the PQ writhing test vs. hot water tail flick might indicate a false positive response in the former test. On the other hand this might be indicative of differing analgesic mechanisms for different types of pain. If the latter is true, this drug interaction may prove clinically useful.

Effects of morphine sulphate on pituitary-testicular morphology of rats

Morphine sulphate was administered, by s.c. injection, to male rats at 50 mg/kg/day for up to 9 weeks. Control rats were given s.c. injections of sterile water. Serum luteinising hormone (LH) and testosterone concentrations and the weight and morphology of testes, pituitary glands and secondary sex organs were examined after 4 and 9 weeks' morphine treatment and also 13 weeks after dosing stopped. Treatment with morphine decreased serum LH and testosterone concentrations and reduced secondary sex organ weights. Differential staining techniques revealed modified secretory activity of pituitary gonadotrophic cells. All stages of spermatogenesis were found in testicular sections, but quantitative reductions in spermatogenic cell populations were found among morphine-treated rats. All the observed effects were reversed within 13 weeks of drug withdrawal. These findings are discussed in relation to existing knowledge of the hormonal control of spermatogenesis in rats.

Effects of morphine anesthesia on myocardial contractility, blood flow, and metabolism

Morphine sulfate is an anesthetic that is frequently used in cardiac operations. Because the knowledge regarding the effects of this drug on the hemodynamic status and myocardium is yet to be defined, we undertook a study in which the effects of morphine sulfate and saline (control group) were compared. Fifteen dogs were anesthetized with chloralose and underwent median sternotomy. A 2 mg/kg dose of morphine sulfate was administered intravenously three times—each time at a 30-min interval (morphine group, eight dogs). In the remaining seven dogs, an equal amount of saline was administered intravenously. The following parameters were measured 10 min after each injection: arterial, central venous, left atrial, and left ventricular pressures, arterial and coronary sinus blood gases and lactates, cardiac output, myocardial blood flow (microsphere technique), and myocardial ATP, glycogen and lactate. Cardiac output, mean arterial pressure, left ventricular dp/dt, myocardial blood flow, myocardial lactate, and lactate extraction did not change significantly in the control group. However, in the morphine group, cardiac output decreased from 103 ± 11 ml/kg/min to 43 ± 6 ( P < 0.005), mean arterial blood pressure decreased from 121 ± 7 mm Hg to 76 ± 10 ( P < 0.05), left ventricular dp/dt decreased from 3134 ± 439 mm Hg/sec to 1548 ± 305 ( P < 0.05), and myocardial blood flow fell from 63 ± 5 ml/min/100 g to 47 ± 4 ( P < 0.05), in spite of a reduction in coronary vascular resistance from 1.66 ± 0.14 mm Hg/ml/100 g/min to 0.74 ± 0.17 ( P < 0.01). Myocardial lactate increased in the morphine sulfate group from 3.04 ± 0.50 μmoles/g to 4.80 ± 0.71 ( P < 0.05), and lactate extraction decreased from 0.23 ± 0.06 μmoles/ml to -0.07 ± 0.13 ( P < 0.05). In chloralose-anesthetized animals, anesthetic doses of morphine sulfate decreased left ventricular contractility, cardiac output, and myocardial blood flow, and increased production of lactate by the myocardium. Our study indicates that morphine sulfate is not as safe a cardiac anesthetic as commonly thought.

Effects of morphine sulfate on dorsal-horn neuronal responses to graded noxious thermal stimulation in the decerebrate cat.

Effects of morphine sulfate upon activity of the neurons of dorsal-horn lamina V as evoked by graded noxious thermal stimuli applied on the receptive field were studied in spinal cord-transected, decerebrate cats utilizing an extracellular microelectrode recording technique. All single units studied (n = 30) responded to noxious thermal as well as to noxious mechanical stimulation. Their spontaneous discharge frequency was 9.7 +/- 1.5 (mean +/- 1 SE) impulses/sec (IPS), the threshold skin temperature was 44.8 +/- 0.2 C, and a linear correlation existed between skin temperature and discharge frequency at 6.7 +/- 0.6 IPS/degree C. Morphine, 1 and 2 mg/kg, iv, suppressed spontaneous activity by 53 +/- 6 and 84 +/- 6 per cent, respectively; increased threshold skin temperature to 46.5 +/- 0.3 and 47.9 +/- 0.5 C, respectively, and maintained the linear correlation between skin temperature and discharge frequency but depressed the mean slope of the regression line to 4.5 +/- 0.7 and to 2.4 +/- 0.4 IPS/degree C, respectively. Naloxone, 0.02--0.04 mg/kg, iv, reversed all of these changes produced by morphine. The results of the present study are, to the authors' knowledge, the first demonstration of the suppressive effect of morphine on the spinal nociceptive neurons in Rexed lamina V as they respond to graded noxious thermal stimuli. These results may explain the analgesic action of morphine at the spinal level.