A survey on the intended purposes and perceived utility of preoperative cardiology consultations

N-methyl-D-aspartate (NMDA) antagonists, such as MK801, delay the development of morphine tolerance. Magnesium, a noncompetitive NMDA antagonist, reduces postoperative morphine requirements. The present study was designed to evaluate the effects of intrathecal co-administration of magnesium sulfate with morphine on antinociceptive potentiation, tolerance, and naloxone-induced withdrawal signs. Magnesium sulfate (40-60 microg/h) co-administration for 7 days, similar to MK801 (10 nmol/h), prevented the decline in antinociceptive response compared with morphine (20 nmol/h). Magnesium sulfate (60 microg/h) produced no antinociception, but co-infused with morphine (1 nmol/h), it resulted in potentiated antinociception compared with morphine throughout the 7-day period. Probe morphine doses after 7-day infusions demonstrated a significantly greater 50% effective dose value for morphine 1 nmol/h (109.7 nmol) compared with saline (10.9 nmol), magnesium sulfate 60 microg/h (10.9 nmol), and magnesium sulfate 60 microg/h plus morphine 1 nmol/h (11.2 nmol), which indicates that magnesium had delayed morphine tolerance. Morphine withdrawal signs after naloxone administration were not altered by the co-infusion of magnesium sulfate. Cerebrospinal fluid magnesium levels after intrathecal magnesium sulfate (60 microg/h) for 2 days increased from 17.0 +/- 1.0 microg/mL to 41.4 +/- 23.6 microg/mL, although serum levels were unchanged. This study demonstrates antinociceptive potentiation and delay in the development of morphine tolerance by the intrathecal coinfusion of magnesium sulfate and morphine in the rat. Implications: The addition of magnesium sulfate, an N-methyl-D-aspartate antagonist, to morphine in an intrathecal infusion provided better analgesia than morphine alone in normal rats. These results suggest that intrathecal administration of magnesium sulfate may be a useful adjunct to spinal morphine analgesia.     

Further evidence that nitric oxide modifies acute and chronic morphine actions in mice

The effects of the nitric oxide (NO) synthase inhibitor, N(omega)-nitro-L-arginine (L-NNA, 2.5-10 microg i.c.v.), and the NO synthesis precursor, L-arginine (L-Arg, 2.5-10 microg i.c.v.), on morphine-induced analgesia, and on morphine-induced tolerance and dependence were examined in mice. Administration of L-NNA diminished the morphine-induced analgesia. L-Arg pretreatment increased the analgesic effect of morphine. Repeated pretreatment (three times, at 24-h intervals) with L-NNA diminished both acute and chronic tolerance to morphine, whereas both the acute and the chronic morphine-induced tolerance increased after the repeated (three times, at 24-h intervals) administration of L-Arg. Neither L-NNA nor L-Arg affected the signs of morphine dependence, as assessed by naloxone (1 mg/kg, s.c.)-precipitated withdrawal. Our data suggest that increased NO synthesis potentiates morphine analgesia and enhances the development of morphine tolerance in mice.     

Pain tolerance in hypnotic analgesic and imagination states.

Investigated the effectiveness of hypnotically suggested analgesia and pleasant imagery conditions in modifying the tolerance of an increasingly intense electrical stimulus; attempted to determine the feasibility of increasing analgesic effects by a combination of these conditions (analgesia plus pleasant imagery); and explored the hypothesis that Ss with highest levels of state anxiety would show the largest changes in tolerance. 36 female undergraduates served as Ss. Simulator and hypnosis Ss were tested for pain tolerance under 3 conditions. Simulators had no significant tolerance increases. For hypnosis Ss, the analgesia and the analgesia plus pleasant imagery conditions were both effective in modifying tolerance. The analgesia condition produced the highest tolerance increases. The pleasant imagery condition did not produce a significant group tolerance increase. However, an analysis of imagery content suggested that images which were not body oriented did significantly modify tolerance levels. State anxiety was unrelated to tolerance, but there was a consistent negative correlation between trait anxiety and all tolerance changes for simulator Ss. (45 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Novel qualitative structure-activity relationships for the antinociceptive actions of H2 antagonists, H3 antagonists and derivatives

Recent studies have shown that cimetidine, burimamide and improgan (also known as SKF92374, a cimetidine congener lacking H2 antagonist activity) induce antinociception after intracerebroventricular administration in rodents. Because these substances closely resemble the structure of histamine (a known mediator of some endogenous analgesic responses), yet no role for known histamine receptors has been found in the analgesic actions of these agents, the structure-activity relationships for the antinociceptive effects of 21 compounds chemically related to H2 and H3 antagonists were investigated in this study. Antinociceptive activity was assessed on the hot-plate and tail-flick tests after intracerebroventricular administration in rats. Eleven compounds induced time-dependent (10-min peak) and dose-dependent antinociceptive activity with no observable behavioral impairment. ED50 values, estimated by nonlinear regression, were highly correlated across nociceptive assays (r2 = 0.98, n = 11). Antinociceptive potencies varied more than 6-fold (80-464 nmol), but were not correlated with activity on H1, H2 or H3 receptors. Although highly potent H3 antagonists such as thioperamide lacked antinociceptive activity, homologs of burimamide and thioperamide containing N-aromatic substituents retained H3 antagonist activity and also showed potent, effective analgesia. A literature review of the pharmacology of these agents did not find a basis for their antinociceptive effects. Taken with previous findings, the present results suggest: 1) these compounds act on the brain to activate powerful analgesic responses that are independent of known histamine receptors, 2) the structure-activity profile of these agents is novel and 3) brain-penetrating derivatives of these compounds could be clinically useful analgesics.     

Structural organization and chromosomal localization of the human hepatocyte growth factor activator gene--phylogenetic and functional relationship with blood coagulation factor XII, urokinase, and tissue-type plasminogen activator

BACKGROUND: This study determined the dose-response relation of intrathecal fentanyl for labor analgesia and described the onset, duration, and quality of analgesia when used as the sole analgesic. METHODS: Eighty-four parturients in active labor who requested analgesia were randomized to one of seven treatment groups. They received 5-45 microg intrathecal fentanyl as part of a combined spinal-epidural technique. Visual analog pain scores were recorded before and at intervals after injection patients requested additional analgesia. The occurrence and severity of pruritus, nausea, and vomiting were also recorded. Maternal blood pressure was recorded before injection and at intervals after injection. Fetal heart rate was recorded before and 30 min after injection. RESULTS: By 5 min after injection, pain scores were significantly different among groups (P < 0.001). Mean duration of analgesia increased to 89 min as the dose increased to 25 microg. Maternal diastolic blood pressure was significantly lower 10 and 30 min after injection. There was no difference among groups in the incidence of pruritus; nausea and vomiting were uncommon. Fetal heart rates did not change after injection. A dose-response curve indicates that the median effective dose of intrathecal fentanyl for labor analgesia is 14 microg (95% confidence interval, 13-15 microg). CONCLUSIONS: Intrathecal fentanyl produces rapid, profound labor analgesia with minimal side effects. These data indicate that there is little benefit to increasing the dose beyond 25 microg when it is used as the sole agent for intrathecal labor analgesia.     

Hypnotic analgesia, placebo analgesia, and ischemic pain: The effects of contextual variables.

In two experiments we examined the relation between hypnotic and placebo analgesia using ischemic pain. The first experiment examined an artifact in a previously used ischemic pain stimulus. Experiment 2 investigated the relation between hypnotic and placebo analgesia using a submaximum effort tourniquet technique to produce ischemic pain. High- and low-susceptible subjects received hypnotic and placebo analgesia in counterbalanced order. High-susceptible subjects received placebo analgesia followed on a subsequent trial by hypnotic analgesia showed significant increases in tolerance from placebo to hypnotic analgesia. When presented in the reverse order, however, placebo analgesia and hypnotic analgesia led to equivalent levels of tolerance in both high- and low-susceptible subjects. A similar pattern of findings emerged for subjects' magnitude estimates of pain, but it was not related to hypnotic susceptibility. These findings indicate that both hypnotic and placebo analgesia may be contextually dependent phenomena. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Activation and expression of endogenous pain control mechanisms in rats given repeated nociceptive tests under the influence of naloxone.

In six experiments, it was found that animals administered the opiate receptor blocker naloxone prior to either hot-plate or tail-flick nociceptive tests developed reduced sensitivity to pain relative to animals tested under saline. The naloxone-induced analgesia was most pronounced following administration of 10 mg/kg naloxone, with weaker effects occurring at 0.5 and 2 mg/kg. The effect manifested itself in tests using mild (48.5° hot-plate tests), but not more severe (52° or 56° hot-plate tests), intensities of nociceptive stimulation. The analgesia observed in animals tested under naloxone arose in part from the attenuation of the habituation of stress-induced analgesia produced by the novelty of the test apparatus, and in part from exposure to nociceptive stimulation. It appears to be mediated by a nonopiate mechanism; naloxone enhanced the analgesia produced by exposure to brief, continuous shock, but blocked the analgesia elicited by prolonged, intermittent shock (see Lewis, Cannon, & Liebeskind, 1980). We also found that administration of naloxone prior to nociceptive testing enhanced the development of conditioned autoanalgesia (as assessed by nociceptive tests conducted under saline), and that the enhanced conditioned autoanalgesia summated with the analgesic effect of morphine. The results are discussed in terms of the activation and expression of both opiate and nonopiate pain suppression mechanisms; their implications for models of situation specific morphine analgesic tolerance are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correlation between motility of testicular spermatozoa, testicular histology and the outcome of intracytoplasmic sperm injection

Many studies have demonstrated the postoperative analgesic efficacy of fentanyl delivered i.v. by patient-controlled analgesia (PCA) devices at demand doses ranging from 10 to 50 microg, but none has sought to define the optimal fentanyl PCA dose. In this randomized, double-blind, multicenter study, we compared the safety and efficacy of three administered demand-dose sizes of fentanyl (20, 40, and 60 microg) in 150 patients after major surgery. Efficacy was dose-dependent; positive response rates (i.e., a global assessment score of "very good" or "excellent" and the absence of severe opioid adverse effects) were 42%, 52%, and 68% for the 20, 40, and 60 microg demand-dose groups, respectively, and were significantly higher in the 60 microg demand-dose group. The number of doses administered and missed attempts were significantly smaller in the 40 and 60 microg demand-dose groups compared with the 20 microg demand-dose group. This suggests that the 20 microg demand dose provided inadequate pain relief. Adverse respiratory events were more frequent and mean respiratory rates were significantly slower with the 60 microg demand dose, compared with the 20 or 40 microg demand doses. These results indicate that, of these three doses, the 40 microg demand dose was optimal for fentanyl PCA management of moderate to severe pain after major surgery. IMPLICATIONS: The postoperative analgesic efficacy of fentanyl delivered i.v. by patient-controlled analgesia devices has been demonstrated for demand doses ranging from 10 to 50 microg, but the optimal fentanyl dose remains unknown. In this randomized, double-blind study, we compared three demand dose sizes of fentanyl (20, 40, and 60 microg) and found that the 40 microg demand dose was the most appropriate for fentanyl patient-controlled analgesia management of postoperative pain.     

Shock controllability and the nature of stress-induced analgesia.

Three experiments, with 160 male albino rats, examined the impact of the escapability of shock on the nature of the analgesia produced by shock. In Exp I, Ss were exposed to 0, 20, 40, or 80 escapable or yoked inescapable shocks. Tailflick testing revealed a double-peak pattern in which analgesia was present after 20 and 80 shocks for both escapable and inescapable shock. Analgesia after 20 escapable or inescapable shocks was insensitive to subcutaneous naltrexone (14 mg/kg), as was the analgesia after 80 escapable shocks. However, the analgesia after 80 inescapable shocks was completely blocked by naltrexone. In Exp II, the analgesia following 80 inescapable shocks persisted for at least 2 hrs, whereas it dissipated rapidly following 80 escapable shocks. The analgesia produced by escapable shock even dissipated with the continued occurrence of escapable shock. Shock controllability altered the analgesia produced by subsequent exposure to shock. Prior experience with controllable shock completely blocked the late-appearing naltrexone reversible analgesia; prior experience with uncontrollable shock led it to appear sooner. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of systemic, intracerebral, or intrathecal administration on an N-methyl-D-aspartate receptor antagonist on associative morphine analgesic tolerance and hyperalgesia in rats.

A flavor paired with morphine shifted to the right the function relating morphine dose to tail-flick latencies and provoked hyperalgesic responses when rats were tested in the absence of morphine. These learned increases in nociceptive sensitivity were not mediated by alterations in tail-skin temperature. Microinjection of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP-5) into the lateral ventricle reversed the hyperalgesic responses but spared the tolerance to morphine analgesia. By contrast, systemic administration of the noncompetitive NMDA receptor antagonist MK-801 or intrathecal infusion of AP-5 reversed the hyperalgesic responses as well as the tolerance to morphine analgesia. The results demonstrate that associatively mediated tolerance to morphine analgesia can co-occur with hyperalgesic responses and are discussed relative to learned activation of endogenous pronociceptive mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Randomized comparison of progenitor-cell mobilization using chemotherapy, stem-cell factor, and filgrastim or chemotherapy plus filgrastim alone in patients with ovarian cancer

PURPOSE: This was the first randomized study to investigate the efficacy of peripheral-blood progenitor cell (PBPC) mobilization using stem-cell factor (SCF) in combination with filgrastim (G-CSF) following chemotherapy compared with filgrastim alone following chemotherapy. PATIENTS AND METHODS: Forty-eight patients with ovarian cancer were treated with cyclophosphamide and randomized to receive filgrastim 5 microg/kg alone or filgrastim 5 microg/kg plus SCF. The dose of SCF was cohort-dependent (5, 10, 15, and 20 microg/kg), with 12 patients in each cohort, nine of whom received SCF plus filgrastim and the remaining three patients who received filgrastim alone. On recovery from the WBC nadir, patients underwent a single apheresis. RESULTS: SCF in combination with filgrastim following chemotherapy enhanced the mobilization of progenitor cells compared with that produced by filgrastim alone following chemotherapy. This enhancement was dose-dependent for colony-forming unit-granulocyte-macrophage (CFU-GM), burst-forming unit-erythrocyte (BFU-E), and CD34+ cells in both the peripheral blood and apheresis product. In the apheresis product, threefold to fivefold increases in median CD34+ and progenitor cell yields were obtained in patients treated with SCF 20 microg/kg plus filgrastim compared with yields obtained in patients treated with filgrastim alone. Peripheral blood values of CFU-GM, BFU-E, and CD34+ cells per milliliter remained above defined threshold levels longer with higher doses of SCF. The higher doses of SCF offer a greater window of opportunity in which to perform the apheresis to achieve high yields. CONCLUSION: SCF (15 or 20 microg/kg) in combination with filgrastim following chemotherapy is an effective way of increasing progenitor cell yields compared with filgrastim alone following chemotherapy.     

Dopamine receptor antagonists in the nucleus accumbens attenuate analgesia induced by ventral tegmental area substance P or morphine and by nucleus accumbens amphetamine

In the present study, we examined the effects of dopamine (DA) receptor antagonists infused into the nucleus accumbens septi (NAS) on analgesia induced by intra-ventral tegmental area (VTA) infusions of the substance P (SP) analog, DiMe-C7 or morphine and intra-NAS infusions of amphetamine. Rats received intra-NAS infusions of either the mixed DA receptor antagonist flupenthixol (1.5 or 3.0 microg/0.5 microl/side; DiMe-C7 only), the DA D1/D5 receptor antagonist SCH 23390 (0.1 microg/0.5 microl/side; DiMe-C7 only) or the DA D2-type receptor antagonist raclopride (1.0, 3.0 or 5.0 microg/0.5 microl/side). Ten minutes later, rats received intra-VTA infusions of DiMe-C7 (3.0 microg/0.5 microl/side) or morphine (3.0 microg/0.5 microl/side) or intra-NAS infusions of amphetamine (2.5 microg/0.5 microl/side). Animals were then administered the formalin test for tonic pain. Intra-NAS raclopride prevented analgesia induced by intra-VTA DiMe-C7, intra-VTA morphine and intra-NAS amphetamine. Similarly, intra-NAS flupenthixol or SCH 23390 attenuated the analgesia induced by intra-VTA DiMe-C7. These findings suggest that tonic pain is inhibited, at least in part, by enhanced DA released from terminals of mesolimbic neurons. Furthermore, the evidence that SP and opioids in the VTA mediate stress-induced analgesia suggests that the pain-suppression system involving the activation of mesolimbic DA neurons is naturally triggered by exposure to stress, pain or both.     

Shock-induced analgesia on the formalin test: Effects of shock severity, naloxone, hypophysectomy, and associative variables.

In 5 experiments, 272 female Long-Evans rats were exposed to 3 shocks, spaced 20 sec apart, at 2 levels of severity: low (.75 sec, 1 mA) and high (3 sec, 4 mA). Both shock levels produced a similar suppression of the recuperative behavior elicited by an injection of formalin into the S's hindpaw. Naloxone fully reversed the analgesia produced by the low shock but only partially reversed the analgesia produced by the high shock. Hypophysectomy did not alter the level of analgesia. When the Ss were tested in a chamber different from the one in which they were shocked, both analgesias were totally reversed. However, imposing a delay between shock and analgesia testing did not reduce analgesia. In all experiments, the freezing response was monitored simultaneously with recuperative behavior. A parallel was found between analgesia and this defensive response, suggesting that an animal's endogenous analgesic systems may be activated along with its defensive motivational system. Results point to the critical nature of associative variables in the control of endogenous analgesic systems and suggest that shock severity is a determinant of analgesia's sensitivity to naloxone. (67 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pain-reducing properties of rewarding electrical brain stimulation in the rat.

In 4 experiments with 13 male Charles River rats, electrodes implanted along the medial forebrain bundle were screened for self-stimulation and stimulation-induced analgesia. Analgesia was defined by changes in unconditioned or escape responses to footshock. Almost all electrodes produced both self-stimulation and analgesia or neither. Thresholds for the 2 effects were highly correlated. Brain stimulation produced an analgesic aftereffect comparable in duration with the poststimulation enhancement of performance in self-stimulation (the priming effect). The refractory period of neurons underlying analgesia, assessed by behavioral means, was similar to that previously found for the priming effect in self-stimulation (.8-1.2 msec). Results suggest a common neural system mediating electrical analgesia and the priming effect of self-stimulation. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The estrous cycle and estrogen modulate stress-induced analgesia.

In this article we investigate the impact of estrous cycle, ovariectomy, and estrogen replacement on both opioid and nonopioid stress-induced analgesia. Stage of estrous strongly influenced analgesia. Diestrus females exhibited the typical male pattern produced by the analgesia inducing procedures used—strong nonopioid analgesia following 10–20 tailshocks, and strong opioid analgesia following 80–200 taskshocks. In these experiments the nonopioid analgesia was slightly attenuated during estrus, but the opioid analgesia was markedly reduced. The role of estrogen in producing these changes was studied with estrogen replacement in ovariectomized subjects. Ovariectomy only slightly altered nonopioid analgesia but eliminated opioid analgesia, which suggests that some estrogen might be necessary to maintain the integrity of the system(s) underlying opioid analgesia. Estrogen administration restored opioid analgesia, but further estrogen suppressed opioid analgesia, duplicating the estrus pattern. It did not suppress nonopioid analgesia. Opioid analgesia was enhanced 102 hr after estrogen replacement, thus duplicating the diestrus pattern. Estrogen thus appears to be responsible for the impact of estrous cycle on opioid but not on nonopioid analgesia. These results suggest that ovarian hormones may modulate the impact of stressors on endogenous pain inhibition and other stress-responsive systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adrenalectomy for a solitary adrenal metastasis from lung cancer

Intrathecal sufentanil provides approximately 2 h of excellent labor analgesia with minimal motor blockade. Epidural sufentanil has received less scrutiny but may provide the same benefits as intrathecal sufentanil. In this study, we compared epidural sufentanil 40 microg after a lidocaine with an epinephrine test dose with intrathecal (i.t.) sufentanil 10 microg with respect to onset and duration of analgesia, degree of motor block, side effect profile, and mode of delivery. Seventy ASA physical status I or II parturients in early labor (< or = 4 cm cervical dilation) were randomized to receive either i.t. sufentanil 10 microg with a combined spinal-epidural technique (CSE) or epidural sufentanil 40 microg (e.p.) after epidural catheter placement and testing with 3 mL of 1.5% lidocaine with epinephrine (15 microg). After the administration of analgesia, pain scores and side effects were recorded for each patient at 5, 10, 15, 20, and 30 min, and every 30 min thereafter, by an observer blinded to the technique used. The study period was completed when the patients requested additional analgesia. All patients, except one, achieved adequate analgesia with the initial study dose and satisfactorily completed the study. There were no demographic differences between the two groups. Pain relief was rapid for all patients; pain scores were significantly lower at 5 and 10 min in the i.t. group versus the e.p. group. The mean duration of analgesia was similar between the e.p. group (127 +/- 40 min) and the i.t. group (110 +/- 48 min). No patient experienced any motor block. Side effects were similar between the two groups, except for pruritus-both the incidence and severity were significantly more profound at 5, 10, 15, 20, and 30 min in the i.t. group. There was no difference in time from analgesic to delivery, incidence of operative or assisted delivery, or cervical dilation at the time of redose. For early laboring patients, epidural sufentanil 40 microg after a lidocaine test dose provides analgesia comparable to that of i.t. sufentanil 10 microg with less pruritus. Implications: We compared the efficacy and side effects of intrathecal sufentanil with epidural sufentanil with a local anesthetic test dose for analgesia during labor. Analgesia was equally good, although the intrathecal group experienced more itching.     

Increases in protein kinase C gamma immunoreactivity in the spinal cord of rats associated with tolerance to the analgesic effects of morphine

Our previous studies have indicated a critical role of protein kinase C (PKC) in intracellular mechanisms of tolerance to morphine analgesia. In the present experiments, we examined (1) the cellular distribution of a PKC isoform (PKC gamma) in the spinal cord dorsal horn of rats associated with morphine tolerance by utilizing an immunocytochemical method and (2) the effects of the N-methyl-D-aspartate receptor antagonist MK-801 on tolerance-associated PKC gamma changes. In association with the development of tolerance to morphine analgesia induced by once daily intrathecal administration of 10 micrograms morphine for eight days, PKC gamma immunoreactivity was clearly increased in the spinal cord dorsal horn of these same rats. Within the spinal cord dorsal horn of morphine tolerant rats, there were significantly more PKC gamma immunostained neurons in laminae I-II than in laminae III-IV and V-VI. Such PKC gamma immunostaining was observed primarily in neuronal somata indicating a postsynaptic site of PKC gamma increases. Moreover, both the development of morphine tolerance and the increase in PKC gamma immunoreactivity were prevented by co-administration of morphine with 10 nmol MK-801 between Day 2 and Day 7 of the eight day treatment schedule. In contrast, PKC gamma immunoreactivity was not increased in rats receiving a single i.t. administration of 10 micrograms morphine on Day 8, nor did repeated treatment with 10 nmol MK-801 alone change baseline levels of PKC gamma immunoreactivity. These results provide further evidence for the involvement of PKC in NMDA receptor-mediated mechanisms of morphine tolerance.     

Oxidized collagen stimulates proliferation of vascular smooth muscle cells

We have examined the use of presurgical morphine-midazolam combination in 80 children aged 2-10 y undergoing repair of hypospadias. They were allocated randomly, in a double-blind study, to receive one of four morphine-midazolam combination doses (n = 20 each); (group I: 75 microg/kg each) [corrected] (group II: 75 microg/kg [corrected] morphine, 50 microg/kg [corrected] midazolam); (group III: 50 microg/kg [corrected] morphine, 75 microg/kg [corrected] midazolam); (group IV: 50 microg/kg [corrected] each). Drugs were given after induction of anesthesia and before the start of surgery. Observational scoring system, using crying, movement, agitation, posture and localization of pain as scoring criteria, was used to assess the children during their stay in the recovery room together with their sedative and/or analgesic requirement. Pre-surgical morphine-midazolam administration produced stable hemodynamic variables with satisfactory postoperative analgesia suggesting 75 microg/kg [corrected] dose of both morphine and midazolam as upper permissible dose, and 50 microg/kg [corrected] each as lower effective dose.     

Mutagenesis of Phe381 and Phe382 in the extracellular domain of the insulin receptor: effects on receptor biosynthesis, processing, and ligand-dependent internalization

Subcutaneous injection of formalin produces a biphasic profile of pain response: a transient early phase followed by a tonic late phase. A number of studies have indicated that the development of the late phase of formalin pain is dependent upon prolonged changes in central neural function produced by neural activity that is generated during the early phase (i.e. central sensitization). In support of this, the present demonstrates that stimulation- or morphine-produced analgesia derived from the periaqueductal grey (PAG) during the early phase prevents the development of the phase. These results suggest that descending mechanisms of pain inhibition, as reflected by PAG stimulation- and morphine-produced analgesia, can prevent the development of central neural plasticity following injury.     

Environmentally induced analgesia: Age-related decline in a neurally mediated, nonopioid system.

Two experiments examined the function of an endogenous system of pain inhibition during aging. In Exp I, 80 male Sprague-Dawley rats (aged 3, 14, and 24 mo) were exposed to 90 sec of hindpaw shock. To investigate the pharmacology and anatomy involved in the production of hindpaw shock-induced analgesia, the effects of naltrexone (7 mg/kg), scopolamine (5 mg/kg), and adrenalectomy were examined. Results show that there was an age-related reduction in the degree of analgesia produced by hindpaw shock. Naltrexone and adrenalectomy did not alter the analgesia elicited by hindpaw shock. Scopolamine reduced the analgesia produced by hindpaw shock, and the effectiveness of scopolamine blockage declined with age. Exp II, with 18 3-mo-old and 13 23-mo-old male Sprague-Dawley rats, demonstrated that the effect of scopolamine was specific to the analgesia induced by hindpaw shock because scopolamine was ineffective in modifying the analgesia produced by a different stressor (cold water). It is suggested that the decline in hindpaw shock-induced analgesia is the result of an alteration in the function of the cholinergic system. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)