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The effects of spinally administered R(−)N6-(2-phenylisopropyl) adenosine (R-PIA) on spinal dorsal horn neurons were investigated in anesthetized rats. Extracellular, single-unit recordings were measured during noxious heating of receptive fields on the hind paw. Three series of experiments were carried out to characterize the effects of R-PIA on spinal dorsal horn neuronal activity. In the first set of experiments, R-PIA dose-dependently suppressed noxiously evoked activity of spinal dorsal horn neurons. In the second set of experiments, R-PIA suppressed noxiously evoked activity in neurons sensitized by the topical application of mustard oil to a region of skin adjacent to their receptive fields. In the third set of experiments, R-PIA prevented mustard oil induced sensitization of dorsal horn neurons. In all cases, the adenosine receptor antagonist theophylline reversed the action of R-PIA. The results of these investigations indicate the involvement of spinal adenosine receptors in spinal pathways of central sensitization and in the modulation of somatically induced noxious pain.

Visceral pain, especially that associated with inflammation of visceral organs, is poorly understood and difficult to treat clinically. The purpose of this study was to investigate the effects of intrathecal 2-amino-5-phosphonovaleric acid (AP5, a competitive NMDA antagonist) upon a visceromotor response to distension of colonic tissue inflamed by exposure to turpentine. All experiments were conducted under pentobarbital anesthesia. Animals were prepared with a laminectomy from T12 to L1 to facilitate intrathecal drug administration. Colonic distension thresholds for a visceromotor response were determined in the presence and absence of AP5. Animals were divided into two groups. The NS group received 50 microl of saline intrathecally and the AP5 group 10 mM of AP5 in 50 microl saline. After baseline measurements, intrathecal drugs were administered. Five minutes later, the effects of intrathecal drugs were measured, then 1 ml of 25% turpentine was administered anorectally. Subsequent measurements were made every 5 minutes for the next 90 minutes. Visceromotor thresholds to colorectal distension (CRD) were significantly decreased 50 min after turpentine administration in the NS group. There was no threshold change in the AP5 group. This study suggests that the administration of the competitive NMDA receptor antagonist AP5 in this model blocks the effect of turpentine sensitization on visceromotor response to CRD. The absence of AP5 effects in animals not sensitized by turpentine suggests that NMDA systems may be involved in the sensitization.

The purpose of this study was to compare the effects of intravenously administered morphine on electrophysiological and behavioral responses to colorectal distension (CRD) and to examine the influence of noxious stimuli applied to another part of the body (a laminectomy) on the visceromotor response to CRD. The effects of morphine (0.1–6.4 mg·kg−1) were examined in rate anesthetized with pentobarbital. Electrophysiological (n=16) and behavioral experiments (n=47) were done. Electrophysiological experiments were conducted to examine the effects of morphine on the responses of visceral dorsal horn neurons to CRD; behavioral studies were conducted to compare the effects of morphine with and without a laminectomy (intact group:n=24; laminectomy group:n=23). Morphine suppressed the evoked activities of the visceral dorsal horn neurons in a dose-dependent manner. Similar suppression of the behavioral visceromotor response was observed. Visceromotor thresholds were significantly lower in the intact group than in the laminectomy group during the control study. When morphine was administered, the visceromotor thresholds in both groups increased to a similar level. Behavioral and neurophysiological responses to CRD were suppressed in a similar fashion by morphine. Although laminectomy affected the threshold values of CRD for visceromotor responses, the laminectomy per se plays an insignificant role when adequate morphine is administered.

Background Visceral sensations are an important component of many clinical pain states. It is apparent that intrathecal pain relief may be more effective if appropriate combinations of drugs rather than a single agent can be used. The purpose of this study was to examine the relative contribution of opioid receptor subtypes to visceral antinociception using colorectal distension as a visceral pain model. Methods The minimum colorectal distending pressure necessary to evoke a visceromotor response (contraction of abdominal musculature) was determined before and after the administration of opioid agonists for the mu (morphine), delta ([D-Pen2, D-Pen5] enkephalin [DPDPE]), and kappa (U50,488H) opioid receptors. In addition to the three drugs administered intrathecally, U50, 488H was also administered intravenously. Results Morphine and DPDPE produced a reversible increase in threshold for activation of the visceromotor response (50% maximum possible effect [MPE] at intrathecal doses of 2.2 and 16.4 micrograms, respectively). The maximum intrathecal dose of U50,488H (100 micrograms) produced only a 20% MPE. Intravenous U50,488H produced a 50% MPE at a dose of 2.6 mg/kg. Conclusions The results suggest that spinal mu- and delta- but not kappa-opioid receptors have a significant role in the modulation of visceral nociception induced by colorectal distension. In addition, the results indicate that activation of nonspinal kappa receptors may mediate visceral antinociception.

Background Visceral pain is an important component of many clinical pain states. The perispinal administration of drug combinations rather than a single agent may reduce side effects while maximizing analgesic effectiveness. The purpose of this study was to examine the nature of interactions between an alpha 2-adrenergic agonist (clonidine) and a mu-opioid agonist (morphine), a delta-opioid agonist ([D-Pen2, D-Pen5] enkephalin [DPDPE]), or a kappa-opioid agonist (U50,488H). Methods Colorectal distension was used to elicit a nociceptive visceromotor response (contraction of abdominal musculature) in rats. The ability of intrathecally administered clonidine alone or in combination with morphine, DPDPE, or U50,488H to alter thresholds for the production of the visceromotor response was examined. Results Clonidine produced dose-dependent reduction in threshold. U50,488H, at the doses tested, showed no synergistic interaction with clonidine. Conclusions Spinal combinations of alpha 2-adrenergic and mu- or delta- but not kappa-opioid agonists may be beneficial in the control of visceral pain.

Epidural endoscopy is a minimally invasive technology that is now in active clinical trials. This new technique allows the operator to visualize directly the epidural space and contiguous structures, thus allowing for detailed examination leading to a better understanding of the role of epidural adhesion in the development of sciatica.

The present study examined interactions between mu and delta opiate subtypes and serotonin. Noxious activity evoked by radiant heat (51 degrees C, 8 sec) was extracellularly recorded from single discriminated wide dynamic range (WDR) neurons in decerebrate spinally transected cats. DAGO (mu selective opioid agonist) 1 microgram or DPDPE (delta selective opioid agonist) 30 micrograms was combined with serotonin (n = 6 each) 250 micrograms. The dose of each drug by itself when administered intrathecally produced no suppression of noxiously evoked activity. Although the combination of DAGO and serotonin produced no significant suppression of noxiously evoked activity, DPDPE and serotonin produced significant suppression to 72.8 +/- 8.0 % (mean +/- SEM) of control values (P0.01). Intravenously administered naloxone 0.1 mg reversed the suppression produced by the DPDPE-serotonin combination. Our results suggest that combinations of serotonin and delta selective opiates may be more effective in suppressing noxiously evoked activity than combinations with mu selective opiates.

Behavioral experiments and neurophysiological experiments, the two major types of preclinical studies which have paved the way for the development of spinal analgesia were compared under identical conditions utilizing the same animals. The results demonstrate that the activation of the wide dynamic range (WDR) neurons preceded the behavioral withdrawal reflexes, and that the activation of the WDR neurons occurred at lower stimulus temperature than that for the withdrawal reflex. The results suggest that the neuronal activation began before the behavioral reflex but also that the firing frequency of the WDR neurons at the time of the withdrawal reflex could not distinguish between non-noxious and noxious stimuli. Further study is needed to elucidate the neuronal mechanisms of the activation of the behavioral reflex.

The present study examined whether sphenopalatine ganglion block (SPGB) causes a reduction in the response to acute nociceptive input that may account for the SPGB-induced relief reported by many patients with chronic pain.In a double-blind, crossover design, 16 healthy volunteers underwent separate 15-minute submaximal effort tourniquet tests before and after SPGB with 20% lidocaine plus 1:100,000 epinephrine (SPGBlidocaine) or placebo (SPGBsaline). Responses during each minute of tourniquet inflation were converted to a 1 to 16 scale and classified as nothing (1), mild sensation (2-4), strong sensation (5-7), slightly painful (8-10), definitely painful (11-13), and severely painful (14-16).Maximum pain scores reached 12.6 +/- 2.5 (mean +/- SD) pre-SPGB, 10.9 +/- 3.5 after SPGBsaline, and 11.1 +/- 2.5 after SPGBlidocaine. No significant differences were noted between SPGBlidocaine and SPGBsaline at any of the 15 time points (p = NS by repeated measures ANOVA and paired t-test). However, retrospective grouping of time points noted that scores after SPGBlidocaine were lower in the "strong sensation" range.SPGB does not lessen acute extremity pain to a significant degree and is not in and of itself an effective means of analgesia for acute pain. Its potential impact on nociceptive stimuli that elicit a "strong sensation" (i.e., a score of 5-7 in the present study) should be evaluated in hyperpathic pain states and in states with exaggerated aversive responses.

Pain has been a major concern of humankind since the ancient times, and it remains one of the most important subjects of all health care professionals. Despite the obvious overwhelming clinical importance, the major advances in its diagnosis and therapy have been made only recently. "How do the sensory apparatus of the body and system of signal transmission relate to pain of peripheral origin?" is the topic of discussion. To do this, it is important to understand what constitutes the total pain experience. It consists of: 1) signal transduction at the peripheral receptor site, 2) signal conduction along the peripheral nerve, 3) pain modulation at the level of the spinal cord, 4) pain perception at the supraspinal site, and 5) the associated sensations, emotional reactions, and effective state. The signal transmission related to pain may be modified by various analgesic agents. Specific analgesic agent has a specific site of action which may be at peripheral receptors, at peripheral nerves, at the level of the spinal cord, at supraspinal levels by activating descending inhibitory systems, or at more cephalad levels by reducing the affective component of pain.

Morphine has been considered to be primarily a mu opiate receptor agonist. The present study was designed to determine if opiate receptor subtypes in addition to mu contribute to morphine analgesia at the level of the spinal cord. Extracellular activity of single wide dynamic range (WDR) neurons in the feline lumbar spinal cord were studied. Intrathecal administration of DAGO (selective mu agonist) or DPDPE (selective delta agonist) suppressed the noxiously (51 degrees C radiant heat) evoked activity of WDR neurons. Pretreatment with spinal beta-FNA (selective mu antagonist) antagonized the suppressive effects of spinal DAGO, but not that of DPDPE. Two doses of spinal morphine (200 and 400 micrograms) suppressed the noxiously evoked activity of WDR neurons confirming our previous report. Following beta-FNA pretreatment, the suppressive effects of morphine were reduced, however, when ICI 174,864 (selective delta antagonist) was co-administered with morphine on the spinal cord of the animals pretreated by beta-FNA, there was an even greater reduction in the neuronal suppression by morphine. Intravenous ICI 174,864 also reversed the suppressive effects of morphine in beta-FNA pretreated animals. beta-FNA antagonism of spinal morphine is evidence of the well-known mu receptor-mediating antinociception. However, antagonism by ICI 174,864 of morphine suppression in beta-FNA-pretreated animals demonstrates that morphine is capable of suppressing noxiously evoked activity of WDR neurons as a result of an interaction with delta receptors in addition to mu receptors at the level of spinal cord.

The effect of epidural morphine on the duration of action of epidural 2-chloroprocaine was studied in a double-blind fashion in 30 patients following elective Caesarean section. When compared to epidural saline controls (n = 15), patients (n = 15) who received epidural morphine (4.0-5.0 mg) did not experience a prolongation or reduction in the duration of the somatic or sympathetic nervous system blockades produced by epidural 2-chloroprocaine.

The present study examined the influence of spinally administered fentanyl on the spontaneous and noxiously evoked activity of wide dynamic range (WDR) neurons in the dorsal horn of decerebrate, spinal cord-transected cats. This work was performed in order to evaluate the dose-response relationship, time course, and naloxone reversibility of fentanyl suppression of neurons that are involved with the transmission of information about pain. Extracellular single neuron recordings were obtained from 18 WDR neurons in the lumbar enlargement. These neurons were activated by a radiant heat stimulus on the footpads of the hindpaw. Fentanyl (10, 15, 25 micrograms in 0.5 ml of physiologic saline) was placed on the spinal cord following control studies of each neuron and the effect was observed. In 12 cats, 31 min after fentanyl administration, naloxone (0.1 mg) was administered intravenously, and its effect on the fentanyl suppression was determined. All three doses of fentanyl suppressed both the spontaneous and evoked activity of all the neurons studied. Thirty minutes after fentanyl the mean evoked activity was reduced to 47, 23, and 11% of control values by 10, 15, and 25 micrograms, respectively. The spontaneous activity was reduced to similar levels. Intravenous naloxone (0.1 mg) caused a significant reversal of the fentanyl suppression. The results of the present study indicate that fentanyl causes a naloxone-reversible, dose-dependent suppression of noxiously evoked WDR neuron activity. Such results support the concept that fentanyl is acting through a specific drug-receptor interaction. The onset of neuronal suppression occurred more rapidly, and the duration of the suppression was longer following fentanyl than that seen following spinal morphine. The onset and duration of this suppression correlates well with human clinical data, providing further evidence that alterations of WDR neuronal activity may be important in the production of spinal opioid analgesia.

Morphine sulfate exerts its analgesic action in part through suppression of the activity of spinal cord nociceptive neurons. Cells in Rexed lamina VII are considered to be the cells of origin of the spinothalamic and spinoreticular tracts concerned with nociception. Using graded radiant heat to their peripheral receptive fields, the relationship between the intensity of heat (millicalories per square centimeter per second) which produces noxious stimuli and the response frequency of single units in Rexed lamina VII of the spinal cord was analyzed with extracellular microelectrode recording techniques in 15 decerebrated and spinal-transected cats before and after administration of morphine sulfate (1 mg/kg, iv). A linear relationship between the intensity of heat and the frequency of response discharge was observed (above threshold) both in the control study and after the administration of morphine. Morphine sulfate significantly suppressed the spontaneous activity of the units studied, raised the threshold of their evoked activity to varying intensities of heat, and diminished the slope of the heat intensity vs evoked single-unit response relationship. Naloxone (0.02 mg/kg, iv) eliminated all changes brought about by morphine sulfate.

Four volunteers judged eight levels of thermal stimuli induced by a Hardy dolorimeter, varying in intensity from extremely painful to a low level seldom even perceived. Half of the 406 stimuli were applied during acupuncture and half either before insertion or after removal of the needles. The experimental design minimized or eliminated factors other than the needles themselves, i.e., no medication was given, the subjects were scientists accustomed to objectivity and, on a preceding day or days, all had become experienced in assigning numbers (individually chosen) to the sensations produced by the different stimuli. Galvanic skin resistance was also tested. The results did not show any influence of acupuncture on perception of pain or on galvanic skin resistance.

Alpha-chloralose, an anesthetic agent widely used in neurophysiologic studies, caused a significant and long-lasting suppression of single neuron activity recorded from two areas of the central nervous system in decerebrate cats. A 50 mg/kg dose (an average anesthetic dose used in many neurophysiologic studies) caused suppression of spontaneous and evoked activity of neurons in the dorsal horn of the spinal cord and greater suppression of neurons in the nucleus reticularis gigantocellularis (NRGC) of the medial medullary reticular formation. Many researchers are of the opinion that alpha-chloralose causes less suppression of the central nervous system (CNS) than other commonly used anesthetic agents. The neuronal suppression recorded in this study appears similar in many ways to suppression caused by other anesthetic agents in the same two areas of the CNS. The results of the present study suggest that alpha-chloralose may be capable of producing significant suppression of neurons in the dorsal horn of the spinal cord and NRGC. Its ability to influence other areas of the CNS should not be inferred from these results, but the data do indicate the importance of evaluating the effects of anesthetics upon neurophysiologic systems under study.

The effects of intravenous administration of fentanyl (50 and 100 micrograms/kg) on the discharge activity of the medullary inspiratory neurons and of the phrenic nerve were studied following vagotomy in nine decerebrate, paralyzed mechanically ventilated cats. In six cats, the inspiratory neurons explored were in the dorsal respiratory group (DRG) associated with the nucleus of the tractus solitarius (NTS), while in the remaining three, they were in the ventral respiratory group (VRG). In the former group, the rhythmic discharge of the inspiratory neurons was disrupted by fentanyl and replaced by a continuous discharge superimposed with irregularly occurring bursts. These changes were also reflected by the phrenic nerve discharge. Inspiratory neuronal activity increased significantly (P less than 0.05) at 1 and 5 min after completion of fentanyl injection. Disruption of the rhythmic activity of the inspiratory neurons and its replacement by a continuous and irregular discharge may lead to sustained contraction of inspiratory muscles and cessation of respiration. In the VRG, the activity of the inspiratory neurons was totally abolished by fentanyl. Thus, it appears that different groups of medullary inspiratory neurons have differential sensitivity to fentanyl. Nalbuphine, an opiate agonist-antagonist, restored the normal pattern and magnitude of the activity of the inspiratory neurons.

The effect of halothane on the electrical activity of inspiratory neurons of the nucleus tractus solitarius (NTS) was studied in decerebrate, paralyzed, mechanically ventilated cats. Simultaneous recording of the activity of the neurons of the NTS and the phrenic nerve was done to identify the inspiratory neurons. Cells whose firing activity was synchronous with that of the phrenic nerve were considered inspiratory neurons. Administration of 1% and 1.5% halothane in oxygen induced a dose-dependent depression of the cell activity (spikes/s) with the cervical vagi intact or severed. Five and ten minutes after inhalation of 1% halothane, the cell activity (mean +/- SE) expressed as per cent of the control was 55.3 +/- 9 and 27 +/- 7, respectively (P less than 0.001), before bilateral cervical vagotomy. The corresponding values for 1.5% halothane were 25 +/- 10.1 and 5.6 +/- 3, respectively. Upon termination of halothane administration, the cell activity gradually returned toward the control level. The cell response to halothane was not affected by bilateral cervical vagotomy. Hypercapnia produced by inhalation of 5% CO2 increased the cell activity, but halothane caused profound depression of the cells even in the presence of hypercapnia. Based on these results, it may be concluded that: halothane has inhibitory effects on the activity of the inspiratory neurons of the NTS; and halothane-induced respiratory depression has a central component and that the NTS may serve as a site of action of halothane for its respiratory depressant effect.

The ability of sufentanil to suppress noxiously evoked activity of wide dynamic range (WDR) neurons was studied in decerebrate, spinal-cord-transected cats. Sufentanil, 2.5 micrograms (n = 7) or 5.0 micrograms (n = 7), when administered spinally, produced a significant, dose-dependent suppression of noxiously evoked (51 degrees C radiant heat stimulus) activity of WDR neurons in the dorsal horn of the spinal cord. Spontaneous recovery from sufentanil suppression was not seen for up to 2 h. Reversal following intravenous naloxone, 0.12 mg, although present, was not as complete as that seen following other spinal opiates. Intravenous sufentanil, 5.0 micrograms/kg (n = 4), produced significant but short-lasting depression of noxiously evoked WDR neuron activity. A comparison of the results of this study with data from a previous fentanyl study suggests that sufentanil may be more appropriate than fentanyl for spinal or epidural administration because of a possible longer duration of action. However, the lesser degree of naloxone reversal seen in this study may suggest that, clinically, reversal of sufentanil effects may be more difficult.

The direct application of preservative-free morphine sulfate (1.5%, 1 ml, 19.8 mumol) or fentanyl (0.06%, 1 ml, 1.07 mumol) on the superficial radial or saphenous nerve of cats did not alter the response of single C polymodal nociceptive fibers (PMNs) to noxious radiant heat stimulation of their peripheral receptive fields. Intravenous administration of fentanyl (100 or 200 micrograms/kg, 0.179 or 0.358 mumol/kg) also showed a similar lack of effect on the radiant heat evoked responses of single PMNs. Slight changes in the mean latencies following drug administration were recognized, which were not statistically significant. The use of morphine (1.5%, 1 ml, 19.8 mumol) with preservatives (chlorbutanol 0.5% and sodium bisulfite less than 0.1%) caused conduction block of PMNs within 6-15 min. Subsequent washout of the drug resulted in the return of the unitary discharges within 8 min. Lidocaine (0.25 and 0.5%, 10.7 mumol and 21.4 mumol) caused conduction block within 5-18 min. These data support the classically held concept that opiates, in clinically useful concentrations, do not alter peripheral nerve function.

The effects of halothane and sodium thiopental on dorsal horn cell unit activity were studied in the lumbar spinal cord of decerebrate, low thoracic spinal cats. Both halothane (0.5, 1 and 1.5%) and sodium thiopental (2.5, 5 and 10 mg/kg) depressed, in a dose-dependent manner, the spontaneous firing frequency of cells in Rexed laminae I, V and VI and the evoked firing frequency of cells in laminae I and V. They, however, had no effect on cells in lamina IV. The maximum depression of cell activity occurred 5 to 8 minutes after inhalation of halothane and 2 to 3 minutes after the intravenous administration of sodium thiopental. The recovery of cell activity occurred within 15 to 30 minutes after discontinuation of halothane and within 10 to 30 minutes after intravenous administration of sodium thiopental. The depressive effect of halothane and sodium thiopental, both primarily hypnotic anesthetics, on lamina VI cells is in contrast to our previous finding that morphine sulfate, nitrous oxide and ketamine hydrochloride, primarily analgesic agents, had no significant effect on this lamina.

Four volunteers judged eight levels of thermal stimuli induced by a Hardy dolorimeter, varying in intensity from extremely painful to a low level seldom even perceived. Half of the 406 stimuli were applied during acupuncture and half either before the insertion or after removal of the needles. The experimental design minimized or eliminated factors other than the needles themselves; i.e. no medications were given; the subjects were scientists accustomed to objectivity and, on a preceeding day or days, all became experienced in assigning a number (individually chosen) to the sensation produced by the different stimuli. Galvanic skin resistance was also tested. The results did not show any influence of acupuncture on pain perception or galvanic skin resistance.

The distribution of intrathecally administered 3H-morphine was examined by light microscopic autoradiography in rat spinal cord and temporal changes in silver grain localization were compared with results obtained from simultaneous measurements of analgesia. After tissue processing, radio-activity was found to have penetrated in superficial as well as in deeper layers (Rexed lamina V, VII, and X) of rat spinal cord within minutes after application. Silver grain density reached maximal values at 30 min in every region of cord studied. Radioactivity decreased rapidly between 30 min and 2 hr and then more slowly over the next 24 hr. In rats tested for responses to a thermal stimulus (tail flick test), intrathecal administration of morphine (5 and 15 micrograms) resulted in significant dose dependent analgesia that peaked at 30 min and lasted up to 5 hr (P less than 0.5). There was a close relationship between analgesia and spinal cord silver grain density during the first 4 hr of the study. It is postulated that the onset of spinal morphine analgesia depends on appearance of molecules at sites of action followed by the activation of anti-nociceptive mechanisms.

The effect of halothane on the electrical activity of inspiratory neurons of the nucleus tractus solitarius (NTS) was studied in decerebrate, paralyzed, mechanically ventilated cats. Simultaneous recording of the activity of the neurons of the NTS and the phrenic nerve was done to identify the inspiratory neurons. Cells whose firing activity was synchronous with that of the phrenic nerve were considered inspiratory neurons. Administration of 1% and 1.5% halothane in oxygen induced a dose-dependent depression of the cell activity (spikes/s) with the cervical vagi intact or severed. Five and ten minutes after inhalation of 1% halothane, the cell activity (mean +/- SE) expressed as per cent of the control was 55.3 +/- 9 and 27 +/- 7, respectively (P less than 0.001), before bilateral cervical vagotomy. The corresponding values for 1.5% halothane were 25 +/- 10.1 and 5.6 +/- 3, respectively. Upon termination of halothane administration, the cell activity gradually returned toward the control level. The cell response to halothane was not affected by bilateral cervical vagotomy. Hypercapnia produced by inhalation of 5% CO2 increased the cell activity, but halothane caused profound depression of the cells even in the presence of hypercapnia. Based on these results, it may be concluded that: halothane has inhibitory effects on the activity of the inspiratory neurons of the NTS; and halothane-induced respiratory depression has a central component and that the NTS may serve as a site of action of halothane for its respiratory depressant effect.

The purpose of this study was to examine the effects of alfentanil applied to the surface of the spinal cord and the effects of intravenously administered alfentanil on noxiously evoked activity of dorsal horn neurons. Extracellular single neuron recordings were obtained from wide dynamic range neurons in 26 decerebrate cats with transected spinal cords. Spinally administered alfentanil, 25 micrograms or 50 micrograms, caused 36 and 86% suppression of noxiously evoked activity, respectively. Maximum mean suppression was achieved at 24 and 21 min after 25 micrograms, and 50 micrograms, respectively. Intravenous naloxone, 0.1 mg, when tested, completely reversed the suppression. Spontaneous recovery to control values occurred within 2 hr. Intravenously administered alfentanil, 12.5 micrograms/kg or 25 micrograms/kg, produced suppression of 43 and 89%, respectively, with maximum mean suppression observed at the 6- and 3-min time points, respectively. Complete recovery after intravenous administration was seen within 30 min. This study, using a sensitive neurophysiologic assay, demonstrates the important differences in onset and duration of drug effects that must be considered when comparing the responses of spinal cord neurons to intravenously administered narcotics and narcotics applied directly to the surface of the spinal cord.

This study was designed to determine if spinally administered epinephrine is capable of suppressing noxiously evoked activity of wide dynamic range (WDR) neurons in the dorsal horn of the spinal cord. Extracellular activity was recorded from single WDR neurons in the dorsal horn of decerebrate, spinal cord-transected (T-12) cats. Activity was evoked by the presentation of a noxious radiant heat stimulus (51 degrees C) to the cells' receptive fields on the hind paws. Evoked activity was monitored both before and after the spinal administration of either 50 micrograms (n = 6) or 100 micrograms (n = 6) epinephrine. Both doses of epinephrine produced a significant suppression of noxiously evoked activity, which was dose-dependent. In addition, the 100-microgram dose produced a suppression that was of longer duration than that seen following the 50-microgram dose. Recovery from suppression was recorded following both the 50- and 100-microgram dose. These results indicate that spinally administered epinephrine is capable of suppressing noxiously evoked activity of WDR neurons in the dorsal horn of the spinal cord. Since WDR neurons have been identified as cells of origin for the spinothalamic tract, such an action may block the central transmission of afferent pain information. This may be a mechanism by which spinally administered epinephrine enhances the duration or intensity of spinal anesthesia produced by local anesthetics and may also explain spinal analgesia resulting from the spinal administration of adrenergic agonists. Interactions between spinally administered epinephrine and spinally administered opioids also were studied.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of sodium thiopental on the single-unit activity of cells in the nucleus reticularis gigantocellularis (NRGG) were examined in decerebrated cats. Only cells in the NRGC that responded exclusively to electrical stimulation of A-delta fibers (noxious stimulation) in the superficial radial nerve were studied. Sodium thiopental caused a significant, dose-dependent suppression of spontaneous and evoked neuronal activity of cells in the NRGC. Spontaneous activity was suppressed by 66% and 98% after intravenous administration of sodium thiopental, 2.5 mg/kg and 5.0 mg/kg, respectively. Evoked activity was suppressed by 65% and 79%. These findings, when added to previous reports of the suppressive effects of nitrous oxide, morphine sulfate, ketamine hydrochloride, and halothane, suggest the involvement of the NRGC in nociception and provide evidence that sodium thiopental significantly modifies the neuronal message about a noxious stimulus as recorded at the level of the NRGC.

In the operating room or intensive care unit, multiple measurements of circulatory function are almost mandatory in patients with significant cardiovascular disease. Use in these areas requires that the information must be easily organized, rapidly obtained, and inexpensive. A hemodynamic tracking system that meets these criteria is described. This system incorporates a hand-held programmable calculator (cost = $210 to $300) to derive variables computed from standard cardiovascular measurements. The time required to obtain a set of measurements (including thermodilution cardiac output determinations in duplicate), key the numbers into the calculator, and obtain the derived indices is 4 minutes. Two patients, who had acute mitral insufficiency and whose clinical management differed substantially are presented to illustrate the use of data obtained from the hemodynamic tracking system.

Four volunteers judged eight levels of thermal stimuli induced by a Hardy dolorimeter, varying in intensity from extremely painful to a low level seldom even perceived. Half of the 406 stimuli were applied during acupuncture and half either before insertion or after removal of the needles. The experimental design minimized or eliminated factors other than the needles themselves, i.e., no medication was given, the subjects were scientists accustomed to objectivity and, on a preceding day or days, all had become experienced in assigning numbers (individually chosen) to the sensations produced by the different stimuli. Galvanic skin resistance was also tested. The results did not show any influence of acupuncture on perception of pain or on galvanic skin resistance.

The present study was designed to examine the effects of increased magnesium concentration on the nerve block produced by lidocaine, benzocaine, and QX 572 (a quaternary derivative of lidocaine). Desheathed whole sciatic nerves from northern Rana pipiens frogs were placed in a sucrose gap chamber and stimulated at various frequencies at supramaximal intensity for the activation of the compound action potential. After control studies, the nerve was bathed by a calcium-free frog Ringer's solution containing magnesium concentrations of 3.0, 10.0, or 20.0 mM with or without 0.5 mM lidocaine, 0.5 mM benzocaine, or 0.75 mM QX 572. Compound action potentials were measured, and nonfrequency and frequency dependent blocks were compared in each solution. Increased magnesium ion concentration, in the absence of local anesthetics, enhanced the nonfrequency dependent block but did not change the frequency dependent block. All three local anesthetics enhanced both types of block. Increased magnesium concentrations enhanced only the nonfrequency dependent benzocaine block. In contrast, increased magnesium enhanced both types of block produced by QX 572 and lidocaine. These results suggest a potentially important interaction between high magnesium concentrations and local anesthetic nerve blocks.