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Biomedical subjects

J W Grau

Publications and source records attributed to J W Grau.

32 records · Page 2Linked to original sources
PubMed1991

Role of cholinergic systems in pain modulation: I. Impact of scopolamine on environmentally induced hypoalgesia and pain reactivity.

Scopolamine was found to block both brief shock-induced (3 0.75-s, 1.0-mA shocks) and conditioned hypoalgesia on the tail-flick test in rats. The drug also produced a general increase in pain reactivity as measured by both the tail-flick test and shock-induced vocalization. It was shown that this hyperalgesia cannot account for the effect of the drug on brief-shock or conditioned hypoalgesia. Scopolamine did not block the nonopioid analgesia observed after long shock (3 25-s, 1.0-mA shocks). When the effect of the drug on baseline levels of pain reactivity was controlled, it potentiated long shock-induced hypoalgesia. Scopolamine also increased reactivity to tactile stimulation, which suggests the hyperalgesia reflects a general increase in arousal. None of these effects were observed with methylscopolamine, which suggests they are not peripherally mediated.

Animals↗
PubMed1991

Conditioned changes in pain reactivity: II. In search of the elusive phenomenon of conditioned hyperalgesia.

Previous research suggests that a stimulus that has been paired with an aversive event can elicit either an increase (hyperalgesia) or decrease (hypoalgesia) in pain reactivity in rats. Attempts have recently been made to isolate the variables that determine the direction of the conditioned response. Very little evidence has been found for conditioned hyperalgesia when a spinally mediated measure of pain reactivity (the tail-flick test) was used. In the present study, the impact of a conditioned stimulus was assessed using a procedure modeled after one in which conditioned hyperalgesia was obtained with the tail-flick test (Davis & Hendersen, 1985, Experiment 4). With this training paradigm, a discrete conditioned stimulus was found to elicit hypoalgesia but not hyperalgesia.

Acoustic Stimulation↗
PubMed1990

Role of supraspinal systems in environmentally induced antinociception: effect of spinalization and decerebration on brief shock-induced and long shock-induced antinociception.

Prior research suggests that afferent nociceptive information can directly activate the opioid and nonopioid brainstem antinociceptive systems. Grau (1987a) has hypothesized that direct activation occurs when an organism is exposed to severe aversive stimuli and that forebrain systems mediate the activation of the antinociception systems when mild aversive stimuli are used. The present experiments tested this hypothesis by examining the impact of spinalization and decerebration on the antinociception observed after mild (3 0.75-s 1.0-mA shocks) and vs. severe (3 25-s 1.0-mA shocks) tailshocks. It was found that spinal transection eliminated the antinociception observed after both shock schedules, whereas decerebration blocked mild shock-induced, but not severe shock-induced, antinociception. Surprisingly, decerebration potentiated severe shock-induced antinociception. The opioid antagonist naltrexone had no effect on the antinociception observed after severe shock in sham or decerebrate rats.

Afferent Pathways↗
PubMed1990

Associative learning and memory for an antinociceptive response in the spinalized rat.

Prior research suggests that associative and memorial processes can modulate the activation of the endogenous antinociceptive systems. It has been generally assumed that forebrain systems play an essential role in mediating the impact of these processes. The present experiments explored whether the behavioral effects indicative of associative and memorial processes can be obtained in spinalized rats. Experiment 1 demonstrated that a conditioned nonopioid antinociception can be established after rats have experienced a spinal transection at the level of the 2nd thoracic vertebrae. Experiment 2 showed that a postshock distractor can speed the decay of shock-induced antinociception in the spinalized rat. These findings suggest that the circuitry needed to obtain associative and memorylike effects is present within the spinal cord.

Animals↗
PubMed1989

Frontal cortex lesions block the opioid and nonopioid hypoalgesia elicited by brief shocks but not the nonopioid hypoalgesia elicited by long shocks.

Previous research (Grau, 1987a, 1987b) suggests that forebrain systems play an essential role in the hypoalgesia observed after brief shock but not long shock. Additional research has shown that pentobarbital anesthesia and decerebration block the hypoalgesia observed after 3 brief (0.75-s) shocks but not the hypoalgesia observed after 3 long (25-s) shocks. This is a study of whether a specific forebrain lesion, a frontal cortex lesion, would have a similar impact on hypoalgesia induced by brief (0.75 s) and long (25-s) shocks. Frontal cortex lesions, like decerebration and pentobarbital anesthesia, eliminated the hypoalgesia observed after brief but not long shocks. Because other research suggests that the stress of surgery may influence whether the hypoalgesia elicited by shock is opioid or nonopioid, the 2nd experiment was to examine whether the sham operation per se alters the form of the hypoalgesia observed after brief shock. It does not; in the sham-treated subjects, brief shock induced the usual transient nonopioid hypoalgesia followed by prolonged opioid hypoalgesia. These data suggest that frontal cortex lesions block nonopioid and opioid hypoalgesia observed after brief shock.

Animals↗
PubMed1988

The distinction between integral and separable dimensions: evidence for the integrality of pitch and loudness.

Six experiments are reported that investigated the reality and generality of dimensional integrality (Garner, 1974a) by evaluating whether the auditory dimensions of pitch and loudness are psychologically privileged and whether they combine in an integral fashion. In Experiment 1 we psychophysically scaled the dimensions to ensure that, within the stimulus range used, the perceived value on each dimension would remain constant in the face of variation on the other dimension. In Experiments 2 through 4 we assessed performance by using the converging operations by which Garner defined integrality and separability. Experiment 2 showed that in speeded classification, pitch and loudness lead to facilitation with redundant variation and interference with orthogonal variation. Experiment 3 showed that unspeeded classifications are guided predominantly by overall similarity. Experiment 4 established that the better-fitting metric by which multidimensional similarity is appreciated is Euclidean rather than city block. These results suggest that the dimensions of pitch and loudness combine in an integral fashion. In Experiments 5 and 6 we investigated whether the dimensions of pitch and loudness have a privileged status by assessing the impact of rotating the dimensional axes on performance in a speeded sorting task. Experiment 5 looked at six alternative dimensional orientations to pitch and loudness. If anything, rotating the dimensional axes increased the amount of interference in filtering. In Experiment 6 we assessed an alternative dimensional description of the stimuli based on the dimensions of volume and brightness. We found greater interference when the stimuli varied along the dimensions of volume and brightness than when they varied along the dimensions of pitch and loudness. The fact that the least interference is observed when the stimuli vary along the dimensions of pitch and loudness suggests that these dimensions are the more psychologically valid ones. These findings indicate that integrality is not a "myth," that is, merely a case of psychophysical mismatch. Instead, dimensions that are psychologically real are sometimes processed in a unitary fashion.

Acoustic Stimulation↗
PubMed1987

The central representation of an aversive event maintains the opioid and nonopioid forms of analgesia.

Exposure to an aversive event, such as shock, can elicit either an opioid or nonopioid analgesia in rats. We suggest that the central representation of an aversive event in working memory activates both forms of analgesia. We formalize this basic hypothesis by coupling it with a current model of animal learning and memory, SOP (Wagner, 1981). SOP is designed to capture the standard operating procedures that govern memory systems. Our application of SOP suggests that manipulations which disrupt the maintenance of information in working memory should alter the magnitude and time course of analgesia. Three experiments are reported that support our proposal. Experiment 1 showed that analgesia decays more rapidly if the representation of the aversive event is displaced from working memory by presenting a postshock distractor. Experiment 2 demonstrated that the postshock distractor alters the magnitude and time course of both the opioid and nonopioid forms of analgesia. Experiment 3 demonstrated that pharmacologically disrupting working memory, by administering a high dose of pentobarbital, prevents mild shock from inducing a strong change in pain reactivity. Implications of the results are discussed.

Animals↗
PubMed1987

Activation of the opioid and nonopioid analgesic systems: evidence for a memory hypothesis and against the coulometric hypothesis.

It has been suggested that the magnitude and form of hypoalgesia elicited by an aversive event can be predicted from its coulometric product (Intensity X Duration). According to this hypothesis, small products elicit opioid hypoalgesia, and large products elicit nonopioid hypoalgesia. This suggests that increasing the duration of an aversive event should heighten the nonopioid hypoalgesia. Contrary to this prediction, in Experiment 1 I found that increasing the duration of a mild shock attenuated the nonopioid hypoalgesia. In Experiment 2 I tested another implication of the coulometric hypothesis, namely, that mild shocks that have the same coulometric product should elicit equivalent hypoalgesia. The results did not support this prediction. We discuss how these findings are consistent with an alternative theory, the "working memory hypothesis." According to this theory, the representation of an aversive event in working memory elicits hypoalgesia. In Experiment 3 a novel prediction of this theory was tested, namely, that displacing the representation of intense shock from working memory, by following the intense shock with a weak shock "distractor", should attenuate hypoalgesia. The results support this prediction. I conclude by discussing the relation of this work to other findings in the analgesia literature.

Animals↗
PubMed1985

Analysis of the unique cue in configural discriminations.

Four experiments used an autoshaping procedure with pigeons to investigate the basis of configural discriminations. The elements of both a negative patterning (A+, B+, AB-) and a conditional discrimination (AC+, BD+, AD-, BC-) were paired, in a second-order procedure with two new key lights, X and Y. Responding was then tested to X and Y presented in compound with each other and with A and B. The pattern of responding to compounds containing X and Y was like the pattern of responding to compounds containing their associates, A and B. This suggests that A and B can be replaced by their associates without disrupting responding to their compounds. Because X and Y are physically different from A and B, this in turn suggests that any unique cue controlling responding to their compounds does not depend on the physical presence of the component stimuli. Instead the unique stimulus appears to arise from the joint activation of memory representations.

Animals↗
PubMed1984

Influence of naloxone on shock-induced freezing and analgesia.

Six experiments were designed to examine whether mild shock activates an opiate analgesia in rats. The first three experiments explored whether naloxone potentiates shock-induced freezing by blocking an opiate analgesia. In Experiment 1, subjects treated with either a low or a high dose of naloxone froze more following mild shock. Experiment 2 revealed that both dose levels of the drug increase pain reactivity. The results of Experiment 3 suggested that a naloxone-induced increase in pain reactivity accounts for the drug's effect on freezing. The last three experiments investigated the nature of the analgesia induced by mild shock. In Experiment 4, mild shock induced a profound analgesia as measured by the tail-flick test. Experiment 5 demonstrated that mild shock elicits a transient naloxone-insensitive analgesia which rapidly dissipates to reveal an analgesia that is reversed by a high dose of naloxone. This suggests that mild shock activates both the nonopiate and the opiate form of analgesia. Experiment 5 also showed that a low dose of naloxone potentiates shock-induced analgesia. Experiment 6 revealed that this potentiated analgesia is attenuated by a high dose of naloxone. Implications of the results are discussed.

Animals↗
PubMed1982

Extent and control of shock affects naltrexone sensitivity of stress-induced analgesia and reactivity to morphine.

Opioid and nonopioid mediated changes in pain sensitivity have been observed after exposure to various stressful conditions. A series of inescapable shocks sequentially produces an early form of analgesia which is not affected by the opiate antagonist, naltrexone, and a late antinociceptive response which is sensitive to reversal by naltrexone. Here, this is shown to be true over a wide range of doses. In a further experiment subjects given either escapable or inescapable shock were analgesic immediately after the stress session. However, the analgesia of inescapably shocked subjects was more sensitive to reversal by naltrexone. A final experiment revealed that inescapably shocked subjects, but not escapably shocked subjects, were hyperreactive to the analgesic effects of morphine 24 hr after shock. These results suggest that activation of an opiate system occurs only after extended exposure to stress and that this activation is greater when the stress is inescapable. Implications for opioid versus nonopioid mechanisms of stress-induced analgesia are discussed.

Animals↗
PubMed1981

Cross tolerance between morphine and the long-term analgesic reaction to inescapable shock.

Animals exposed to a variety of stressors display a temporary analgesic reaction. This short-term analgesia has been shown to be reversible by opiate antagonists and cross-tolerant with morphine following some stress conditions, but not following others. It has recently been shown that inescapable shock parameters which produce behavioral '"learned helplessness" effects also produce a short-term analgesic reaction, and that this reaction can be re-aroused by a brief exposure to shock 24 hours later. Further, both the immediate and long-term antinociceptive reaction which follow shocks of this type have been shown to be reversible by opiate antagonists. Here it is shown that the long-term analgesic reaction is completely cross tolerant with morphine. Implications of these results for opioid mediation of learned helplessness and opioid versus nonopioid mediation of stress-induced analgesia are discussed.

Animals↗
PubMed1980

Opiate antagonists and long-term analgesic reaction induced by inescapable shock in rats.

Five experiments examined the influence of opiate antagonists on both the short-term analgesic reaction resulting 30 min after exposure to inescapable shock and the long-term analgesic reaction resulting after reexposure to shock 24 hr after inescapable shock exposure. Experiment 1 showed that the long-term analgesic reaction could be reduced by administration of naltrexone prior to exposure to inescapable tail shock. Experiment 2 showed that the reduction in the long-term analgesic reaction produced by naltrexone was dose-dependent. Experiment 3 showed that the long-term analgesic reaction could also be reduced by administration of naltrexone prior to reexposure to shock. Experiment 4 showed that the long-term analgesic reaction could be reduced by administration of large dose of naloxone prior to reexposure to shock. Experiment 5 showed that the short-term analgesic reaction was reduced by naltrexone administered prior to inescapable shock. Some implications of these results for the biochemical substrates of both learned helplessness and stress-induced analgesia are discussed.

Animals↗