On the absence of correlation between responses to noxious heat, cold, electrical and ischemic stimulation.

Is a person's response to one noxious stimulus similar to his/her responses to other noxious stimuli? This long-investigated topic in pain research has provided inconclusive results. In the present study, 2 samples were studied: one using 60 healthy volunteers and the other using 29 patients with coronary artery disease. Results showed near-zero correlations between measures of heat, cold, ischemic, and electrical laboratory pains, as well as between these laboratory pains and an idiopathic pain, the latency to exercise-induced angina in the patients. Power analyses showed that the sample sizes were sufficient to detect a correlation of 0.50 or greater at the 0.05 level 99% of the time in the healthy volunteers, and between 80 and 85% of the time in the patients. Reliability analyses indicated retest correlations on the order of 0.60 for these measures, indicating that the lack of correlation between modalities was not due to unreliability within a measure. These studies fail to demonstrate alternate-forms reliability among these tests, and also fail to support the notion that a person can be characterized as generally stoical or generally complaining to any painful stimulus. In practice, this implies that a battery of tests should generally be used to assess pain sensitivity and also that assessments of one pain modality are not generally useful for making inferences about another.

Characterization of pituitary mediation of stress-induced antinociception in rats.

Antinociception, induced by continuous cold-water swims (CCWS) and certain parameters of inescapable foot shock, is reduced in hypophysectomized rats receiving supplements of corticosterone and l-thyroxine. To assess which lobe of the pituitary gland is involved in this effect, the first experiment compared the effects of total hypophysectomy and posterior lobectomy in supplemented rats upon CCWS antinociception on the tail-flick and jump tests and upon continuous inescapable foot shock antinociception on the tail-flick test. Total hypophysectomy, but not posterior lobectomy, significantly reduced CCWS antinociception on both tests in supplemented rats relative to sham surgery. Both total and posterior hypophysectomy either reduced or potentiated foot shock antinociception as functions of shock intensity or duration of exposure in supplemented rats. To assess whether hormonal supplementation is necessary for the observed effects, the second experiment examined CCWS antinociception in sham-operated and hypophysectomized rats that received either no hormonal supplements or corticosterone and/or l-thyroxine. These regimens failed to alter CCWS antinociception in sham-operated rats. Treatment of hypophysectomized rats with corticosterone and l-thyroxine either separately or together significantly reduced CCWS antinociception. In contrast, if hypophysectomized rats did not receive supplements, CCWS antinociception was significantly potentiated relative to sham-operated controls. These effects could not be attributed to treatment-induced changes in either body weight or CCWS hypothermia. These data suggest that the anterior lobe of the pituitary gland and adrenal cortex are involved in the mediation and/or maintenance of CCWS antinociception.

Tangent Streak RGP bifocal contact lenses in the treatment of accommodative esotropia with high AC/A ratio.

Patients with the diagnosis of high accommodative convergence/accommodation (AC/A) ratio, accommodative esotropia traditionally have been fit with bifocal spectacles. For cosmetic reasons, however, many patients prefer non-spectacle correction. Orthoptics, miotics, contact lenses, and surgery have been used as alternatives. We describe the treatment of three patients with the Tangent Streak bifocal rigid gas permeable (RGP) contact lens in which functional control of the patient's deviation was attained. Tangent Streak RGP bifocal contact lenses offer an acceptable alternative to bifocal spectacles, surgery, miotics, or orthoptics in the treatment of accommodative esotropia with high AC/A ratio.

The principle of mutual exclusivity in word learning: to honor or not to honor?

According to Markman and Wachtel, children assume that nouns pick out mutually exclusive object categories, and so each object should have only one category label. While this assumption can be useful in word learning, it is not entirely reliable. Therefore, children need to learn when to and when not to make this assumption. 6 studies examined whether knowledge about hierarchical organization of categories and about cross-language equivalents for object labels can help children limit their use of this assumption appropriately. These studies revealed that adults as well as children resisted assigning 2 novel names to the same object in some situations. By age 4, children also seemed to know enough about categorization to accept 2 names for an object if the names picked out categories from different levels of a hierarchy (e.g., animal and lemur) but not if they picked out categories from the same level (e.g., lemur and seal). Moreover, monolingual as well as bilingual children seemed to know enough about languages to accept 2 names for the same object if the names clearly came from different languages. Together, these findings suggest that even preschool children can make use of knowledge about language and categorization to fine tune the mutual exclusivity assumption in order to use it effectively in word learning.

The effects of intrahypothalamic hemicholinium-3 on muricide, irritability and feeding.

Male Long-Evans rats that consistently killed mice when food deprived were injected unilaterally in the lateral hypothalamus with 20 micrograms and 30 micrograms of the acetylcholine synthesis inhibitor hemicholinium-3 (HC-3) and saline in a counterbalanced order. Rats were evaluated 1, 2, 3, 24, 48 and 72 hours post-injection for effects on muricide, irritability and feeding. HC-3 suppressed muricide and feeding and produced a trend toward reduced irritability during the first three hours post-injection. These data indicate that modulation of cholinergic systems in the lateral hypothalamus influences several behaviors and not any one behavior specifically.

Disinhibition of muricide and irritability by intraseptal muscimol.

In two experiments we have found and replicated the observation that intraseptal muscimol profoundly facilitates muricide. It also increases irritability (response to handling). These effects are specific to aggressive behaviors in that the drug affects neither activity nor chocolate chip acceptance. The effects of the GABA synthesis inhibitor thiosemicarbazide depend upon the site of injection within the septum; in more anterior loci the drug produces the expected increase in muricide latency; in more posterior sites it produces an anomalous facilitation of muricide. The serotonergic agents quipazine and metergoline have no significant effect when injected into any of these sites. These results suggest that the septal neurons mediating the muricide-inhibitory effect of electrical stimulation [29] are subject to local, GABAergic, control. Inhibition of these neurons by muscimol produces a net disinhibition of muricide.

Effects of chronic d-amphetamine on the maintenance and acquisition of schedule-induced polydipsia in rats.

The effects of chronic d-amphetamine on the acquisition of schedule-induced polydipsia and its maintenance by stimuli paired with food were evaluated in three interlocking experiments. In Experiment 1, polydipsia was induced in rats exposed to a response-independent fixed-time schedule in which a food pellet (US) was paired with a stimulus complex of lights and tone (CS) every 45 sec. When food was omitted and only the CS was presented rats drank very little water. Rats were then pretreated with 1 mg/kg d-amphetamine for 15 CS-US sessions and two or three subsequent CS-alone sessions. Animals remained polydipsic during CS-US sessions and drank little water during CS-alone sessions. However, d-amphetamine improved control exerted by the CS over drinking relative to no-drug sessions. In Experiment 2, acquisition of schedule-induced polydipsia during 10 sessions exposure to the periodic CS-US schedule was blocked in rats pretreated with 1 mg/kg d-amphetamine, compared with rats pretreated with buffer. During subsequent CS-alone sessions the temporal control of drinking by the CS was greater in the rats exposed to amphetamine. In Experiment 3, the rats that had not acquired polydipsia while under d-amphetamine in the previous experiment, all became polydipsic when pretreated with buffer. All rats remained polydipsic when re-exposed to amphetamine pretreatment. These results indicate that chronic d-amphetamine administration can facilitate control of licking and drinking by nonfood stimuli paired with food, and can block acquisition of schedule-induced polydipsia.

Facilitation of muricide in rats by cholinergic stimulation of the lateral hypothalamus.

The effect of cholinergic stimulation of the lateral hypothalamus on muricide in rats was evaluated in two experiments. In Experiment 1, injections of the cholinergic agonist carbachol (5.0-20.0 micrograms) were found to facilitate muricide in rats that spontaneously killed mice. In Experiment 2, rats were induced to kill mice by food deprivation and then stimulated with carbachol (2.5-5.0 micrograms). Facilitation of muricide was found to be coincident with increased scores on a handling difficulty (irritability) scale for the majority of rats. These results suggest that facilitation of muricide by cholinergic stimulation of lateral hypothalamic areas may be related to increases in irritable aggression.

Reversal of stress-induced analgesia by apomorphine, but not by amphetamine.

Acute exposure to severe stressors induce profound analgesia as well as depleting catecholamine levels. The present study examined whether d-amphetamine and apomorphine, agents which increase catecholamine availability, would alter the analgesic effectiveness of cold-water swims (CWS) and 2-deoxy-D-glucose (2-DG) as measured by an operant liminal escape procedure. Two groups of 10 rats each were tested to determine alterations in liminal escape threshold functions following amphetamine at doses of 0.25, 0.5, 1, 2 mg/kg and following apomorphine at doses of 0.025, 0.05, 0.1, 0.2 mg/kg. Half of the amphetamine and half of the apomorphine groups were tested across their respective dose ranges for the drug effects upon CWS analgesia. The remaining animals in each group received 2-DG (600 mg/kg IP) alone followed by 2-DG paired with each stimulant dose. No dose of amphetamine or apomorphine alone altered escape thresholds. While amphetamine produced slight potentiations of 2-DG analgesia at the two low doses, apomorphine at the 0.05 and 0.1 mg/kg doses returned CWS and 2-DG analgesia to within normal placebo values. These results provide indirect evidence for a role for brain norepinephrine and dopamine in stress-induced analgesia, and these data are discussed with respect to catecholamine involvement in pain-inhibitory processes.

Stress-induced analgesia: neural and hormonal determinants.

Extensive evidence has indicated that distinct neural systems specifically designed to inhibit sensitivity to painful stimuli exist. Recent advances suggest that the endorphins, enkephalins and the opiate receptor interact with a descending serotonergic bulbospinal system to mediate the analgesic responses to opiates and electrical stimulation. In assessing the evolutionary and behavioral significance of this pain-inhibitory system, several laboratories discovered that acute exposure to a wide variety of stressful events results in a transient analgesia. Chronic exposure to a number of these stressors results in adaptation of the analgesic response. The purpose of this review is to identify and characterize the mechanisms by which these stressors activate pain-inhibition. The relationship of stress-induced analgesia to each of the following is reviewed: (a) the role of endorphins, enkephalins and the opiate receptor; (b) the role of the descending serotonergic bulbospinal system; (c) the role of the pituitary gland; and (d) the role of hypothalamic mechanisms. Data will be discussed in terms of "opiate" and "non-opiate" pain-inhibitory mechanisms, in which some stressors act through the former and other stressors act through the latter.

Chlordiazepoxide antinociception: cross-tolerance with opiates and with stress.

Chlordiazepoxide (CDP) has been previously shown to possess antinociceptive properties that are resistant, except at high doses, to the opiate antagonist naloxone. The present study evaluated whether CDP's antinociceptive effects were subject to tolerance following repeated injections and whether cross-tolerance might develop between the antinociceptive action of CDP and that of either morphine or cold water swins. CDP increased flinch-jump thresholds following acute administration and exhibited tolerance following repeated injections. Neither morphine-tolerant nor cold water swim-adapted rats displayed an antinociceptive effect when tested with CDP. On the other hand, chronic pretreatment with CDP attenuated the antinociceptive effects of cold water swims, but did not produce any clear effect upon morphine analgesia.

2-Deoxy-D-glucose analgesia: influences of opiate and non-opiate factors.

Acute administration of 2-deoxy-D-glucose (2-DG), an antimetabolic glucose analogue induces a powerful analgesia which adapts following repeated administration. 2-DG analgesia displays significant cross-tolerance with morphine, and like morphine analgesia, is potentiated in hypophysectomized rats. The present study examined further the role of opiates in 2-DG analgesia by examining whether the opiate antagonist, naloxone, would affect 2-DG analgesia, and whether ineffective doses of 2-DG and morphine would interact in a synergistic fashion to induce analgesia. Nociceptive thresholds were measured by the flinch-jump test. Naloxone doses of 1, 5, 10 and 20 mg/kg were all ineffective in reducing significantly 2-DG (600 mg/kg) induced pain threshold elevations. Naloxone failed to attenuate 2-DG (350 mg/kg) analgesia whether administered before or after the 2-DG injection. On the other hand, simultaneous administration of sub-analgesic doses of 2-DG (200 mg/kg) and morphine (2.5 mg/kg) summated to produce significant analgesia. This, 2-DG analgesia is similar to opiates in its tolerant and summative actions, yet dissimilar in that naloxone is ineffective in reversing its effects.

Differential effects of hypophysectomy upon analgesia induced by two glucoprivic stressors and morphine.

Pain threshold elevations induced in rats following acute exposure to stressful cold-water swims and to inescapable foot shocks are significantly attenuated by hypophysectomy. The present study investigated the effects of hypophysectomy upon the dose-dependent and time-dependent analgesia induced by morphine and by the glucoprivic agents, 2-deoxy-D-glucose (2-DG) and insulin. Two reflex pain tests, the tail-pinch and the flinch-jump were employed. In normal rats, insulin induced prolonged (180 min) analgesia at doses of 16 U/kg on the tail-pinch test and 256 U/kg on the flinch-jump test. However, the same agents induced small and brief pain threshold elevations in hypophysectomized animals. By contrast, though 2-DG increased both measures in both groups, its effects were more marked in hypophysectomized rats. Hypophysectomized rats also exhibited a potentiated analgesic effect on both tests following high doses of morphine. On the other hand, low doses of morphine transiently increased tail-pinch thresholds in normal, but not hypophysectomized subjects. These data provide further evidence of multiple pain-inhibitory mechanisms in which the pituitary plays a complex, but integral part.

Analgesia induced by cold-water stress: attenuation following hypophysectomy.

In addition to the well-known activation of the pituitary-adrenal axis, acute exposure to severe stressors includes a temporary analgesia in rats. Thus, the present study investigates whether the pituitary was involved in the mediation of analgesia induced by severe cold-water swim (CWS) stress. Flinch-jump thresholds were measured 30 min following 3.5-min swims in water temperatures ranging from 2-35 degrees C. Compared with untreated normal rats, hypophysectomized rats, receiving corticosterone and thyroxin, displayed significantly less CWS-induced analgesia, while similarly-supplemented normal rats exhibited significantly more CWS-induced analgesia. In a second experiment, operant liminal escape pain thresholds were determined following acute and chronic CWS. Whereas normal rats exhibited profound analgesia following the initial swims, the hypophysectomized rats never displayed any CWS-induced operant escape shifts. Stress-induced alterations in general activity levels and/or thermoregulation were shown to be unrelated to the diminished effectiveness of CNS to produce analgesia in hypophysectomized rats. These data imply that the pituitary is involved in the mediation of CWS-induced analgesia.