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John C Liebeskind

Publications and source records attributed to John C Liebeskind.

10 recordsLinked to original sources
PubMed1995

One or two genetic loci mediate high opiate analgesia in selectively bred mice.

The analgesic responses of humans and laboratory animals are characterized by substantial individual differences. The genetic basis of this variability can be studied experimentally in rodents using a program of selective breeding. One such program selected for high (HA) and low (LA) swim stress-induced analgesia (SSIA) on the hot-plate (56 degrees C) test in Swiss-Webster mice. These lines, which have been selectively bred for more than 25 generations, display markedly divergent opioid-mediated SSIA (3-min swims in 38 degrees C water), morphine analgesia (10 mg/kg, i.p.), and analgesia to the kappa-receptor agonist, U-50,488H (30 mg/kg, i.p.). The present study investigated the mode of inheritance of these opioid analgesias in HA and LA mice, using Mendelian genetic analyses. We report that the differential sensitivity of HA and LA mice to each of these analgesic manipulations appears to be determined oligogenically, by one or at the most two major genetic loci. The loci associated with each type of analgesia do not co-segregate, however, indicating that three distinct oligogenic effects have been identified. These findings suggest that the genetic determination of analgesic mechanisms may have simple components and as such may be amenable to further analysis using molecular genetic techniques.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1995

Neonatal testosterone exposure influences neurochemistry of non-opioid swim stress-induced analgesia in adult mice.

The effects of neonatal hormone manipulations on swim stress-induced analgesia (SSIA) magnitude and neurochemical quality were examined in Swiss-Webster mice of both sexes. Previous research has indicated that non-opioid SSIA mechanisms in adult Swiss-Webster mice are sexually dimorphic. Male mice exhibit non-opioid SSIA following a 3-min swim in cold (15 degrees C) water that is antagonized by the non-competitive NMDA antagonist MK-801 (dizocilpine; 0.075 mg/kg), whereas female mice do not display NMDA-mediated analgesia in the presence of estrogen. Since male and female mice show equipotent magnitudes of SSIA, it was concluded that female mice display a neurochemically distinct, estrogen-dependent SSIA mechanism specific to their gender. In the present study, female mice exposed to testosterone during the neonatal period display NMDA-mediated analgesia even in the presence of estrogen in adulthood. Thus, expression of the female-specific, estrogen-dependent SSIA mechanism previously described may be dependent on the absence of testosterone during early ontogeny.

Analgesia↗
PubMed1993

Sex differences in the antagonism of swim stress-induced analgesia: effects of gonadectomy and estrogen replacement.

Sex differences in the neurochemical mediation of swim stress-induced analgesia (SSIA) were examined in Swiss-Webster mice. Intact and gonadectomized adult mice of both sexes were tested for their analgesic response (hot-plate test) to 3 min of forced swimming in 15 degrees C and 20 degrees C water. SSIA resulting from 15 degrees C swim was previously shown to be naloxone-insensitive (i.e., non-opioid) whereas SSIA resulting from 20 degrees C swim produced an analgesia that was partially reversible by naloxone (i.e., mixed opioid/non-opioid). The non-opioid components of these SSIA paradigms were attenuated by the N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK-801). We now report that in males, but not females, dizocilpine (0.075 mg/kg, i.p.) and naloxone (10 mg/kg, i.p.) antagonized the non-opioid and opioid components of SSIA, respectively. After ovariectomy, females displayed a pattern of antagonism similar to males such that dizocilpine attenuated non-opioid SSIA, although naloxone remained ineffective in antagonizing 20 degrees C SSIA. Thus, SSIA in intact females was neither opioid- nor NMDA-mediated, yet it was of similar magnitude to the SSIA displayed by intact males. In separate experiments, estrogen replacement (estrogen benzoate; 5.0 micrograms/day, i.p.) administered to ovariectomized mice over a 6-8 day period reinstated the dizocilpine-insensitivity of 15 degrees C SSIA characteristic of intact females. However, a similar estrogen regimen administered to both intact and castrated males did not compromise the sensitivity to dizocilpine previously noted in male mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1993

Morphine attenuates surgery-induced enhancement of metastatic colonization in rats.

Painful stressors such as surgery have been shown both to suppress immune function and to enhance tumor development. Whether the immune system mediates the tumor-enhancing effects of surgery remains unclear. Moreover, the role of postoperative pain has been largely ignored in such studies. To explore these issues, we used the MADB106 tumor, a mammary adenocarcinoma syngeneic to the subjects of this study (Fischer 344 rats) and known to be sensitive to natural killer (NK) cell activity. We found that surgery enhanced metastatic colonization and that this tumor-enhancing effect occurred only during the time in which the MADB106 tumor is sensitive to NK control. These results support the hypothesis that suppression of NK cell activity mediates the surgery-induced enhancement of metastatic colonization. Further, we found that an analgesic dose of morphine blocked the surgery-induced increase in metastasis without affecting metastasis in unoperated animals. These findings suggest that postoperative pain is a critical factor in promoting metastatic spread. If a similar relationship between pain and metastasis occurs in humans, then pain control must be considered a vital component of postoperative care.

Adenocarcinoma↗
PubMed1992

NMDA receptor antagonist MK-801 blocks non-opioid stress-induced analgesia in the formalin test.

The analgesic effect of a 3-min swim stress was assessed using the formalin test. Male Swiss mice were injected i.p. with naloxone (0.1 or 1.0 mg/kg), MK-801 (0.075 mg/kg) or saline 15 min prior to swimming in water maintained at 20 degrees C or 32 degrees C. The mice were then injected with 20 microliters of 5% formalin into the plantar surface of 1 hind paw and pain behaviour (time spent licking the injected paw) was continuously monitored during the subsequent 10 min. Swim stress produced a significant reduction in pain behaviour at both 20 degrees C and 32 degrees C. MK-801 completely blocked the analgesia produced by both the 20 degrees C and 32 degrees C swim. At a dose of 0.1 mg/kg, naloxone partially antagonized the analgesia produced by the 32 degrees C swim but did not affect the analgesia produced by the 20 degrees C swim. Naloxone at a dose of 1.0 mg/kg had no effect on swim stress-induced analgesia. Neither MK-801 nor 0.1 mg/kg naloxone altered baseline pain behaviour, although 1.0 mg/kg naloxone did significantly reduce it. It is unlikely that the effect of MK-801 on swim stress-induced analgesia is due to an interaction with an opioid mechanism, as MK-801 had no effect on morphine analgesia. These results suggest that the analgesia produced by the 20 degrees C swim stress in the formalin test is non-opioid in nature and mediated via the NMDA receptor, whereas the 32 degrees C swim stress-induced analgesia has both an opioid and non-opioid component.

Analgesia↗
PubMed1991

Pain can kill.

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Humans↗
PubMed1985

Stress-induced analgesia in the mouse: strain comparisons.

Inescapable footshock is capable of differentially activating opioid- and non-opioid-mediated mechanisms of stress-induced analgesia in the rat, depending on the temporal and intensive parameters of its administration. In this study we compared the effects of opioid and non-opioid stress analgesia in two strains of mice, one known to be deficient in central opioid binding sites (CXBK) and one normal in this regard (C57BL/6BY). We found that although the C57 strain showed robust opioid and non-opioid stress analgesia, the CXBK strain only showed stress analgesia of the non-opioid type.

Analgesia↗
PubMed1978

Effects of pain-attenuating brain stimulation and morphine on electrical activity in the raphe nuclei of the awake rat.

Evoked potential and multiple unit responses to noxious shock and pinch as well as to innocuous air puffs were recorded in the dorsal raphe, median raphe and raphe magnus nuclei of awake rats. Concurrent measurements of various behavioral responses to noxious stimuli were also made. Electrical stimulation of midbrain central gray and of medial thalamus, as well as systemic administration of morphine, greatly diminished all behavioral and electrophysiological responses to noxious stimuli without reliably affecting responses to air puffs. At the same time that brain stimulation and morphine attenuated nociceptive responses, a significant elevation was seen in the spontaneous multiple unit activity of these brain areas, particularly nucleus raphe magnus. In another group of animals, a comparison was made of the analgesic effectiveness of stimulation sites in the bulbar raphe (including raphe magnus) and sites dorsal or lateral to this region. More consistently potent effects were obtained from the raphe placements. These findings point to the importance of the bulbar raphe in mechanisms of analgesia. It is suggested that brain stem stimulation and morphine administration activate descending controls of raphe origin which selectively inhibit nociceptive elements in the spinal cord.

Animals↗
PubMed1976

Inhibition of visceral pain by electrical stimulation of the periaqueductal gray matter.

Numerous recent studies demonstrated that electrical stimulation of the periaqueductal gray matter (PGM) can result in powerful analgesia to pain of somatic origin. In the present study, we have developed a visceral pain test employing intraperitoneal injection of hypertonic saline which yields a writhing response in the adult rat more reliably than other pain-producing substances. With this test we show that writhing as well as the response to radiant heat (tail flick test) are completely inhibited in all animals with PGM electrode placements.

Analgesia↗