Izabella Panocka

Inheritance of stress-induced analgesia in mice. Selective breeding study

Random mated Swiss mice swam for 3 min at 20 degrees C. The animals with less than or equal to 10 s and greater than or equal to 50 s postswim latencies on the hot plate (56 degrees C) were selected as progenitors of low (LA) and high (HA) analgesia lines, respectively. Gradual divergence of latency distributions and postswim hind paw flick latencies between the two lines was observed in successive generations. As shown by the tail flick test applied to the sixth offspring generation, postswim analgesia in the HA line was not only more pronounced but also lasted longer compared to the LA line and the unselected controls. Possible differentiation of the endorphin system activity in the course of selection is discussed.

Differentiation of neurochemical basis of stress-induced analgesia in mice by selective breeding

Two selectively bred lines of mice, one responding with high (HA) and the other with low analgesia (LA) to 3 min swims at 20 degrees C were compared with respect to naloxone ability to reverse such swim induced pain threshold elevation. Also, the analgesic effect of morphine was tested in both lines of mice. Naloxone at a dose of 1 mg/kg significantly reduced postswim analgesia determined with hot plate and tail flick tests in HA mice, but was not effective in LA mice. HA mice responded with significant elevation of hot plate threshold to 0.1 mg/kg of morphine hydrochloride, whereas in LA mice comparable level of analgesia developed after 12.8 mg/kg. The data argue for greater involvement of opioid mechanisms in producing analgesia in HA mice than in LA mice, and so for inheritance of endorphin system(s) activity.

Selective breeding of mice for high and low swim analgesia: differential effect on discrete forms of footshock analgesia

&NA; Selective breeding of mice displaying high and low swim‐induced analgesia led to the development of two animal lines divergent in the magnitude of analgesic response to swimming. In this study, animals belonging to the seventh generation of both lines were exposed to two temporally different forms of footshock, one of which produced opioid and the other non‐opioid analgesia. We found that selective breeding for high and low swim‐induced analgesia exerted a striking influence on the magnitude of the opioid‐mediated type of footshock analgesia, but was ineffective on that of the non‐opioid type.

Enhancement of stress-induced analgesia in adrenalectomized mice: its reversal by dexamethasone.

Abstract Adrenalectomy significantly increased the level of analgesia induced by room temperature swimming in mice, as revealed by a hot-plate test. This augmentation of antinociceptive action of stress was abolished by dexamethasone pretreatment. Involvement of pituitary opioids in modulating post-stress pain sensitivity in mice is suggested.

Cross-tolerance between morphine and swim analgesia in mice selectivity bred for high and low stress-induced analgesia

Mice selectively bred for high (HA) and for low analgesia (LA) induced by 3-min swimming at 20 degrees C and unselected controls (C) were injected three times daily for 3 days with 20 mg/kg morphine HCl. The analgesic effect of 10 mg/kg morphine in nontolerant mice differed between the lines in the rank order of HA > C > LA and significantly decreased after repeated treatment with morphine, as revealed by the hotplate test (56 degrees C). The tolerance to morphine analgesia was more pronounced in HA than in C mice but did not develop at all in LA mice. Similarly, the magnitude of swim-induced analgesia in morphine tolerant mice decreased to a greater degree in the HA than the C line but did not change in LA mice. Naloxone HCl (1 and 10 mg/kg) attenuated swim analgesia more in nontolerant HA than C mice but had no effect in morphine-tolerant HA and C and in all LA mice. The differential degree of morphine tolerance and cross-tolerance with swim analgesia suggests that the strategy of selective breeding toward divergent magnitudes of stress-induced analgesia has differentiated opioid involvement in endogenous pain inhibition in the selected lines.

Tolerance and cross-tolerance with morphine in mice selectively bred for high and low stress-induced analgesia

Mice selectively bred for high (HA) and low (LA) swim-induced analgesia were exposed to two different stress paradigms; one consisting of a 3-min swim at 20 degrees C daily for 14 days, and the other consisting of 3-min swims repeated at 2-h intervals for 48 h. Both forms of chronic stress resulted in the development of tolerance to swim-induced antinociception to a greater degree in the HA mice than in control (C) mice, but were both ineffective at inducing tolerance in LA mice. Swimming repeated at 2-h intervals for 48 h resulted in cross-tolerance with morphine in HA and C mice. Naloxone (1 and 10 mg/kg, IP) failed to antagonize swim-induced analgesia in mice that had experienced chronic swimming in the 2-h/48-h paradigm. The daily swimming paradigm failed to produce cross-tolerance with morphine analgesia in any line. Differential degree of tolerance in three lines supports a hypothesis that selective breeding for high and low stress-induced analgesia has modified the degree of opioid involvement in the endogenous analgesia mechanisms.

Potentiation of swim analgesia by D-amino acids in mice is genotype dependent.

The effect of combined treatment with 125 mg/kg of D-phenylalanine plus 125 mg/kg of D-leucine (IP) on magnitude and duration of analgesia caused by 3 min swim at 20 degrees C was studied in mouse lines selectively bred for 20 generations toward high and low level of stress-induced analgesia. The D-amino acids administered 30 min prior to swimming increased postswim tail-flick latencies and prolonged antinociception more in the high analgesia line (HA) than in concomitantly bred unselected controls, but were not effective in the low analgesia line (LA). The potentiation of swim analgesia by D-amino acids was prevented by simultaneous administration of 1 mg/kg of naloxone hydrochloride which, given alone, antagonized the analgesia more in the HA line than in controls, but not in the LA line. The results are interpreted in terms of genetic differentiation of opioidergic transmission in the selectively bred mouse lines.

Adrenalectomy and dexamethasone differentially affect postswim antinociception in mice selectively bred for high and low stress-induced analgesia

The effects of dexamethasone and naloxone on analgesia induced by swimming (3 min, 20 degrees C) were studied in the 6th and 7th generations of adrenalectomized and intact mice selectively bred for high (HA) and low (LA) postswim analgesia. Swim-induced analgesia in intact HA animals was significantly reduced by naloxone and dexamethasone while in LA mice these two compounds were ineffective. Naloxone ability to reverse adrenalectomy-caused swim analgesia increase was much greater in HA than in LA mice. In both intact and adrenalectomized HA animals dexamethasone and naloxone decreased postswim analgesia to the level observed in LA mice. It is suggested that selective breeding for high and low swim analgesia modified the extent of pituitary-adrenal axis involvement in the generation of stress-induced analgesia.

Dexamethasone reverses adrenalectomy enhancement of footshock induced analgesia in mice

Abstract Footshock induced analgesia in mice was significantly enhanced by adrenalectomy. This effect of pituitary-adrenal axis disruption was reversed by dexamethasone. Involvement of pituitary factor(s) in producing this form of stress induced analgesia in mice is suggested.

Activation of anti- and pro-nociceptive mechanisms by front paw shock in spinal mice: Involvement of humoral factors

The effect of prolonged, intermittent front paw shock on nociception was studied in two groups of differently spinalized mice. The animals, spinalized so that the dura was left intact to allow free cerebrospinal fluid (CSF) passage, exhibited post-foot shock increase in latencies of spinally-mediated nociceptive reflexes. This anti-nociception was completely blocked by naloxone. A facilitation of nociceptive reflexes was observed in animals in which the spinal cord was ligated together with the dura. The results indicate that: front paw shock in mice leads to activation of supraspinal sites which mediate anti-nociception by releasing substance(s) reaching the spinal cord via the CSF route; single stressors may simultaneously activate both anti- and pro-nociceptive mechanisms.