Kenneth Gross

Studies on the intrathecal effect of β-endorphin in primate

The intrathecal administration of beta-endorphin in the primate through an indwelling spinal catheter, produced a significant elevation in the nociceptive threshold as measured by the discrete trial shock titration task. The time of onset, duration of effect and magnitude of effect were all dose-dependent over a range of 150-750 micrograms. The effects were antagonized in a dose-dependent fashion by the systemic administration of naloxone. Aside from the elevations in the shock titration threshold produced by intrathecal beta-endorphin, no untoward effects on the animals motor function or behavioral reactivity was noted. Significantly, unlike morphine, intrathecal beta-endorphin failed to produce any signs of scratching behavior at the doses used in these experiments. Once daily administration of intrathecal beta-endorphin (500 micrograms) showed a significant progressive decline in the antinociceptive effect over an 8-day period. Animals made tolerant to beta-endorphin in this fashion showed a significantly reduced response to an otherwise active dose of intrathecal morphine, indicating evidence for cross tolerance.

John Donne’s Lyric Skepticism: In Strange Way

ç 2004 by The University of Chicago. All rights reserved. 0026-8232/2004/10103-0002

Pharmacology Studies on the intrathecal effect of endorphin in primate: Brain Res., 241 (1982) 261–269

10.00 In 1601, John Donne composed a satirical allegory titled The Progresse of the Soule, or Metempsychosis. Written in stanzas pointedly mirroring those of Spenser’s Faerie Queene—nine pentameter lines and final hexameter, with a less interwoven, more abrupt rhyme-scheme than Spenser’s, aabccbbddd—this dense, apparently unfinished text of 520 lines recounts the successive transmigrations of a nameless but deathless soul through a variety of human and animal forms. The soul in Metempsychosis is a peculiar entity, a spirit of innovation, heresy, usurpation, and perverse appetite; it has a life at once human and inhuman, natural and historical. Abject, repugnant, inchoate, isolated, the soul holds a hard sort of charm. And its homes are myriad. They include, by turns, the tree of knowledge in the Garden of Eden (which later, Donne adds in line with medieval legend, provided the wood for the Cross); an anthropomorphic mandrake root, whose extract can serve as both a poison and an aphrodisiac, and also as something to induce abortions; a lustful, self-wasting sparrow; several hapless fishes; a ponderous and tyrannical whale, himself slain by a conspiracy of two other fish; a Machiavellian mouse, who crawls into the brain of an elephant to kill him, and is destroyed at the same time; a wolf and a wolf-dog (the latter the wolf ’s own child, a creature that at once guards and devours sheep); a rapine ape; a vice-ridden woman, the wife of Cain; and finally the flesh of heretics like Mohammed and Martin Luther. Donne tells us that this soul lived “where every great change did come” (line 69), that it is something which both “did teare, / And mend the wracks of th’Empire” (lines 67–68), a principle of order and disorder both, or of order emerging out of disorder.1 For all its relentless powers

The Dream of the Moving Statue

Studies on the in~ath~a1 effect of endorphin in primate. T.L. Yaksh, K.E. Gross and Choh Hao Li (Departments of Neurosurgery and Pharmacology. Mayo Foundation, Rochester, Minn. 55905, U.S.A.), Brain Res., 241 (1982) 261-269. The intrathecal administration of /3-endorphin in the primate through an indweliing spinal catheter, produced a significant elevation in the nociceptive threshold as measured by the discrete trial shock titration task. The time of onset, duration of effect and magnitude of effect were all dose dependent over a range of 150750 pg. The effects were antagonized in a dose-dependent fashion by the systemic administration of naioxone. Aside from the elevations in the shock titration threshold produced by intrathecal ,&endorphin, no untoward effect on the animal’s motor function or behavioral reactivity was noted. There was no change in mean blood p0, and pCO,, heart rate and blood pressure measured immediately before and at 1, 3 and 6 h after intrathecal injection of /?-endorphin. The intrathecal administration was unaccompanied by any signs of irritation, agitation, retching or changes in pupil size. Significantly, unlike morphine, intrathecal ~-endo~hin failed to produce any signs of scratching behavior at the doses used in these experiments. Once daily administration of intrathecal /3-endorphin (500 pg) showed a significant progressive decline in the ~tinociceptive effect over an 8 day period. Animals made tolerant to /3-endorphin in this fashion showed a significantly reduced response to an otherwise active dose of intrathecal morphine, indicating evidence for cross-tolerance.