beta-Endorphin: behavioral and analgesic activity in cats.

Abstract

fl-fEndorphin has been.shown to possess potent behavioral and antinociceptive activities when administered intraventricularly in cats. On a molar.basis, P-endorphin is times more ptent than morphine and its actions are blocked by the speciricopiate antagonist, naloxone.(3-Endorphin, an untriakontapeptide isolated from camel pituitary glands (1), has been synthesized (2) and shown to possess opiate-like activity in receptor binding assays and in the guinea pig ileum bioassay (1-3). The analgesic activity of the synthetic peptide has been tested in rodents by intracerebral injection and found to be 18-33 times more potent than morphine, when compared on a molar basis, as shown by the tail-flick test, the hot plate test, and the acetic acid-induced writhing method in mice and the ice water-induced shake response in rats (4). In addition, fl-endorphin has also been tested in mice via intravenous administration and found to be 3-4 times more potent than morphine, on a molar basis, in its analgesic effect (5). The present study was undertaken to determine the analgesic and behavioral effects of the peptide administered intraventricularly in the awake, unrestrained cat. showed an alteration of their behavior as follows: (I) fine tremors of the head accompanied by sudden quick head movements; MATERIALS AND METHODS Met(ii) mild excitation; (fii) fixation of eyes into space or on an object (cats barely responded to external noises-shaing of the cage, tapping of the floor, calling, etc.-and were hardly distracted from their apparent fixation on phantom objects; they changed their direction of gaze from time to time, but they always appeared to have "visual hallucinations"); and (iv) pupillary dilatation varied in intensity from one cat to the other, although fixation of eyes into space was prominent in all cats tested. The altered behavior was evident for about 1 hr, after which the animals appeared to return to their normal behavioral state. In none of the animals was intravenrtricular injection of 12.5 MAg of (3-endorphin followed by a significant alteration in JOR or response to pinch test.Intraventricular injection of 25MAg of fl-endorphin induced, within 15-20 min, alteration of behavior in all cats as described above. In general, the alterations were somewhat more pronounced and. longer lasting than those seen after adminiation of 12.5 Mug of the peptide. In all animals the intraventricular administration of (3-endorphin was followed by a significant rise of the threshold for the JOR. Such an increase in threshold was always concomitant with or came after the first signs of behavioral change. The maximal increase of the JOR threshold was reached about 60 min after peptide administration (Fig.

Presence of a reduced opioid response in interleukin‐6 knock out mice

“…The finding that the lack of IL‐6 induces an alteration in the analgesic responses to morphine administration raises the question as to whether this condition is associated with changes in the synthesis of neuropeptides involved in the modulation of pain sensitivity and in morphine‐induced analgesia. Many studies in this field have demonstrated that the opioid peptide BE is able to enhance nociceptive thresholds and to affect the analgesic response to morphine administration in animals (Meglio et al . 1977; Jacquet 1978; Panerai et al .…”

Presence of immunoreactive beta-endorphin in normal human plasma: a concomitant release of beta-endorphin with adrenocorticotropin after metyrapone administration.

“…Among these, f8-endorphin, which corresponds to 61-91 amino acids of f8-lipotropin (,3-LPH),1 is the most potent in analgesic activity (4), opiate receptor binding (5), and behavioral effect (6). However, the physiological role of ,f-endorphin is still unknown.…”

beta-Endorphin: development of tolerance and its reversal by 5-hydroxytryptophan in cats.

“…through this cannula in awake, unrestrained cats. The extent of analgesia was determined by stimulating tooth pulp and measuring the jaw opening reflex (JOR) as described (3). The degree of analgesia or its absence was also tested by pinches applied with a small hemostat or tooth forceps to the cat's tail, limbs, and ears.…”

“…The analgesic effect is accompanied by "hallucinatory" behavioral alterations (3). On a molar basis, f3-endorphin is 72-96 times more potent than morphine and its activity is blocked by naloxone (3). Earlier observations in cats (3) and in rodents (5,6) indicated that repeated injections of the peptide result in the development of acute tolerance as well as cross-tolerance to morphine.…”

“…(3,4) in cats. The analgesic effect is accompanied by "hallucinatory" behavioral alterations (3). On a molar basis, f3-endorphin is 72-96 times more potent than morphine and its activity is blocked by naloxone (3).…”