Al. Vaccarino et Lc. Couret, RELATIONSHIP BETWEEN HYPOTHALAMIC-PITUITARY-ADRENAL ACTIVITY AND BLOCKADE OF TOLERANCE TO MORPHINE ANALGESIA BY PAIN - A STRAIN COMPARISON, Pain, 63(3), 1995, pp. 385-389
We previously reported that morphine fails to produce analgesic tolera
nce when administered in the presence of formalin-induced pain. The hy
pothalamic-pituitary-adrenal (HPA) axis is known to respond to stressf
ul stimuli, including pain. To examine whether the blockade of toleran
ce by pain is related to HPA activity, we assessed the development of
tolerance to morphine analgesia in an inbred strain of rats that lack
typical stress-induced HPA responses (Lewis strain). Lewis rats lack t
ypical stress-induced activation of corticotropin-releasing hormone, a
drenocorticotropin hormone and glucocorticoids. Female Lewis rats were
injected with morphine (20 mg/kg, i.p.) or saline for 4 consecutive d
ays in the presence or absence of pain induced by injection of formali
n into the hind-paw. The analgesic effect of morphine (5, 10 or 20 mg/
kg, i.p.) was then measured in the tail-flick test 24 h after toleranc
e induction. Inbred female Fischer rats, which show significant stress
-induced HPA activity, were used for comparison. Analgesic tolerance w
as produced in both strains when morphine was delivered in the absence
of pain. However, the presence of pain during morphine administration
prevented the development of analgesic tolerance in Fischer, but not
in Lewis, rats. The differential effects of pain on the development of
tolerance to morphine analgesia are suggested to be related to geneti
cally determined differences in stress-induced HPA activity.