Evaluation of the analgesic effect of morphine on models of acute nociceptive pain in rats with a central noradrenergic system lesion

OBJECTIVES: Stimulation of some noradrenergic system receptors demonstrates a synergistic anti-nociceptive effect with the opioid system at the level of peripheral tissues, spinal cord, and supraspinal structures. Furthermore, opioids stimulate the noradrenergic descending pathways originating from the substantia nigra by presynaptic inhibition of the GABA neuron ends. It is thus important to determine whether a disruption to the adrenergic transmission obtained via DPS-4 administration to neonatal rats impacts the perception of noxious stimuli mediated by 5-HT3-serotonin receptors at the level of spinal cords or higher tiers of the central nervous system. DESIGN & SETTING: The studies were conducted with neonatal and adult rats, males of the Wistar strain in which a central noradrenergic system lesion was induced with DSP-4 on days 1 and 3 of life. Next, the evaluation of the analgesic effect of morphine was performed on 8- to 10-week-old animals using the following models of acute nociceptive pain: the hot plate test and the tail immersion test as models of acute nociceptive pain induced by a thermal stimulus, and the paw withdrawal test as a model of nociceptive pain caused by a mechanical stimulus. RESULTS: Morphine was found to produce a longer-lasting analgesic effect in the tail immersion test in the control group than in rats. Similarly, in the paw withdrawal test, this substance generated a strong analgesic effect ( with over 200% of analgesia) in the control group, whereas its action in the rats with DSP-4 lesions was statistically significant. Morphine induced analgesia at about 13-14% in the control rats when examined with the hot plate test. CONCLUSIONS: The disruption to the central noradrenergic system in an early stage of development resulted in a reduction of the analgesic effect of morphine in the models of acute pain in which the mechanisms of supraspinal perception are involved.