Supraspinal cerebral areas involved in morphine's intestinal inhibition and analgesia

To explore the neuroanatomical pathways involved in mediating the antipropulsive effect and analgesia of morphine (M) in the periaqueductal gray matter (PAG), we examined the influence of the vagus nerve and the role of serotonergic neurotransmission. M-induced inhibition of intestinal transit was unaffected by subdiaphragmatic vagotomy. In contrast, electrolytic lesions in the raphe magnus nucleus (NRM) and pretreatment with a selective neurotoxin (5,6-DHT, 15 micrograms/rat) in the same region, both significantly reduced M-induced inhibition of intestinal transit. Analgesia was only slightly affected. p-CPA pretreatment (100 mg/kg IP) induced the same results. Finally some other central brain regions were found to be sensitive to M's intestinal inhibition and analgesia such as the mid-line thalamus, the dorsal and lateral hypothalamus, and the bulbar reticular formation. Negative results were obtained for frontal cortex, caudate and amygdala. Some considerations are put forward about the existence in the central nervous system of selective areas involved in intestinal modulation and their relation with those mediating pain transmission.