Methods for manipulating upper gastrointestinal transit, blood flow, and satiety, and for treating visceral hyperalgesia

A method of manipulating satiety in a mammalian subject having a cholinergic afferent neural pathway projecting from a peptide YY-sensitive primary sensory neuron in the intestinal wall to a prevertebral celiac ganglion and having an adrenergic efferent neural pathway projecting from said ganglion to one or more enterochromaffin cells in the intestinal mucosa and/or to a serotonergic intemeuron linked in amyenteric plexus to an opioid intemeuron, said opioid interneuron also being linked by an intestino-fugal opioid pathway projecting to said ganglion, with one or more neural connections to the central nervous system and back to the gut projecting from the ganglion, said method comprising:

• providing a pharmaceutically acceptable composition, comprising an active agent selected from the group consisting of
• (A) peptide YY, and
• (B) antagonists of receptors for (A);
• and
• administering the pharmaceutically acceptable composition to the mammal,
• said active agent being delivered in an amount and under conditions such that the cholinergic intestino-fugal pathway, one or more prevertebral ganglionic pathways, adrenergic efferent neural pathway, the serotonergic interneuron and/or the opioid intemeuron are activated by the action of (A), whereby a state of satiety is induced, or such that activation of the cholinergic intestino-fugal pathway, prevertebral ganglionic pathways, ganglion to central nervous system pathways, central nervous system pathways, adrenergic efferent neural pathway, the serotonergic intemeuron and/or the opioid interneuron is blocked by the action of (B), whereby satiety is suppressed.

A method of inducing satiety in a mammal having an intrinsic cholinergic afferent neural pathway projecting from a peptide YY-sensitive primary sensory neuron in the intestinal wall to a prevertebral celiac ganglion and having a adrenergic efferent neural pathway projecting from said ganglion to one or more enterochromaffin cells in the intestinal mucosa and/or to a serotonergic intemeuron linked in a myenteric plexus and/or submucous plexus to an opioid intemeuron, said opioid intemeuron also being linked by anintestino-fugal opioid pathway projecting to said ganglion, with one or more neural connections to the central nervous system and back to the gut projecting from the ganglion, said method comprising:

• providing a pharmaceutically acceptable composition, comprising peptide YY;
• and
• administering the pharmaceutically acceptable composition to the mammal,
• said peptide YY being delivered in an amount and under conditions such that the cholinergic intestino-fugal pathway, prevertebral ganglionic pathways, ganglion to central nervous system pathways, adrenergic efferent neural pathway, the serotonergic intemeuron and/or the opioid interneuron are activated by the action of said peptide YY, whereby a state of satiety is induced in the mammal.

A method of treating visceral pain or visceral hypersensitivity in a human subject having a cholinergic afferent neural pathway projecting from a peptide YY-sensitive primary sensory neuron in the intestinal wall to a prevertebral celiac ganglion and having a adrenergic efferent neural pathway projecting from said ganglion to one or more enterochromaffin cells in the intestinal mucosa and/or to a serotonergic interneuron linked in a myenteric plexus to an opioid intemeuron, said opioid intemeuron also being linked by an intestino-fugal opioid pathway projecting to said ganglion, with one or more neural connections to the central nervous system and back to the gut projecting from the ganglion, said method comprising:

• providing a pharmaceutically acceptable composition, comprising peptide YY;
• and
• administering the pharmaceutically acceptable composition to the mammal,
• said peptide YY being delivered in an amount and under conditions such that activation of a cholinergic intestino-fugal pathway, one or more prevertebral ganglionic pathways, a gangalion to central nervous system pathway, the adrenergic efferent neural pathway, the serotonergic intemeuron and/or the opioid intemeuron is substantially reduced by the action of said peptide YY, whereby the sensation of esophageal, gastric, biliary, intestinal, colonic or rectal pain experienced by the human subject is reduced.

A method of manipulating post-prandial visceral blood flow to the gastrointestinal tract of a mammal having a cholinergic afferent neural pathway projecting from a peptide YY-sensitive primary sensory neuron in the intestinal wall to a prevertebral celiac ganglion and having an adrenergic efferent neural pathway projecting from said ganglion to one or more enterochromaffin cells in the intestinal mucosa and/or to a serotonergic intemeuron linked in a myenteric plexus to an opioid intemeuron, said opioid intemeuron also being linked by an intestino-fugal opioid pathway projecting to said ganglion, with additional neural connections to the central nervous system and back to the gut projecting from the ganglion, comprising:

• providing a pharmaceutically acceptable composition, comprising an active agent selected from the group consisting of
• (A) peptide YY, and
• (B) antagonists of receptors for (A);
• and
• administering the pharmaceutically acceptable composition to the mammal,
• said active agent being delivered in an amount and under conditions such that the cholinergic intestino-fugal pathway, prevertebral ganglionic pathways, gangalion to central nervous system pathways, central nervous system pathways, adrenergic efferent neural pathway, the serotonergic interneuron and/or the opioid intemeuron are activated by the action of (A), whereby the flow of blood to the gastrointestinal tract is increased, or such that activation of the cholinergic intestino-fugal pathway, prevertebral ganglionic pathways, gangalion to central nervous system pathways, the adrenergic efferent neural pathway, the serotonergic intemeuron and/or the opioid intemeuron is blocked by the action of (B), whereby the flow of blood to the gastrointestinal tract is decreased.