Biphasic modulation of visceral nociception by neurotensin in rat rostral ventromedial medulla

A potential role for neurotensin in the rostral ventromedial medulla (RVM) in modulation of Visceral nociceptive transmission was examined in this stu dy. Microinjection of neurotensin (3-3000 pmol) into the RVM of awake rats produced a dose-dependent inhibition of the visceromotor response (VMR) to noxious colorectal distension (CRD) that tasted 30 to 120 min. Additionally , intra-RVM injection of neurotensin (300 pmol) significantly reduced the s lope of the stimulus-response function to graded CRD (20-80 mm Hg), whereas the greatest dose of neurotensin (3000 pmol) completely inhibited the VMR at all intensities of CRD. General motor function was unaffected after intr a-RVM injection of neurotensin (3000 pmol). Intra-RVM injection of lesser d oses of neurotensin (0.03-0.30 pmol) resulted an enhancement of the VMR to noxious CRD that had a short duration (18-30 min), and produced a leftward shift of the stimulus-response function to graded CRD without a change in t he slope of the function. Additionally, intra-RVM injection of the neuroten sin-receptor antagonist SR48692 (0.3-300 fmol) in naive animals produced do se-dependent inhibition of VMR to noxious CRD, whereas a lesser dose (0.03 fmol) enhanced the VMR. These data support a role for neurotensin in the RV M in biphasic modulation of visceral nociception. The results obtained with SR48692 suggest that endogenous neurotensin in the RVM modulates VMR to no xious CRD via a prominent interaction with neurotensin receptors that media te facilitatory influences and a lesser interaction with neurotensin recept ors that mediate masked inhibitory influences.