One by one scientists set up the pain cascade of chemicals and attempt to knock them off.
Bredeloux et al in J Med Chem. 2008 Mar 6 report that an analogue of neurotensin; namely c(Lys-Lys-Pro-Tyr-Ile-Leu-Lys-Lys-Pro-Tyr-Ile-Leu) (JMV2012) penetrates the blood brain barrier and causes profound analgesia. This drug can be administered peripherally, unlike Prialt (ziconotide), which is given into the spinal fluid. It is somewhat unexpected given that neurotensin injected into the hypothalamic paraventtricular nucleus does not affect pain threshold.(see Yang et al Neuropeptides Jun 07); whereas arginine vasopressin injected into the PVN DOES cause antinociception.
However Roussy has shown that neurotension I injected into the spine and supraspinally does cause antinociception, so we must set the PVN aside for now, concluding that different mechanisms are at work in the ventricles to compared to the surrounding area. J. Neurochemi Jan 22 2008).
Ventricles are spaces in the brain, in which cerebrospinal fluid circulates. Dobner in Peptides Oct 2006 DID show marked antinociception from NT into the periAQUEDUCTAL grey. The cerebral aqueduct is a small canal in the midbrain measuring about 3/4 inch, which connects the third and fourth ventricles.
In 2006 Bredeloux showed (Behav Brain Res Dec) that injecting neurotensin INTO the ventricles had fairly potent pain suppression, which these researchers concluded was linked to the opioid system. There is also evidence that neurotensin II can do the same thing. (See also Sarrett J Neurosci Sept 2005)
It is not an absolute breakthrough since the competitive neurotensin compound also causes severe hypothermia. It is touchy trying to stop nerve activity without having undesiable side effects. Still, most cells have unique receptors, and it is usually only a matter of tiem before a drug can be idnetified which blocks one receptor without blocking another.