A research team, headed by ZHANG Xu, a research fellow working for the Institute of Neuroscience under the Shanghai Institutes for Biological Sciences, part of the Chinese Academy of Sciences, found that preprotachykinin is a key molecule directly involving in modulation of pain transmission in the spinal cord. Reported in a recent issue of journal Cell, the finding makes a breakthrough challenging the traditional roles of the substance P and opioid analgesia.
Researchers found that the direct interaction between protachykinin and |?-opioid receptors (DORs) is responsible for sorting of DORs into large dense-core vesicles (LDCVs), allowing stimulus-induced surface insertion of DORs and DOR-mediated spinal analgesia.
Further study also revealed that a rat depleted with the preprotachykinin A gene reduced stimulus-induced surface insertion of DORs and abolished DOR-mediated spinal analgesia and morphine tolerance. As a result, the rat produced no morphine tolerance, which means the painkilling effects of morphines will not be reduced when painkillers are used in a protracted period of time. The finding, with a conclusion that protachykinin is essential for modulation of the sensitivity of nociceptive afferents to opioids, creates a new theoretical basis for developing new painkillers. |
