Neuropeptides and spinal antinociception : Studies on galanin, nociceptin and endomorphin

摘要: Nociception and/or the sensation of pain is essential for survival organism. Just as important are antinociceptive mechanisms that reduce nociceptive input and perceived pain. Without such mechanisms, it would be impossible to turn one’s focus away from even most minor painful stimulus. The balance between excitatory inhibitory functions in nociception intricate complex some modulators involved may future drug development treating states. This work has tried highlight neuropeptides endogenous mechanism. Endomorphin-1 endomorphin-2 peptides have high selectivity affinity μ-opioid receptor, receptor mediating effect morphine. Intrathecal (i.t.) application endomorphin-1 –2 produced a dose-dependent short lasting depression spinal flexor reflex normal rats with comparable potency. was significantly longer than endomorphin-2, suggesting possible difference enzymatic degradation. depressive maintained after inflammation axotomized did not exhibit neuropathic pain-like behavior (autotomy). However, exhibiting autotomy nerve section, reduced. These results suggest presence decreases potency which similar what observed Nociceptin/orphanin FQ ligand orphan opioid-receptor-like (ORL1). We now verified nociceptin analogue [Nphe1]nociceptin(1-13)NH2 selective antagonist rat cord. also systematically evaluated i.t. on normal, inflamed injured rats. It reduced if anything increased injury. showed agonists useful analgesics Galanin well documented peptide nociception. presented this thesis provides further evidence an role inflammation. Moreover, we developed protocol study mice studies over-expressing galanin suggested level effective hyperexcitability repetitive C-fiber stimulation. obtain GAL-R1 tonically inhibiting under condition lacking receptor.