endomorphin-2 and hemopressin

It is well known that a multitude of ligands and receptors are involved in the nociceptive system, and some of them increase, while others inhibit the pain sensation both peripherally and centrally. These substances, including neurotransmitters, neuromodulators, hormones, cytokines etc., may modify the activity of nerves involved in the pain pathways. It is also well known that the organism can express very effective antinociception in different circumstances, and during such situations the levels of various endogenous ligands change. Accordingly, a very exciting field of pain research relates to the roles of endogenous ligands. The peripheral action may possibly be extremely important, because low doses of the endogenous ligands may reduce pain without disphoric side-effects, and without the abused potential typical of centrally acting ligands. This review provides a comprehensive overview of the endogenous ligands that can induce antinociception, discusses their effects on different receptors and focuses on their action at peripheral level. We found 17 different endogenous ligands which produced antinociception after their topical administration. The results suggest an important direction for the development of pain strategies that focus on the local administrations of different endogenous ligands.

Topics: Analgesics, Opioid; Animals; Annexin A1; beta-Endorphin; Cytokines; Endorphins; Excitatory Amino Acid Agents; Hemoglobins; Kynurenic Acid; Ligands; Lipid Metabolism; Melatonin; Mice; Neuropeptides; Neurotransmitter Agents; Nociceptin; Oligopeptides; Opioid Peptides; Pain; Pain Measurement; Pain Threshold; Peptide Fragments; Peripheral Nervous System; Pituitary Adenylate Cyclase-Activating Polypeptide; Rats; Somatostatin