hemopressin and Pain

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

Endogenous hemorphins, derived from degradation of the beta-chain of hemoglobin, lower arterial blood pressure and exert an antinociceptive action in experimental models of nociception. Hemopressin, derived from the alpha-chain of hemoglobin, also decreases blood pressure, but its effects on pain have not been studied. In this work, we examined the influence of hemopressin on inflammatory pain. Hemopressin reverted the hyperalgesia induced by either carrageenin or bradykinin when injected concomitantly or 2.5 h after the phlogistic agents. Hemopressin administered systemically also reverted the hyperalgesia induced by carrageenin. Naloxone did not prevent the antinociceptive action of this peptide. These data suggest that hemopressin inhibits peripheral hyperalgesic responses by mechanisms independent of opioid receptor activation.

Topics: Analgesics; Animals; Blood Pressure; Bradykinin; Carrageenan; Disease Models, Animal; Endorphins; Hemoglobins; Hyperalgesia; Inflammation; Male; Naloxone; Narcotic Antagonists; Pain; Pain Measurement; Peptide Fragments; Peptides; Rats; Rats, Wistar; Receptors, Opioid; Time Factors