title: Induction of antinociceptive tolerance to the chronic intrathecal administration of apelin-13 in rat.
abstract: Pain represents a major contributing factor to the individual's quality of life. Although pain killers as opioids, endogenous or exogenous peptides can decrease pain perception, the chronic use of them leads to antinociceptive tolerance. It has been demonstrated that neuropeptide apelin has potent antinoceptive effect. However, the possibility of the induction of its antinociceptive tolerance has not yet been clarified. The tail-flick test was used to assess the nociceptive threshold. All experiments were carried out on male Wistar rats which received intrathecal apelin for 7days. To determine the role of apelin and opioid receptors on the development of apelin analgesic tolerance, their receptor antagonists (F-13 A and naloxone, respectively) were injected simultaneously with apelin. The lumbar spinal cord was assayed to determine apelin receptor levels by the western blotting method. Plasma corticosterone levels were assayed using ELISA. Results showed that apelin (3μg/rat) induced strong thermal antinociception. In addition, chronic apelin produced tolerance to its antinociceptive effect and down regulated spinal apelin receptor. F-13 A and naloxone could inhibit apelin tolerance development. The corticosterone levels did not change following drug administration. Taken together, the data indicated that apelin like other analgesic drugs leads to the induction of side effects such as analgesic tolerance which is mediated partly via the apelin and opioid receptors activation.
authors.affiliation: Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: elhamabbasloo6363@gmail.com.
authors.forename: Elham
authors.initials: E
authors.lastname: Abbasloo
authors.affiliation: Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Najafipour
authors.affiliation: Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Esmaeili-Mahani
mesh_terms: D000818:Animals; D000075244:Apelin Receptors; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007278:Injections, Spinal; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000075244:Apelin Receptors; C491284:Aplnr protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D009292:Narcotic Antagonists; D043562:Receptors, G-Protein-Coupled; D011957:Receptors, Opioid; C495199:apelin-13 peptide; C532492:apelin-13, Ala(13)-; D009270:Naloxone
keywords: Antinociception; Apelin; Opioid receptors; Tolerance