Chronic administration of [Pyr1] apelin-13 attenuates neuropathic pain after compression spinal cord injury in rats.
Apelin is an endogenous ligand for apelin receptor (APJ) with analgesic effect on visceral, analgesic and proanalgesic influences on acute pains in animal models. The purpose of this study was to determine the possible analgesic effects of [Pyr1] apelin-13 on chronic pain after spinal cord injury (SCI) in rats. Animals were randomly divided into three major groups as intact, sham and SCI. The SCI group randomly allocated to four subgroups as no treatment, vehicle-treatment (normal saline: 10μl, intrathecally) and two subgroups with intrathecal injection (i.t) of 1μg and 5μg of [Pyr1] apelin-13. After laminectomy at T6-T8 level, spinal cord compression injury was induced using an aneurysm clip. Vehicle or [Pyr1] apelin-13 injected from day1 post SCI and continued for a week on a daily basis. Pain behaviors and locomotor activity were monitored up to 8weeks. At the end of the experiments, intracardial paraformaldehyde perfusion was made under deep anesthesia in some animals for histological and immunohistochemistry evaluations. Western blot technique was also done to detect caspase-3 in fresh spinal cord tissues. SCI decreased nociceptive thresholds and locomotor scores. Administration of [Pyr1] apelin-13 (1μg and 5μg) improved locomotor activity and reduced pain symptoms, cavity size and caspase-3 levels. Results showed long-term beneficial effects of [Pyr1] apelin-13 on neuropathic pain and locomotion. Therefore, we may suggest [Pyr1] apelin-13 as a new option for further neuropathic pain research and a suitable candidate for ensuing clinical trials in spinal cord injury arena.
Department of Physiology, Tehran University of Medical Sciences, Tehran, Iran.
Zahra
Z
Hajimashhadi
Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Physiology, Medical School, Iran University of Medical Sciences, Tehran, Iran.
Nahid
N
Aboutaleb
Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Physiology, Medical School, Iran University of Medical Sciences, Tehran, Iran. Electronic address: nasirinezhad.f@iums.ac.ir.
Farinaz
F
Nasirinezhad
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects*; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013117:Spinal Cord Compression / Q000150:complications* / Q000378:metabolism
D000700:Analgesics; D036341:Intercellular Signaling Peptides and Proteins; C495199:apelin-13 peptide; D053148:Caspase 3
Apoptosis; Compression spinal cord injury; Neuropathic pain; [Pyr(1)] apelin-13