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: 10 μl, intrathecally) and two subgroups with intrathecal injection (i.t) of 1 μg and 5 μg 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 8 weeks. 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 (1 μg and 5 μg) 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.