Intrathecally Administered Apelin-13 Alleviated Complete Freund’s Adjuvant-Induced Inflammatory Pain in Mice

Abstract

Apelin is the endogenous ligand for APJ, a G-protein-coupled receptor. Apelin gene and protein are widely distributed in the central nervous system and peripheral tissues. The role of apelin in chronic inflammatory pain is still unclear. In the present study, a mouse model of complete Freund’s adjuvant (CFA)-induced inflammatory pain was utilized, and the paw withdrawal latency/threshold in response to thermal stimulation and Von Frey filament stimulation were recorded after intrathecal (i.t.) injection of apelin-13 (0.1, 1, and 10 nmol/mouse). The mRNA and protein expression, concentration of glutamic acid (Glu), and number of c-Fos immunol staining in lumbar spinal cord (L4/5) were determined. The results demonstrated that Apln gene expression in the lumbar spinal cord was down-regulated in the CFA pain model. Apelin-13 (10 nmol/mouse, i.t.) alleviated CFA-induced inflammatory pain, and it exhibited a more potent antinociceptive effect than apelin-36 and (pyr)apelin-13. The antinociception of apelin-13 could be blocked by APJ antagonist apelin-13(F13A). I.T. apelin-13 attenuated the increased levels of Aplnr , Grin2b, Camk2d , and c-Fos genes expression, Glu concentration, and NMDA receptor 2B (GluN2B) protein expression caused by CFA. Apelin-13 significantly reduced the number of Fos-positive cells in laminae III and IV/V of the dorsal horn. This study indicated that i.t. apelin-13 exerted an analgesic effect against inflammatory pain, which was mediated by activation of APJ, and inhibition of Glu/GluN2B function and neural activity of the spinal dorsal horn.

Physiological Changes and Pathological Pain Associated with Sedentary Lifestyle-Induced Body Systems Fat Accumulation and Their Modulation by Physical Exercise

“…As for apelin, peripheral injection of a single dose causes thermal hyperalgesia [478], but its intrathecal administration alleviates CFA-induced thermal and mechanical hypersensitivity in mice [479]. In models of formalin-induced pathological pain, intravenous injection of apelin reduces pain response during the second phase of the mouse formalin test, whereas intramuscular injection of apelin reduces licking/biting time during the second phase only at higher dose.…”

Apelin/APJ system: an emerging therapeutic target for neurological diseases

“…For inflammatory pain, the existing findings indicate that in the experiment of electroacupuncture stimulation to relieve inflammatory pain, the transcription and expression of the apelin/APJ system are significantly improved [ 99 ]. Attractively, Lv et al have concretely elaborated the mechanism of apelin attenuating inflammatory pain [ 100 , 101 ].…”

Effects of Electroacupuncture on Alleviating Prostatodynia and Inflammation in Rats with Chronic Nonbacterial Prostatitis

“…24 Paw Withdrawal Threshold Paw withdrawal threshold (PWT) was tested every seven days using the Semmes-Weinstein von Frey Touch Test Sensory Evaluator (North Coast Medical Inc.), as previously described. 25,26 Specifically, rats were placed in a plexiglass cage with a metal mesh at the bottom. After 5 minutes of adaptation, they were stimulated by von Frey hairs to make the cilia bend until the rats showed the foot retraction reflex.…”