Synergistic effect of spexin and progesterone on pain sensitivity attenuation in ovariectomized rats

Abstract

Spexin is a central modulator of nociception. The aim of the present study was to investigate the effect of intra-hippocampal CA3 (IHCA3) injection of spexin and spexin-progesterone co-administration on pain sensitivity in ovariectomized rat. Thirty-five adult female rats were divided into five groups. Sham: the animals received injection of 0.5 μL ACSF by IHCA3. Experiments 1 and 2: the animals received injection of 0.5 μL of spexin bilaterally (10 and 30 nmol/rat respectively). Experiments 3 and 4: the animals received injection of 0.5 μL of spexin bilaterally (10 and 30 nmol/rat respectively) + subcutaneous (s.c.) injection of progesterone (5 mg/kg). Ovariectomy was performed in all groups to eliminate the effects of cyclic changes in the female rats. The formalin test (formalin 2.5%) was performed following the administration of spexin and progesterone. Results showed that bilateral injection of spexin in IHCA3 at both concentrations a significant (P < .05) decrease in the pain sensitivity in the two phases of formalin test. Similarly, the bilateral injection of spexin in IHCA3 at both concentrations following the s.c. injection of progesterone significantly (P < .05) decreases pain sensitivity in two phases of the formalin test. This pain attenuation due to the co-administration of spexin and progesterone was more potent than spexin-induced analgesia. According to the present results, spexin has a modulatory effect on pain sensitivity, which becomes more pronounced by progesterone administration.

Emerging Roles of NPQ/Spexin in Physiology and Pathology

“…Female rats injected with spexin in hippocampal CA1 show a decrease in pain sensitivity in the formalin test, indicating an analgesic effect on tonic pain (Pirzeh and Taherianfard, 2014). Intra hippocampal CA3 (IHCA3) administration of spexin inhibited the pain sensitivity in the both early and late phrases of the rat formalin test (Moazen et al., 2017). Lv et al.…”

Mouse Spexin: (II) Functional Role as a Satiety Factor inhibiting Food Intake by Regulatory Actions Within the Hypothalamus

“…Its mature peptide is highly conserved with only 1 to 2 a.a. substitutions from fish to mammals (3,4). It is widely expressed in different tissues, including the liver, pancreas, visceral fat, intestine, and adrenal gland, e.g., in the rat (5) and human (6), and reported to have regulatory actions on gut motility (7), stomach contraction (1), bile acid synthesis (8), food consumption (9,10), glucose and lipid homeostasis (11,12), fatty acid uptake (13,14), hormone secretion (15,16), locomotor activity (14), nociception (17,18), stress/anxiety responses (19), and cardiovascular/renal functions (20). In human, SPX is encoded by the gene c12orf39 located in chromosome 12 (21) and abnormalities in SPX expression/serum levels can be associated with childhood (22,23) and adult obesity (24), type I/II diabetes (6,25), gestational diabetes (26), metabolic syndrome (27), cardiovascular disease (28), and psychiatric disorders including anorexia nervosa (29) and anxiety/ depression (30,31).…”

Circulating Spexin Levels Negatively Correlate With Age, BMI, Fasting Glucose, and Triglycerides in Healthy Adult Women

“…Expressed centrally and peripherally [ 4–7 ], spexin has been implicated in the regulation of satiety/food intake [ 8–12 ], gastrointestinal motility [ 1 , 13 ], energy metabolism [ 12 ], and glucose/lipid metabolism [ 7 ]. It has also been suggested as a role in the control of adrenocortical cell proliferation [ 5 ], cardiovascular and renal function [ 14 ], endocrine [ 15 ], nociception [ 14 , 16 ], and reproduction [ 15 ]. Spexin has been related to a number of human disorders, including obesity [ 17–22 ], type 2 diabetes mellitus (T2DM) [ 7 , 19 ], fatty liver disease [ 19 , 23 ], constipation [ 13 ], anxiety [ 24 , 25 ], and depression [ 26 ].…”