Asprosin, a novel therapeutic candidate for painful neuropathy: an experimental study in mice.

Sibel Ozcan,Muhammed Mirac Kelestemur,Munevver Gizem Hekim,Ozgur Bulmus,Mete Ozcan,Batuhan Bilgin,Ferah Bulut,Sinan Canpolat

doi:10.1007/s00210-021-02197-w

Sibel Ozcan, Muhammed Mirac Kelestemur + Show 6 more

Open Access

https://doi.org/10.1007/s00210-021-02197-w

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Abstract

Recent studies indicate presence of a strong link between adipokines and neuropathic pain. However, the effects of asprosin, a novel adipokine, on neuropathic pain have not been studied in animal models.Mouse models were employed to investigate the antinociceptive effectiveness of asprosin in the treatment of three types of neuropathic pain, with metabolic (streptozocin/STZ), toxic (oxaliplatin/OXA), and traumatic (sciatic nerve ligation/CCI [chronic constriction nerve injury]) etiologies, respectively. Changes in nociceptive behaviors were assessed relative to controls using thermal (the hot plate and cold plate tests, at 50°C and 4°C respectively) and mechanical pain (von Frey test) tests after intraperitoneal (i.p.) administration of asprosin (10µg/kg) and gabapentin (50mg/kg) in several times intervals. Besides, possible effect of asprosin on the motor coordination of mice was assessed with a rotarod test. Serum level of asprosin was quantified by ELISA.In neuropathic pain models (STZ, OXA, and CCI), asprosin administration significantly reduced both mechanical and thermal hypersensitivity, indicating that it exhibits a clear-cut antihypersensitivity effect in the analyzed neuropathic pain models. The most effective time of asprosin on pain threshold was observed 60min after its injection. Also, asprosin displayed no notable effect on the motor activity. Asprosin levels were significantly lower in neuropathic pain compared to healthy group (p < 0.05).The results yielded by the present study suggest that asprosin exhibits an analgesic effect in the neuropathic pain models and may have clinical utility in alleviating chronic pain associated with disease and injury originating from peripheral structures.

Highlights

Neuropathic pain is a severe pathology of the nervous system that offers no adaptable benefit
The findings revealed that asprosin level decreased in animals with neuropathic pain, as 30.5±7.1 ng/mL was obtained for animals with type 1 diabetes, 23.1±7.3 ng/mL for animals with neuropathy after OXA use, and 22.0±6.9 ng/mL for animals with neuropathy after constriction injury (CCI) (Figure 7)
The findings yielded by the present study indicate that asprosin administration significantly reduced mechanical and thermal hypersensitivity in mouse models for different painful neuropathies

Summary

Introduction

Neuropathic pain is a severe pathology of the nervous system that offers no adaptable benefit. Administration of asprosin increases blood glucose levels in healthy mice (Romere et al, 2016), but has no effects on diabetic mice (Hekim et al, 2021). Prior investigations further indicate that plasma asprosin crosses the blood-brain barrier and activates orexigenic AMP-dependent-aqouti-related neuropeptide (AgRP) neurons in hypothalamus. This signaling results in inhibition of anorexigenic pre-opiomelanocortin (POMC) neurons in a GABA-dependent manner (Greenhill, 2016, Duerrschmid et al, 2017, Beutler and Knight, 2018, Li et al, 2018, Ozcan et al, 2020). The effects of glycogenic hormone asprosin on neuropathic pain that cause hyperalgesia in mice models are unknown

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