Minocycline through attenuation of oxidative stress and inflammatory response reduces the neuropathic pain in a rat model of chronic constriction injury

Abstract

Objectives: Several lines of evidence showed that minocycline possesses antioxidant and anti-inflammatory properties. This study aimed to demonstrate the effects of minocycline in rats subjected to chronic constriction injury (CCI).

Materials and methods: In this study four groups (n = 6-8) of rats were used as follows: Sham, CCI, CCI + minocycline (MIN) 10 mg/Kg (IP) and CCI + MIN 30 mg/Kg (IP). On days 3, 7, 14, and 21 post-surgery hot-plate, acetone, and von Frey tests were carried out. Finally, Motor Nerve Conduction Velocity Evaluation (MNCV) assessment was performed and spinal cords were harvested in order to measure tissue concentrations of TNF_α, IL-1β, Glutathione peroxidase (GPx), Superoxide dismutase (SOD) and Malondialdehyde (MDA). Extent of perineural inflammation and damage around the sciatic nerve was histopathologically evaluated.

Results: Our results demonstrated that CCI significantly caused hyperalgesia and allodynia twenty-one days after CCI. MIN attenuated heat hyperalgesia, cold and mechanical allodynia and MNCV in animals. MIN also decreased the levels of TNF_α and IL-1β. Antioxidative enzymes (SOD, MDA, and GPx) were restored following MIN treatment. Our findings showed that MIN decreased perineural inflammation around the sciatic nerve. According to the results, the neuropathic pain reduced in the CCI hyperalgesia model using 30 mg/kg of minocycline.

Conclusion: It is suggested that antinociceptive effects of minocycline might be mediated through the inhibition of inflammatory response and attenuation of oxidative stress.

Keywords: Chronic constriction; Inflammatory response; Injury; Minocycline; Neuropathic pain; Oxidative stress; Rat.

Figure 1

The effect of minocycline administration on CCI-induced heat hyperalgesia, assessed using the hot-plate test. Rats were treated with vehicle or minocycline at doses of 10 and 30 mg/kg once daily for a period of 21 days. The data were shown as mean ± SEM. ** P< 0.01 vs Sham, ***P< 0.001 vs Sham, ^#P< 0.05 vs CCI, ## P< 0.01 vs CCI, and ### P< 0.001 vs CCI

Figure 2

The effects of minocycline administration on CCI- induced cold allodynia assessed using the acetone test. Rats were treated with vehicle or minocycline at doses of 10 and 30 mg/kg once daily for a period of 21 days. The data were shown as mean ± SEM. *** P< 0.001 vs Sham, ^# P< 0.05 vs CCI, and ^### P< 0.001 vs CCI

Figure 3

The effects of minocycline administration on CCI-induced mechanical allodynia assessed using the von Frey test. Rats were treated with vehicle or minocycline at doses of 10 and 30 mg/kg once daily for a period of 21 days. The data were shown as mean ± SEM. ** P< 0.01 vs Sham, *** P< 0.001 vs Sham, and ^### P< 0.001 vs CCI

Figure 4

The effects of minocycline administration on MNCV in the sciatic nerve. Rats were treated with vehicle or minocycline at doses of 10 and 30 mg/kg once daily for a period of 21 days. The data were shown as mean ± SEM; *** P< 0.001 vs Sham, ^# P< 0.05 vs CCI, and ^### P< 0.001 vs CCI

Figure 5

The effects of minocycline administration on IL-1β and TNF-α in the spinal nerve. Rats were treated with vehicle or minocycline at doses of 10 and 30 mg/kg once daily for a period of 21 days. The data were shown as mean ± SEM; *** P< 0.001 vs Sham, ^# P< 0.05 vs CCI, and ^### P< 0.001 vs CCI

Figure 6

The effects of minocycline administration on MDA, SOD, and GPx levels in the spinal nerve. Rats were treated with vehicle or minocycline at doses of 10 and 30 mg/kg once daily for a period of 21 days. The data were shown as mean ± SEM, *** P< 0.001 vs Sham, ^# P< 0.05 vs CCI, ^## P< 0.01 vs CCI, and ^### P< 0.001 vs CCI

Figure 7

Histological and morphological studies in the sciatic nerve at 21 days after CCI induction. In untreated CCI rats, the sciatic nerve has diffuse areas of moderate to marked edema/cellular infiltrate. In the MIN-treated (30 mg/kg) CCI rats, the finding is small focal areas of mild edema and/or cellular infiltrate