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

Document Type: Original Article


1 Department of Surgery, Lorestan University of Medical Sciences, Khorramabad, Iran

2 2Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran

3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran

4 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

5 Nutritional Health Research Center, Department of Nutrition, Lorestan University of Medical Sciences, Khorramabad, Iran

6 Department of Pathology, Lorestan University of Medical Sciences, Khorramabad, Iran


Objective(s): 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.


Main Subjects

1. Zhuo M. Neuronal mechanism for neuropathic pain. Mol Pain 2007;3:14.  

2. Dworkin RH, Backonja M, Rowbotham MC, Allen RR, Argoff CR, Bennett GJ, et al. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol 2003;60:1524-1534.

3. De Jongh RF, Vissers KC, Meert TF, Booij LH, De Deyne CS, Heylen RJ. The role of interleukin-6 in nociception and pain. Anesth Analg 2003;96:1096-1103.

4. Saika F, Kiguchi N, Kobayashi Y, Kishioka S. Peripheral alpha4beta2 nicotinic acetylcholine receptor signalling attenuates tactile allodynia and thermal hyperalgesia after nerve injury in mice. Acta Physiol (Oxf) 2015;213:462-471.  

5. Ma W, Quirion R. Does COX2-dependent PGE2 play a role in neuropathic pain? Neurosci Lett 2008;437:165-169.

6. Naik AK, Tandan SK, Dudhgaonkar SP, Jadhav SH, Kataria M, Prakash VR, et al. Role of oxidative stress in pathophysiology of peripheral neuropathy and modulation by N-acetyl-L-cysteine in rats. Eur J Pain 2006;10:573-579.

7. Kielian T, Esen N, Liu S, Phulwani NK, Syed MM, Phillips N, et al. Minocycline modulates neuroinflammation independently of its antimicrobial activity in staphylococcus aureus-induced brain abscess. Am J Pathol 2007;171:1199-1214.

8. Kraus RL, Pasieczny R, Lariosa-Willingham K, Turner MS, Jiang A, Trauger JW. Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical-scavenging activity.  J Neurochem 2005;94:819-827.

9. Tikka TM, Koistinaho JE. Minocycline provides neuroprotection against N-methyl-D-aspartate neurotoxicity by inhibiting microglia. J Immunol 2001;166:7527-7533.

10. Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci U S A 1999;96:13496-13500.

11. Mishra MK, Ghosh D, Duseja R, Basu A. Antioxidant potential of M