Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-23T12:29:25.944Z Has data issue: false hasContentIssue false
  • English
  • Français

Antinociceptive effect of N-acetyl glucosamine in a rat model of neuropathic pain

Published online by Cambridge University Press:  03 February 2022

Ehsan Mohebbi ,
Mehdi Molavi ,
Mohamadreza Amin ,
Bahareh Amin Open the ORCID record for Bahareh Amin [Opens in a new window]  and
Mohammad Sahebkar
Ehsan Mohebbi
Affiliation:
Student Research Committee, Sabzevar University of Medical Sciences, Sabzevar, Iran
Mehdi Molavi
Affiliation:
Department of Internal Medicine, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran
Mohamadreza Amin
Affiliation:
Laboratory Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
Bahareh Amin*
Affiliation:
Cellular and Molecular Research Center, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran
Mohammad Sahebkar
Affiliation:
School of Nursing, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada
*
Author for correspondence: Bahareh Amin, Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

This study was aimed at evaluating the efficacy of glucosamine and potential mechanisms of actions in a neuropathic pain model in rats.

Methods:

Glucosamine (500, 1000 and 2000 mg/kg) was administered via gavage route, 1 day before the chronic constriction injury (CCI) of sciatic nerve and daily for 14 days (prophylactic regimen), or from days 5 to 14 post-injury (therapeutic regimen), as the indicators of neuropathic pain, mechanical allodynia, cold allodynia and thermal hyperalgesia were assessed on days 0, 3, 5, 7, 10 and 14 after ligation. Inducible nitric oxide synthase (iNOS) and tumour necrosis factor alpha (TNF-α) gene expressions were measured by real-time polymerase chain reaction. TNF-α protein content was measured using the enzyme-linked immunosorbent assay method.

Results:

Three days after nerve injury, the threshold of pain was declined among animals subjected to neuropathic pain. Mechanical and cold allodynia, as well as thermal hyperalgesia were attenuated by glucosamine (500, 1000, 2000 mg/kg) in the prophylactic regimen. However, existing pain was not decreased by this drug. Increased mRNA expression of iNOS and TNF-α was significantly reduced in the spinal cord of CCI animals by glucosamine (500, 1000, 2000 mg/kg) in the prophylactic regimen. The overall expression of spinal TNF-α was increased by CCI, but this increase was reduced in animals receiving glucosamine prophylactic treatment.

Conclusion:

Findings suggest that glucosamine as a safe supplement may be a useful candidate in preventing neuropathic pain following nerve injury. Antioxidant and anti-inflammatory effects may be at least in part responsible for the antinociceptive effects of this drug.

Keywords

neuropathic painchronic constriction injuryglucosamineinflammatory markersoxidative stress
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 34 , Issue 5 , October 2022 , pp. 260 - 268
Check for updates
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Al-Mahmood, S, Abdullah, STBC, Nik Ahmad, NNF, Mohamed, AHB and Tariq, A (2016) Analgesic synergism of gabapentin and carbamazepine in rat model of diabetic neuropathic pain. Tropical Journal of Pharmaceutical Research 15(6), 1191–1195.CrossRefGoogle Scholar
Allen, BL and Rapraeger, AC (2003) Spatial and temporal expression of heparan sulfate in mouse development regulates FGF and FGF receptor assembly. Journal of Cellular Biology 163(3), 637–648.CrossRefGoogle ScholarPubMed
Amin, B, Heravi Taheri, MM and Hosseinzadeh, H (2014) Effects of intraperitoneal thymoquinone on chronic neuropathic pain in rats. Planta Medica 80, 1269–1277.Google ScholarPubMed
Baliki, M, Calvo, O, Chialvo, DR and Apkarian, AV (2005) Spared nerve injury rats exhibit thermal hyperalgesia on an automated operant dynamic thermal escape task. Molecular Pain 1, 18.CrossRefGoogle Scholar
Basiri, F, Rad, A, Mahdian, D, Molavi, M and Amin, B (2019) Effects of glucosamine against morphine-induced antinociceptive tolerance and dependence in mice. Journal of Biomedical Science 26(1), 21.CrossRefGoogle ScholarPubMed
Bennett, GJ, Chung, JM, Honore, M and Seltzer, Z (2003) Models of neuropathic pain in the rat. Current Protocols in Pharmacology Chapter 5, Unit5.32.Google ScholarPubMed
Bradford, MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analitical Biochemistry 72(1-2), 248–254.CrossRefGoogle ScholarPubMed
Carniglia, L, Ramirez, D, Durand, D, Saba, J, Turati, J, Caruso, C, Scimonelli, TN and Lasaga, M (2017) Neuropeptides and microglial activation in inflammation, pain, and neurodegenerative diseases. Mediators of Inflammation 5048616(6), 2017–23.Google Scholar
Chaparro, LE, Wiffen, PJ, Moore, RA and Gilron, I (2012) Combination pharmacotherapy for the treatment of neuropathic pain in adults. Cochrane Database Systematic Review 2012, Cd008943.Google Scholar
Charan, J and Kantharia, ND (2013) How to calculate sample size in animal studies? Journal of Pharmacology and Pharmacotherapy 4(4), 303–306.CrossRefGoogle ScholarPubMed
Chiu, HW, Li, LH, Hsieh, CY, Rao, YK, Chen, FH, Chen, A, Ka, SM and Hua, KF (2019) Glucosamine inhibits IL-1beta expression by preserving mitochondrial integrity and disrupting assembly of the NLRP3 inflammasome. Scientific Reports 9(1), 5603.CrossRefGoogle ScholarPubMed
Conti, A, Miscusi, M, Cardali, S, Germano, A, Suzuki, H, Cuzzocrea, S and Tomasello, F (2007) Nitric oxide in the injured spinal cord: synthases cross-talk, oxidative stress and inflammation. Brain Reseach Reviews 54(1), 205–218.CrossRefGoogle ScholarPubMed
Dostrovsky, NR, Towheed, TE, Hudson, RW and Anastassiades, TP (2011) The effect of glucosamine on glucose metabolism in humans: a systematic review of the literature. Osteoarthritis and Cartilage 19(4), 375–380.CrossRefGoogle ScholarPubMed
Dworkin, RH, O'connor, AB, Audette, J, Baron, R, Gourlay, GK, Haanpaa, ML, Kent, JL, Krane, EJ, Lebel, AA, Levy, RM, Mackey, SC, Mayer, J, Miaskowski, C, Raja, SN, Rice, AS, Schmader, KE, Stacey, B, Stanos, S, Treede, RD, Turk, DC, Walco, GA and Wells, CD (2010) Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clinic Proceedings 85(3), S3–14.CrossRefGoogle ScholarPubMed
Eddy, NB and Leimbach, D (1953) Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines. Journal of Pharmacology and Experimental Therapeutics 107, 385–393.Google ScholarPubMed
Gilzad-Kohan, MH and Jamali, F (2012) Glucosamine and adjuvant arthritis: a pharmacokinetic and pharmacodynamic study. European Journal of Pharmaceutical Science 47(2), 387–393.CrossRefGoogle ScholarPubMed
Gwak, YS, Hassler, SE and Hulsebosch, CE (2013) Reactive oxygen species contribute to neuropathic pain and locomotor dysfunction via activation of CamKII in remote segments following spinal cord contusion injury in rats. Pain 154(9), 1699–1708.CrossRefGoogle ScholarPubMed
Hua, J, Suguro, S, Hirano, S, Sakamoto, K and Nagaoka, I (2005) Preventive actions of a high dose of glucosamine on adjuvant arthritis in rats. Inflammatory Research 54(3), 127–132.CrossRefGoogle ScholarPubMed
Hwang, SY, Shin, JH, Hwang, JS, Kim, SY, Shin, JA, Oh, ES, Oh, S, Kim, JB, Lee, JK, Han, IO (2010) Glucosamine exerts a neuroprotective effect via suppression of inflammation in rat brain ischemia/reperfusion injury. Glia 58(15), 1881–1892.CrossRefGoogle Scholar
Jamialahmadi, K, Sadeghnia, HR, Mohammadi, G, Kazemabad, AM and Hosseini, M (2013) Glucosamine alleviates scopolamine induced spatial learning and memory deficits in rats. Pathophysiology 20(4), 263–267.CrossRefGoogle ScholarPubMed
Largo, R, Alvarez-Soria, MA, Diez-Ortego, I, Calvo, E, Sanchez-Pernaute, O, Egido, J and Herrero-Beaumont, G (2003) Glucosamine inhibits IL-1beta-induced NFkappaB activation in human osteoarthritic chondrocytes. Osteoarthritis Cartilage 11(4), 290–298.CrossRefGoogle ScholarPubMed
Lindner, ML, Bourin, C, Chen, P, McElroy, JF, Leet, JE, Hogan, JB, Stock, DA and Machet, F (2006) Adverse effects of gabapentin and lack of anti-allodynic efficacy of amitriptyline in the streptozotocin model of painful diabetic neuropathy. Experimental and Clinical Psychopharmacology 14(1), 42–51.CrossRefGoogle ScholarPubMed
Meymandi, MS, Sepehri, GH, Abdolsamadi, M, Shaabani, M, Heravi, G, Yazdanpanah, O and Aghtaei, M-M (2017) The effects of co-administration of pregabalin and vitamin E on neuropathic pain induced by partial sciatic nerve ligation in male rats. Inflammopharmacology 25(2), 237–246.CrossRefGoogle ScholarPubMed
Naik, AK, Tandan, SK, Dudhgaonkar, SP, Jadhav, SH, Kataria, M, Prakash, VR and Kumar, D (2006) Role of oxidative stress in pathophysiology of peripheral neuropathy and modulation by N-acetyl-L-cysteine in rats. European Journal of Pain 10(7), 573–579.CrossRefGoogle ScholarPubMed
Nielsen, CK, Lewis, RJ, Alewood, D, Drinkwater, R, Palant, E, Patterson, M, Yaksh, TL, McCumber, D and Smit, MT (2005) Anti-allodynic efficacy of the χ-conopeptide, Xen2174, in rats with neuropathic pain. Pain 118(1), 112–124.CrossRefGoogle ScholarPubMed
Ossipov, MH, Lai, J, Malan, TP Jr and Porreca, F (2000) Spinal and supraspinal mechanisms of neuropathic pain. Annals of New York Academy of Sciences 909, 12–24.CrossRefGoogle ScholarPubMed
Persiani, S, Roda, E, Rovati, LC, Locatelli, M, Giacovelli, G and Roda, A (2005) Glucosamine oral bioavailability and plasma pharmacokinetics after increasing doses of crystalline glucosamine sulfate in man. Osteoarthritis Cartilage 13(12), 1041–1049.CrossRefGoogle ScholarPubMed
Pertovaara, A, Wei, H, Kalmari, J and Ruotsalainen, M (2001) Pain behavior and response properties of spinal dorsal horn neurons following experimental diabetic neuropathy in the rat: modulation by nitecapone, a COMT inhibitor with antioxidant properties. Experimental Neurology 167(2), 425–434.CrossRefGoogle ScholarPubMed
Raghavendra, V, Tanga, F and Deleo, JA (2003) Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. Journal of Pharmacology and Experimental Therapeutics 306(2), 624–630.CrossRefGoogle ScholarPubMed
Rahbardar, MG, Amin, B, Mehri, S, Mirnajafi-Zadeh, SJ and Hosseinzadeh, H (2018) Rosmarinic acid attenuates development and existing pain in a rat model of neuropathic pain: an evidence of anti-oxidative and anti-inflammatory effects. Phytomedicine 40(7), 59–67.CrossRefGoogle Scholar
Rahimian, R, Lalancette-Hébert, M, ChengWeng, Y, Sato, S and Kriz, J (2020) Glucosamine-mediated immunomodulation after stroke is sexually dimorphic. Brain, Behavior, & Immunity - Health 3, 10041.CrossRefGoogle ScholarPubMed
Rajanandh, MG, Kosey, S and Prathiksha, G (2014) Assessment of antioxidant supplementation on the neuropathic pain score and quality of life in diabetic neuropathy patients – a randomized controlled study. Pharmacological Reports 66(1), 44–48.CrossRefGoogle ScholarPubMed
Sal'nikova, SI, Drogovoz, SM and Zupanets, IA (1990) The liver-protective properties of D-glucosamine. Farmakologiia i Toksikologiia 53, 33–35.Google ScholarPubMed
Schmittgen, TD and Livak, KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nature Protocols 3(6), 1101–1108.CrossRefGoogle ScholarPubMed
Setnikar, I, Cereda, R, Pacini, MA and Revel, L (1991) Antireactive properties of glucosamine sulfate. Arzneimittel-Forschung 41, 157–161.Google ScholarPubMed
Shin, JA, Hwang, JS, Kim, SY, Oh, SK, Nam, G and Han, IO (2013) A novel glucosamine derivative exerts anti-inflammatory actions via inhibition of nuclear factor-kappaB. Neuroscience Letters 550, 162–167.CrossRefGoogle ScholarPubMed
Staunton, CA, Barrett-Jolley, R, Djouhri, L and Thippeswamy, T (2018) Inducible nitric oxide synthase inhibition by 1400W limits pain hypersensitivity in a neuropathic pain rat model. Experimental Physiology 103(4), 535–544.CrossRefGoogle Scholar
Tsuji, T, Yoon, J, Kitano, N, Okura, T and Tanaka, K (2015) Effects of N-acetyl glucosamine and chondroitin sulfate supplementation on knee pain and self-reported knee function in middle-aged and older Japanese adults: a randomized, double-blind, placebo-controlled trial. Aging Clinical and Experimental Research 28(2), 197–205.CrossRefGoogle ScholarPubMed
Valsecchi, AE, Franchi, S, Panerai, AE, Sacerdote, P, Trovato, AE and Colleoni, M (2008) Genistein, a natural phytoestrogen from soy, relieves neuropathic pain following chronic constriction sciatic nerve injury in mice: anti-inflammatory and antioxidant activity. Journal of Neurochemistry 107(1), 230–240.CrossRefGoogle ScholarPubMed
Holbech, JV, Jung, A, Jonsson, T, Wanning, M, Bredahl, C and W.Bach, F (2017) Combination treatment of neuropathic pain: Danish expert recommendations based on a Delphi process. Journal of Pain Research 10, 1467–1475.CrossRefGoogle ScholarPubMed
Van Hecke, O, Austin, SK, Khan, RA, Smith, BH and Torrance, N (2014) Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain 155(4), 654–662.CrossRefGoogle ScholarPubMed
Wiffen, PJ, Derry, S, Bell, RF, Rice, AS, Tolle, TR, Phillips, T and Moore, RA (2017) Gabapentin for chronic neuropathic pain in adults. Cochrane Database Systematic Review 6(2), Cd007938.Google ScholarPubMed
Wodarski, R, Clark, AK, Grist, J, Marchand, F and Malcangio, M (2009) Gabapentin reverses microglial activation in the spinal cord of streptozotocin-induced diabetic rats. European Journal of Pain 13(8), 807–811.CrossRefGoogle ScholarPubMed
Yan, Y, Wanshun, L, Baoqin, H, Changhong, W, Chenwei, F, Bing, L and Liehuan, C (2007) The antioxidative and immunostimulating properties of d-glucosamine. International Immunopharmacology 7(1), 29–35.CrossRefGoogle ScholarPubMed
Zhang, GX, Yu, S, Gran, B and Rostami, A (2005) Glucosamine abrogates the acute phase of experimental autoimmune encephalomyelitis by induction of Th2 response. Journal of Immunology 175(11), 7202–7208.CrossRefGoogle ScholarPubMed
Zimmermann, M (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16(2), 109–110.CrossRefGoogle ScholarPubMed