Download PDF
J Reconstr Microsurg 2018; 34(04): 264-269
DOI: 10.1055/s-0037-1621723
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Stable Rat Model of Mechanical Allodynia in Diabetic Peripheral Neuropathy: The Role of Nerve Compression

Chenlong Liao
1   Department of Neurosurgery, XinHua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, Republic of China
,
Min Yang
1   Department of Neurosurgery, XinHua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, Republic of China
,
Pengfei Liu
1   Department of Neurosurgery, XinHua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, Republic of China
,
Wenxiang Zhong
1   Department of Neurosurgery, XinHua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, Republic of China
,
Wenchuan Zhang
1   Department of Neurosurgery, XinHua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, Republic of China
› Author Affiliations
Further Information

Publication History

22 July 2017

18 November 2017

Publication Date:
02 February 2018 (online)

    Permissions and Reprints

Abstract

Background Preclinical studies involving animal models are essential for understanding the underlying mechanisms of diabetic neuropathic pain.

Methods Rats were divided into four groups: two controls and two experimental. Diabetes mellitus was induced by streptozotocin (STZ) injection in two experimental groups. The first group involved one sham operation. The second group involved one latex tube encircling the sciatic nerve. The vehicle-injection rats were used as two corresponding control groups: sham operation and encircled nerves. By the third week, STZ-injected rats with encircled nerves were further divided into three subgroups: one involving continuing observation and the other two involving decompression (removal of the latex tube) at different time points (third week and fifth week). Weight and blood glucose were monitored, and behavioral analysis, including paw withdrawal threshold (PWT) and latency, was performed every week during the experimental period (7 weeks).

Results Hyperglycemia was induced in all STZ-injected rats. A significant increase in weight was observed in the control groups when compared with the experimental groups. By the third week, more STZ-injected rats with encircled nerves developed mechanical allodynia than those without (P < 0.05), while no significant difference was noted (P > 0.05) on the incidence of thermal hyperalgesia. Mechanical allodynia, but not thermal hyperalgesia, could be ameliorated by the removal of the latex tube at an early stage (third week).

Conclusion With the combined use of a latex tube and STZ injection, a stable rat model of painful diabetic peripheral neuropathy (DPN) manifesting both thermal hyperalgesia and mechanical allodynia has been established.

Keywords

diabetic peripheral neuropathy - mechanical allodynia - animal model
 

  • References

  • 1 Quattrini C, Tesfaye S. Understanding the impact of painful diabetic neuropathy. Diabetes Metab Res Rev 2003; 19 (Suppl. 01) S2-S8
    CrossrefPubMedGoogle Scholar
  • 2 Zelman DC, Brandenburg NA, Gore M. Sleep impairment in patients with painful diabetic peripheral neuropathy. Clin J Pain 2006; 22 (08) 681-685
    CrossrefPubMedGoogle Scholar
  • 3 Gore M, Brandenburg NA, Dukes E, Hoffman DL, Tai KS, Stacey B. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. J Pain Symptom Manage 2005; 30 (04) 374-385
    CrossrefPubMedGoogle Scholar
  • 4 Coppey LJ, Davidson EP, Dunlap JA, Lund DD, Yorek MA. Slowing of motor nerve conduction velocity in streptozotocin-induced diabetic rats is preceded by impaired vasodilation in arterioles that overlie the sciatic nerve. Int J Exp Diabetes Res 2000; 1 (02) 131-143
    CrossrefPubMedGoogle Scholar
  • 5 Obrosova IG. Diabetic painful and insensate neuropathy: pathogenesis and potential treatments. Neurotherapeutics 2009; 6 (04) 638-647
    CrossrefPubMedGoogle Scholar
  • 6 Morrow TJ. Animal models of painful diabetic neuropathy: the STZ rat model. Curr Protoc Neurosci 2004; (09) 18 [Chapter 9]
    PubMedGoogle Scholar
  • 7 Chen SR, Samoriski G, Pan HL. Antinociceptive effects of chronic administration of uncompetitive NMDA receptor antagonists in a rat model of diabetic neuropathic pain. Neuropharmacology 2009; 57 (02) 121-126
    CrossrefPubMedGoogle Scholar
  • 8 Mixcoatl-Zecuatl T, Jolivalt CG. A spinal mechanism of action for duloxetine in a rat model of painful diabetic neuropathy. Br J Pharmacol 2011; 164 (01) 159-169
    CrossrefPubMedGoogle Scholar
  • 9 Fuchs D, Birklein F, Reeh PW, Sauer SK. Sensitized peripheral nociception in experimental diabetes of the rat. Pain 2010; 151 (02) 496-505
    CrossrefPubMedGoogle Scholar
  • 10 Manni L, Florenzano F, Aloe L. Electroacupuncture counteracts the development of thermal hyperalgesia and the alteration of nerve growth factor and sensory neuromodulators induced by streptozotocin in adult rats. Diabetologia 2011; 54 (07) 1900-1908
    CrossrefPubMedGoogle Scholar
  • 11 Upton AR, McComas AJ. The double crush in nerve entrapment syndromes. Lancet 1973; 2 (7825): 359-362
    PubMedGoogle Scholar
  • 12 Dellon AL, Mackinnon SE, Seiler IV WA. Susceptibility of the diabetic nerve to chronic compression. Ann Plast Surg 1988; 20 (02) 117-119
    CrossrefPubMedGoogle Scholar
  • 13 Obrosova IG, Xu W, Lyzogubov VV. , et al. PARP inhibition or gene deficiency counteracts intraepidermal nerve fiber loss and neuropathic pain in advanced diabetic neuropathy. Free Radic Biol Med 2008; 44 (06) 972-981
    CrossrefPubMedGoogle Scholar
  • 14 Li F, Drel VR, Szabó C, Stevens MJ, Obrosova IG. Low-dose poly(ADP-ribose) polymerase inhibitor-containing combination therapies reverse early peripheral diabetic neuropathy. Diabetes 2005; 54 (05) 1514-1522
    CrossrefPubMedGoogle Scholar
  • 15 Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 1994; 53 (01) 55-63
    CrossrefPubMedGoogle Scholar
  • 16 Dixon WJ. Efficient analysis of experimental observations. Annu Rev Pharmacol Toxicol 1980; 20: 441-462
    CrossrefPubMedGoogle Scholar
  • 17 Chen SR, Pan HL. Spinal endogenous acetylcholine contributes to the analgesic effect of systemic morphine in rats. Anesthesiology 2001; 95 (02) 525-530
    CrossrefPubMedGoogle Scholar
  • 18 Kim SH, Kwon JK, Kwon YB. Pain modality and spinal glia expression by streptozotocin induced diabetic peripheral neuropathy in rats. Lab Anim Res 2012; 28 (02) 131-136
    CrossrefPubMedGoogle Scholar
  • 19 Cheng KI, Wang HC, Chuang YT. , et al. Persistent mechanical allodynia positively correlates with an increase in activated microglia and increased P-p38 mitogen-activated protein kinase activation in streptozotocin-induced diabetic rats. Eur J Pain 2014; 18 (02) 162-173
    CrossrefPubMedGoogle Scholar
  • 20 Gajdosík A, Gajdosíková A, Stefek M, Navarová J, Hozová R. Streptozotocin-induced experimental diabetes in male Wistar rats. Gen Physiol Biophys 1999; 18 (Spec No): 54-62
    PubMedGoogle Scholar
  • 21 Baldea BI, Toader S, Orbai P. , et al. The influence of diabetes mellitus on survival of abdominal perforator flaps: an experimental study in rats with slowly induced diabetes mellitus. J Reconstr Microsurg 2015; 31 (02) 145-153
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Liao C, Yang M, Zhong W, Liu P, Zhang W. Association of myelinated primary afferents impairment with mechanical allodynia in diabetic peripheral neuropathy: an experimental study in rats. Oncotarget 2017; 8 (38) 64157-64169
    CrossrefPubMedGoogle Scholar
  • 23 Lee D, Dauphinée DM. Morphological and functional changes in the diabetic peripheral nerve: using diagnostic ultrasound and neurosensory testing to select candidates for nerve decompression. J Am Podiatr Med Assoc 2005; 95 (05) 433-437
    CrossrefPubMedGoogle Scholar
  • 24 Dellon AL. Susceptibility of nerve in diabetes to compression: implications for pain treatment. Plast Reconstr Surg 2014; 134 (04) (Suppl. 02) 142S-150S
    CrossrefPubMedGoogle Scholar
  • 25 Calcutt NA, Freshwater JD, Mizisin AP. Prevention of sensory disorders in diabetic Sprague-Dawley rats by aldose reductase inhibition or treatment with ciliary neurotrophic factor. Diabetologia 2004; 47 (04) 718-724
    CrossrefPubMedGoogle Scholar
  • 26 Pertovaara A, Wei H, Kalmari J, Ruotsalainen M. 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. Exp Neurol 2001; 167 (02) 425-434
    CrossrefPubMedGoogle Scholar
  • 27 Christianson JA, Ryals JM, Johnson MS, Dobrowsky RT, Wright DE. Neurotrophic modulation of myelinated cutaneous innervation and mechanical sensory loss in diabetic mice. Neuroscience 2007; 145 (01) 303-313
    CrossrefPubMedGoogle Scholar
  • 28 Drel VR, Pacher P, Vareniuk I. , et al. Evaluation of the peroxynitrite decomposition catalyst Fe(III) tetra-mesitylporphyrin octasulfonate on peripheral neuropathy in a mouse model of type 1 diabetes. Int J Mol Med 2007; 20 (06) 783-792
    PubMedGoogle Scholar
  • 29 Vareniuk I, Pavlov IA, Obrosova IG. Inducible nitric oxide synthase gene deficiency counteracts multiple manifestations of peripheral neuropathy in a streptozotocin-induced mouse model of diabetes. Diabetologia 2008; 51 (11) 2126-2133
    CrossrefPubMedGoogle Scholar
  • 30 Battista AF, Alban E. Effect of graded ligature compression on nerve conduction. Exp Neurol 1983; 80 (01) 186-194
    CrossrefPubMedGoogle Scholar
  • 31 Yagihashi S, Kamijo M, Watanabe K. Reduced myelinated fiber size correlates with loss of axonal neurofilaments in peripheral nerve of chronically streptozotocin diabetic rats. Am J Pathol 1990; 136 (06) 1365-1373
    PubMedGoogle Scholar
  • 32 Jaffey PB, Gelman BB. Increased vulnerability to demyelination in streptozotocin diabetic rats. J Comp Neurol 1996; 373 (01) 55-61
    CrossrefPubMedGoogle Scholar
  • 33 Lennertz RC, Medler KA, Bain JL, Wright DE, Stucky CL. Impaired sensory nerve function and axon morphology in mice with diabetic neuropathy. J Neurophysiol 2011; 106 (02) 905-914
    CrossrefPubMedGoogle Scholar
  • 34 Jiang BC, Sun WX, He LN, Cao DL, Zhang ZJ, Gao YJ. Identification of lncRNA expression profile in the spinal cord of mice following spinal nerve ligation-induced neuropathic pain. Mol Pain 2015; 11: 43
    PubMedGoogle Scholar
  • 35 Ma W, Eisenach JC. Chronic constriction injury of sciatic nerve induces the up-regulation of descending inhibitory noradrenergic innervation to the lumbar dorsal horn of mice. Brain Res 2003; 970 (1-2): 110-118
    CrossrefPubMedGoogle Scholar
  • 36 Richner M, Bjerrum OJ, Nykjaer A, Vaegter CB. The spared nerve injury (SNI) model of induced mechanical allodynia in mice. J Vis Exp 2011; (54) 3092
    PubMedGoogle Scholar
  • 37 Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell 2009; 139 (02) 267-284
    CrossrefPubMedGoogle Scholar