Behavioral and Anatomical Characterization of the Bilateral Sciatic Nerve Chronic Constriction (bCCI) Injury: Correlation of Anatomic Changes and Responses to Cold Stimuli

Datta, Sukdeb; Chatterjee, Koel; Kline, R.; Wiley, Ronald G.

doi:10.1186/1744-8069-6-7

Cited by 34 publications

(32 citation statements)

References 76 publications

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“…This type of allodynia has been described in animal pain models (45)(46)(47) and also in patients after hand fracture (48,49). However, the underlying mechanism(s) of cold allodynia in our model remains unclear.…”

Section: Discussionmentioning

confidence: 51%

Orthopedic surgery modulates neuropeptides and BDNF expression at the spinal and hippocampal levels

Zhang

Barde

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Pain is a critical component hindering recovery and regaining of function after surgery, particularly in the elderly. Understanding the role of pain signaling after surgery may lead to novel interventions for common complications such as delirium and postoperative cognitive dysfunction. Using a model of tibial fracture with intramedullary pinning in male mice, associated with cognitive deficits, we characterized the effects on the primary somatosensory system. Here we show that tibial fracture with pinning triggers cold allodynia and up-regulates nerve injury and inflammatory markers in dorsal root ganglia (DRGs) and spinal cord up to 2 wk after intervention. At 72 h after surgery, there is an increase in activating transcription factor 3 (ATF3), the neuropeptides galanin and neuropeptide Y (NPY), brain-derived neurotrophic factor (BDNF), as well as neuroinflammatory markers including ionized calcium-binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), and the fractalkine receptor CX3CR1 in DRGs. Using an established model of complete transection of the sciatic nerve for comparison, we observed similar but more pronounced changes in these markers. However, protein levels of BDNF remained elevated for a longer period after fracture. In the hippocampus, BDNF protein levels were increased, yet there were no changes in Bdnf mRNA in the parent granule cell bodies. Further, c-Fos was down-regulated in the hippocampus, together with a reduction in neurogenesis in the subgranular zone. Taken together, our results suggest that attenuated BDNF release and signaling in the dentate gyrus may account for cognitive and mental deficits sometimes observed after surgery.postoperative pain | nerve injury | memory | delirium | neurogenesis

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Section: Discussionmentioning

confidence: 51%

Orthopedic surgery modulates neuropeptides and BDNF expression at the spinal and hippocampal levels

Zhang

Barde

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Bilateral sciatic nerve chronic constriction injury (bCCI) is commonly used as a model for studying human neuropathic pain, in which chromic gut sutures are used to ligate each sciatic nerve. This model is characterized by long-lasting cold allodynia and mechanical hypersensitivity (25,26); however, no information is available on how miRNA expression patterns in the nociceptive system are altered.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

Shen

et al. 2013

International Journal of Molecular Medicine

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Abstract. Chronic neuropathic pain is associated with global changes in gene expression in different areas of the nociceptive pathway. MicroRNAs (miRNAs) are small (~22 nt long) noncoding RNAs, which are able to regulate hundreds of different genes post-transcriptionally. The aim of this study was to determine the miRNA expression patterns in the different regions of the pain transmission pathway using a rat model of human neuropathic pain induced by bilateral sciatic nerve chronic constriction injury (bCCI). Using microarray analysis and quantitative reverse transcriptase-PCR, we observed a significant upregulation in miR-341 expression in the dorsal root ganglion (DRG), but not in the spinal dorsal horn (SDH), hippocampus or anterior cingulate cortex (ACC), in the rats with neuropathic pain compared to rats in the naïve and sham-operated groups. By contrast, the expression of miR-203, miR-181a-1 * and miR-541 * was significantly reduced in the SDH of rats with neuropathic pain. Our data indicate that miR-341 is upregulated in the DRG, whereas miR-203, miR-181a-1 * and miR-541 * are downregulated in the SDH under neuropathic pain conditions. Thus, the differential expression of miRNAs in the nervous system may play a role in the development of chronic pain. These observations may aid in the development of novel treatment methods for neuropathic pain, which may involve miRNA gene therapy in local regions. IntroductionNeuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting either the peripheral or central nervous system (1,2). Although pain has been investigated in depth for decades, neuropathic pain is still frequently under-treated (3), due to poor understanding of its pathophysiological and molecular mechanisms. Several regions of the nociceptive pathway, including the anterior cingulate cortex (ACC), hippocampus, spinal dorsal horn (SDH) and dorsal root ganglion (DRG), are involved in the development and maintenance of neuropathic pain (4-9). Several recent studies have shown that peripheral and central sensitization are associated with global changes in gene expression in different regions of the pain transmission pathway, and that these changes may be part of the mechanisms behind neuropathic pain (10-13). In order to elucidate the molecular mechanisms underlying neuropathic pain, it is essential to determine how gene expression patterns are altered by nerve injuries and how these alterations lead to the development and maintenance of chronic pain.miRNAs are a large class of short non-coding RNAs (~22 nt long), many of which are expressed either predominantly or exclusively in the nervous system (14-21). Furthermore, changes (either increases or decreases) in miRNA expression have been found in many disease states (22-24). Bilateral sciatic nerve chronic constriction injury (bCCI) is commonly used as a model for studying human neuropathic pain, in which chromic gut sutures are used to ligate each sciatic nerve. This model is characterized by long-lasting cold all...

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“…As heat allodynia is a clinically rare condition, cold stimulus is preferred as the thermal stimulus for neuropathic pain models (32)(33)(34). Acetone induces a pain-free cold sensation by evaporation of liquid from the normal scalp.…”

Section: Discussionmentioning

confidence: 99%

Nitroglycerin challenge induces lateralized headache in nasociliarynerve-ligated rats: implications for chronic migraine

et al. 2017

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Background/aim: Chronic migraine is a common debilitating disease with limited treatment options. We aimed to develop a novel model for chronic migraine by ligating the nasociliary nerve (NCL) and administering nitroglycerin (NTG) to exacerbate acute headache attacks. Materials and methods: Exacerbation of the headache was induced by NTG (10 mg/kg, subcutaneously) administered to male Wistar rats (n = 36) 14 days following unilateral NCL. Cutaneous and cold allodynia was tested using Von Frey (VF) filaments and acetone, respectively. Elevated plus maze (EPM) results and c-fos immunoreactivity of TNC were investigated. Results: NTG administration significantly decreased VF threshold values only in the nasociliary nerve (NCN) territory and the ipsilateral forepaw (P = 0.0001, P = 0.02). Cold allodynia developed in bilateral NCN territories (P = 0.013). The number/rate of entrance to open arms in the EPM was significantly decreased in NCN-ligated rats (P = 0.042, P = 0.035). Immunohistochemistry disclosed significantly increased c-fos-positive neurons in ipsilateral brainstem TNC compared to the contralateral side (brain stem LI ipsilateral 25.4 ± 4.7, contralateral 11.8 ± 1.9, P < 0.05) in chronic NCN-ligated rats exposed to acute NTG. Conclusion:The presented model provides a valid chronic migraine model relevant to humans, as NTG challenge in chronic NCL rats generated lateralized headache with cephalic and extracephalic allodynia, altered cold sensitivity, anxiety, and neuronal activation in the nociceptive laminae of brainstem trigeminal pain nuclei.

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Behavioral and Anatomical Characterization of the Bilateral Sciatic Nerve Chronic Constriction (bCCI) Injury: Correlation of Anatomic Changes and Responses to Cold Stimuli

Cited by 34 publications

References 76 publications

Orthopedic surgery modulates neuropeptides and BDNF expression at the spinal and hippocampal levels

Orthopedic surgery modulates neuropeptides and BDNF expression at the spinal and hippocampal levels

Differential expression of miRNAs in the nervous system of a rat model of bilateral sciatic nerve chronic constriction injury

Nitroglycerin challenge induces lateralized headache in nasociliarynerve-ligated rats: implications for chronic migraine

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