Skip to main content
Top
Published in: BMC Anesthesiology 1/2014

Open Access 01-12-2014 | Research article

Intrathecal injection of fluorocitric acid inhibits the activation of glial cells causing reduced mirror pain in rats

Authors: Jing Cao, Zhihua Li, Zhenhua Zhang, Xiuhua Ren, Qingzan Zhao, Jinping Shao, Ming Li, Jiannan Wang, Puchao Huang, Weidong Zang

Published in: BMC Anesthesiology | Issue 1/2014

Login to get access

Abstract

Background

Growing evidence has shown that unilateral nerve injury results in pain hypersensitivity in the ipsilateral and contralateral sides respective to the injury site. This phenomenon is known as mirror image pain (MIP). Glial cells have been indicated in the mechanism of MIP; however, it is not clear how glial cells are involved in MIP.

Methods

To observe phenomenon MIP and the following mechanism, 20 adult male Sprague–Dawley rats (weighing 180–220 g) were separated into two groups: Sham Group (n = 10) and left L5 spinal nerve ligated and sectioned (SNL) group (n = 10). Thermal hyperalgesia and mechanical hypersensitivity were measured for both groups to determine if the SNL model had Mirror image of Pain (MIP). Nav1.7 protein expression in DRG was analyzed using immunohistochemistry and western-blotting. And then to observe the effect of fluorocitrate on MIP, 15 rats were separated into three Groups: Sham Group (n = 5); SNL + FC group: intrathecal injection of Fluorocitric acid(FC) 1 nmol/10 μL (n = 5); SNL + NS group: intrathecal injection of 0.9% Normal Saline (n = 5). Behavior testing, immunocytochemistry, and western-blotting using dorsal root ganglion (DRG) from both sides were then conducted.

Results

The results showed pain hypersensitivity in both hind-paws of the SNL animals, Mechanical tests showed the paw withdrawal threshold dropped from 13.30 ± 1.204 g to 2.57 ± 1.963 g at 14 d as will as the ipsilateral paw thermal withdrawal threshold dropped from 16.5 ± 2.236 s to 4.38 ± 2.544 s at 14d. Mechanical tests showed the contralateral paw withdrawal threshold dropped from 14.01 ± 1.412 to 4.2 ± 1.789 g at 7d will the thermal withdrawal threshold dropped from 16.8 ± 2.176 s to 7.6 ± 1.517 s at 7d. Nav1.7 expression increased and glial cells actived in bilateral side DRG after SNL compared with sham group. After intrathecal injection of fluorocitrate, the glial cell in bilatral DRG were inhibited and the pain behavior were reversed in both hindpaws too.

Conclusions

Fluorocitrate can inhibit the activation of glial cells in spinal cord and DRG, and reduce MIP.
Appendix
Available only for authorised users
Literature
1.
go back to reference Dubovy P, Brazda V, Klusakova I, Hradilova-Svizenska I: Bilateral elevation of interleukin-6 protein and mRNA in both lumbar and cervical dorsal root ganglia following unilateral chronic compression injury of the sciatic nerve. J Neuroinflammation. 2013, 10: 55-10.1186/1742-2094-10-55.CrossRefPubMedPubMedCentral Dubovy P, Brazda V, Klusakova I, Hradilova-Svizenska I: Bilateral elevation of interleukin-6 protein and mRNA in both lumbar and cervical dorsal root ganglia following unilateral chronic compression injury of the sciatic nerve. J Neuroinflammation. 2013, 10: 55-10.1186/1742-2094-10-55.CrossRefPubMedPubMedCentral
2.
go back to reference Svizenska IH, Brazda V, Klusakova I, Dubovy P: Bilateral changes of cannabinoid receptor type 2 protein and mRNA in the dorsal root Ganglia of a rat neuropathic pain model. J Histochem Cytochem. 2013, 61 (7): 529-547. 10.1369/0022155413491269.CrossRefPubMedPubMedCentral Svizenska IH, Brazda V, Klusakova I, Dubovy P: Bilateral changes of cannabinoid receptor type 2 protein and mRNA in the dorsal root Ganglia of a rat neuropathic pain model. J Histochem Cytochem. 2013, 61 (7): 529-547. 10.1369/0022155413491269.CrossRefPubMedPubMedCentral
3.
go back to reference Seidel S, Kasprian G, Furtner J, Schopf V, Essmeister M, Sycha T, Auff E, Prayer D: Mirror therapy in lower limb amputees–a look beyond primary motor cortex reorganization. RoFo. 2011, 183 (11): 1051-1057. 10.1055/s-0031-1281768.CrossRefPubMed Seidel S, Kasprian G, Furtner J, Schopf V, Essmeister M, Sycha T, Auff E, Prayer D: Mirror therapy in lower limb amputees–a look beyond primary motor cortex reorganization. RoFo. 2011, 183 (11): 1051-1057. 10.1055/s-0031-1281768.CrossRefPubMed
4.
go back to reference Behera D, Behera S, Jacobs KE, Biswal S: Bilateral peripheral neural activity observed in vivo following unilateral nerve injury. Am J Nucl Med Mol Imaging. 2013, 3 (3): 282-290.PubMedPubMedCentral Behera D, Behera S, Jacobs KE, Biswal S: Bilateral peripheral neural activity observed in vivo following unilateral nerve injury. Am J Nucl Med Mol Imaging. 2013, 3 (3): 282-290.PubMedPubMedCentral
5.
go back to reference Dubovy P, Klusakova I, Svizenska I, Brazda V: Satellite glial cells express IL-6 and corresponding signal-transducing receptors in the dorsal root ganglia of rat neuropathic pain model. Neuron Glia Biol. 2010, 6 (1): 73-83. 10.1017/S1740925X10000074.CrossRefPubMed Dubovy P, Klusakova I, Svizenska I, Brazda V: Satellite glial cells express IL-6 and corresponding signal-transducing receptors in the dorsal root ganglia of rat neuropathic pain model. Neuron Glia Biol. 2010, 6 (1): 73-83. 10.1017/S1740925X10000074.CrossRefPubMed
6.
go back to reference Cox JJ, Sheynin J, Shorer Z, Reimann F, Nicholas AK, Zubovic L, Baralle M, Wraige E, Manor E, Levy J, Woods CG, Parvari R: Congenital insensitivity to pain: novel SCN9A missense and in-frame deletion mutations. Hum Mutat. 2010, 31 (9): E1670-E1686. 10.1002/humu.21325.CrossRefPubMed Cox JJ, Sheynin J, Shorer Z, Reimann F, Nicholas AK, Zubovic L, Baralle M, Wraige E, Manor E, Levy J, Woods CG, Parvari R: Congenital insensitivity to pain: novel SCN9A missense and in-frame deletion mutations. Hum Mutat. 2010, 31 (9): E1670-E1686. 10.1002/humu.21325.CrossRefPubMed
7.
go back to reference Han C, Rush AM, Dib-Hajj SD, Li S, Xu Z, Wang Y, Tyrrell L, Wang X, Yang Y, Waxman SG: Sporadic onset of erythermalgia: a gain-of-function mutation in Nav1.7. Ann Neurol. 2006, 59 (3): 553-558. 10.1002/ana.20776.CrossRefPubMed Han C, Rush AM, Dib-Hajj SD, Li S, Xu Z, Wang Y, Tyrrell L, Wang X, Yang Y, Waxman SG: Sporadic onset of erythermalgia: a gain-of-function mutation in Nav1.7. Ann Neurol. 2006, 59 (3): 553-558. 10.1002/ana.20776.CrossRefPubMed
8.
go back to reference Souza GR, Talbot J, Lotufo CM, Cunha FQ, Cunha TM, Ferreira SH: Fractalkine mediates inflammatory pain through activation of satellite glial cells. Proc Natl Acad Sci U S A. 2013, 110 (27): 11193-11198. 10.1073/pnas.1307445110.CrossRefPubMedPubMedCentral Souza GR, Talbot J, Lotufo CM, Cunha FQ, Cunha TM, Ferreira SH: Fractalkine mediates inflammatory pain through activation of satellite glial cells. Proc Natl Acad Sci U S A. 2013, 110 (27): 11193-11198. 10.1073/pnas.1307445110.CrossRefPubMedPubMedCentral
9.
go back to reference Wei DM, Liu FY: The mechanism of the glial cells involved in neuropathic pain. Sheng li ke xue jin zhan [Progress in physiology]. 2012, 43 (6): 427-432. Wei DM, Liu FY: The mechanism of the glial cells involved in neuropathic pain. Sheng li ke xue jin zhan [Progress in physiology]. 2012, 43 (6): 427-432.
10.
go back to reference Takeda M, Takahashi M, Matsumoto S: Contribution of the activation of satellite glia in sensory ganglia to pathological pain. Neurosci Biobehav Rev. 2009, 33 (6): 784-792. 10.1016/j.neubiorev.2008.12.005.CrossRefPubMed Takeda M, Takahashi M, Matsumoto S: Contribution of the activation of satellite glia in sensory ganglia to pathological pain. Neurosci Biobehav Rev. 2009, 33 (6): 784-792. 10.1016/j.neubiorev.2008.12.005.CrossRefPubMed
11.
go back to reference Jasmin L, Vit JP, Bhargava A, Ohara PT: Can satellite glial cells be therapeutic targets for pain control?. Neuron Glia Biol. 2010, 6 (1): 63-71. 10.1017/S1740925X10000098.CrossRefPubMedPubMedCentral Jasmin L, Vit JP, Bhargava A, Ohara PT: Can satellite glial cells be therapeutic targets for pain control?. Neuron Glia Biol. 2010, 6 (1): 63-71. 10.1017/S1740925X10000098.CrossRefPubMedPubMedCentral
12.
go back to reference Stephenson W: Deficiencies in the National Institute of Health’s guidelines for the care and protection of laboratory animals. The Journal of medicine and philosophy. 1993, 18 (4): 375-388. 10.1093/jmp/18.4.375.CrossRefPubMed Stephenson W: Deficiencies in the National Institute of Health’s guidelines for the care and protection of laboratory animals. The Journal of medicine and philosophy. 1993, 18 (4): 375-388. 10.1093/jmp/18.4.375.CrossRefPubMed
13.
go back to reference Kawasaki Y, Zhang L, Cheng JK, Ji RR: Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci Off J Soc Neurosci. 2008, 28 (20): 5189-5194. 10.1523/JNEUROSCI.3338-07.2008.CrossRef Kawasaki Y, Zhang L, Cheng JK, Ji RR: Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci Off J Soc Neurosci. 2008, 28 (20): 5189-5194. 10.1523/JNEUROSCI.3338-07.2008.CrossRef
14.
go back to reference Werner MU, Ringsted TK, Kehlet H, Wildgaard K: Sensory testing in patients with postthoracotomy pain syndrome: part 1: mirror-image sensory dysfunction. The Clinical journal of pain. 2013, 29 (9): 775-783. 10.1097/AJP.0b013e318277b646.CrossRefPubMed Werner MU, Ringsted TK, Kehlet H, Wildgaard K: Sensory testing in patients with postthoracotomy pain syndrome: part 1: mirror-image sensory dysfunction. The Clinical journal of pain. 2013, 29 (9): 775-783. 10.1097/AJP.0b013e318277b646.CrossRefPubMed
15.
go back to reference Takeda M, Takahashi M, Nasu M, Matsumoto S: Peripheral inflammation suppresses inward rectifying potassium currents of satellite glial cells in the trigeminal ganglia. Pain. 2011, 152 (9): 2147-2156. 10.1016/j.pain.2011.05.023.CrossRefPubMed Takeda M, Takahashi M, Nasu M, Matsumoto S: Peripheral inflammation suppresses inward rectifying potassium currents of satellite glial cells in the trigeminal ganglia. Pain. 2011, 152 (9): 2147-2156. 10.1016/j.pain.2011.05.023.CrossRefPubMed
16.
go back to reference Gong K, Yue Y, Zou X, Li D, Lin Q: Minocycline inhibits the enhancement of antidromic primary afferent stimulation-evoked vasodilation following intradermal capsaicin injection. Neurosci Lett. 2010, 482 (2): 177-181. 10.1016/j.neulet.2010.07.031.CrossRefPubMedPubMedCentral Gong K, Yue Y, Zou X, Li D, Lin Q: Minocycline inhibits the enhancement of antidromic primary afferent stimulation-evoked vasodilation following intradermal capsaicin injection. Neurosci Lett. 2010, 482 (2): 177-181. 10.1016/j.neulet.2010.07.031.CrossRefPubMedPubMedCentral
17.
go back to reference Brazda V, Klusakova I, Hradilova Svi Enska I, Dubovy P: Dynamic response to peripheral nerve injury detected by in situ hybridization of IL-6 and its receptor mRNAs in the dorsal root ganglia is not strictly correlated with signs of neuropathic pain. Molecular pain. 2013, 9 (1): 42-10.1186/1744-8069-9-42.CrossRefPubMedPubMedCentral Brazda V, Klusakova I, Hradilova Svi Enska I, Dubovy P: Dynamic response to peripheral nerve injury detected by in situ hybridization of IL-6 and its receptor mRNAs in the dorsal root ganglia is not strictly correlated with signs of neuropathic pain. Molecular pain. 2013, 9 (1): 42-10.1186/1744-8069-9-42.CrossRefPubMedPubMedCentral
18.
go back to reference Kung LH, Gong K, Adedoyin M, Ng J, Bhargava A, Ohara PT, Jasmin L: Evidence for glutamate as a neuroglial transmitter within sensory ganglia. PLoS One. 2013, 8 (7): e68312-10.1371/journal.pone.0068312.CrossRefPubMedPubMedCentral Kung LH, Gong K, Adedoyin M, Ng J, Bhargava A, Ohara PT, Jasmin L: Evidence for glutamate as a neuroglial transmitter within sensory ganglia. PLoS One. 2013, 8 (7): e68312-10.1371/journal.pone.0068312.CrossRefPubMedPubMedCentral
19.
go back to reference Ohara PT, Vit JP, Bhargava A, Jasmin L: Evidence for a role of connexin 43 in trigeminal pain using RNA interference in vivo. J Neurophysiol. 2008, 100 (6): 3064-3073. 10.1152/jn.90722.2008.CrossRefPubMedPubMedCentral Ohara PT, Vit JP, Bhargava A, Jasmin L: Evidence for a role of connexin 43 in trigeminal pain using RNA interference in vivo. J Neurophysiol. 2008, 100 (6): 3064-3073. 10.1152/jn.90722.2008.CrossRefPubMedPubMedCentral
20.
go back to reference Duan G, Xiang G, Zhang X, Yuan R, Zhan H, Qi D: A single-nucleotide polymorphism in SCN9A may decrease postoperative pain sensitivity in the general population. Anesthesiology. 2013, 118 (2): 436-442. 10.1097/ALN.0b013e31827dde74.CrossRefPubMed Duan G, Xiang G, Zhang X, Yuan R, Zhan H, Qi D: A single-nucleotide polymorphism in SCN9A may decrease postoperative pain sensitivity in the general population. Anesthesiology. 2013, 118 (2): 436-442. 10.1097/ALN.0b013e31827dde74.CrossRefPubMed
21.
go back to reference Wu MT, Huang PY, Yen CT, Chen CC, Lee MJ: A novel SCN9A mutation responsible for primary erythromelalgia and is resistant to the treatment of sodium channel blockers. PLoS One. 2013, 8 (1): e55212-10.1371/journal.pone.0055212.CrossRefPubMedPubMedCentral Wu MT, Huang PY, Yen CT, Chen CC, Lee MJ: A novel SCN9A mutation responsible for primary erythromelalgia and is resistant to the treatment of sodium channel blockers. PLoS One. 2013, 8 (1): e55212-10.1371/journal.pone.0055212.CrossRefPubMedPubMedCentral
Metadata
Title
Intrathecal injection of fluorocitric acid inhibits the activation of glial cells causing reduced mirror pain in rats
Authors
Jing Cao
Zhihua Li
Zhenhua Zhang
Xiuhua Ren
Qingzan Zhao
Jinping Shao
Ming Li
Jiannan Wang
Puchao Huang
Weidong Zang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2014
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/1471-2253-14-119

Other articles of this Issue 1/2014

BMC Anesthesiology 1/2014 Go to the issue