Activation of Astrocytes and Microglia in the C3–T4 Dorsal Horn by Lower Trunk Avulsion in a Rat Model of Neuropathic Pain

Iwasaki, Ryutaro; Matsuura, Yusuke; Ohtori, Seiji; Suzuki, Takane; Kuniyoshi, Kazuki; Takahashi, Kazuhisa

doi:10.1016/j.jhsa.2013.01.034

Cited by 16 publications

(15 citation statements)

References 27 publications

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“…We see this change at both time points, but it is more pronounced two weeks after injury. These data are in accordance with our group and others who have shown localized increases in markers of astrocyte activation following SCI [23] , [24] , [55] , [56] . The observed increase in GFAP is seen only at the injury epicenter on the ipsilateral side, suggesting that this change is region-specific and may not play a role in potential above- or below-level changes, at least in our model.…”

Section: Discussionsupporting

confidence: 94%

Persistent At-Level Thermal Hyperalgesia and Tactile Allodynia Accompany Chronic Neuronal and Astrocyte Activation in Superficial Dorsal Horn following Mouse Cervical Contusion Spinal Cord Injury

et al. 2014

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In humans, sensory abnormalities, including neuropathic pain, often result from traumatic spinal cord injury (SCI). SCI can induce cellular changes in the CNS, termed central sensitization, that alter excitability of spinal cord neurons, including those in the dorsal horn involved in pain transmission. Persistently elevated levels of neuronal activity, glial activation, and glutamatergic transmission are thought to contribute to the hyperexcitability of these dorsal horn neurons, which can lead to maladaptive circuitry, aberrant pain processing and, ultimately, chronic neuropathic pain. Here we present a mouse model of SCI-induced neuropathic pain that exhibits a persistent pain phenotype accompanied by chronic neuronal hyperexcitability and glial activation in the spinal cord dorsal horn. We generated a unilateral cervical contusion injury at the C5 or C6 level of the adult mouse spinal cord. Following injury, an increase in the number of neurons expressing ΔFosB (a marker of chronic neuronal activation), persistent astrocyte activation and proliferation (as measured by GFAP and Ki67 expression), and a decrease in the expression of the astrocyte glutamate transporter GLT1 are observed in the ipsilateral superficial dorsal horn of cervical spinal cord. These changes have previously been associated with neuronal hyperexcitability and may contribute to altered pain transmission and chronic neuropathic pain. In our model, they are accompanied by robust at-level hyperaglesia in the ipsilateral forepaw and allodynia in both forepaws that are evident within two weeks following injury and persist for at least six weeks. Furthermore, the pain phenotype occurs in the absence of alterations in forelimb grip strength, suggesting that it represents sensory and not motor abnormalities. Given the importance of transgenic mouse technology, this clinically-relevant model provides a resource that can be used to study the molecular mechanisms contributing to neuropathic pain following SCI and to identify potential therapeutic targets for the treatment of chronic pathological pain.

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Section: Discussionsupporting

confidence: 94%

Persistent At-Level Thermal Hyperalgesia and Tactile Allodynia Accompany Chronic Neuronal and Astrocyte Activation in Superficial Dorsal Horn following Mouse Cervical Contusion Spinal Cord Injury

et al. 2014

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“…The mechanisms that trigger and sustain astrocyte proliferation and activation need further investigation. Literature results revealed that mechanical allodynia and sustained pain may have the distinct mechanisms, which is not clear [9].…”

Section: Iba1 (Microglia)mentioning

confidence: 96%

“…The activation of microglial and astrocytes in dorsal horns of spinal cord lasted 3 months following BPA [7]. Astrocyte and microglia were activated in the injured and uninjured dorsal horn of the spinal cord after brachial plexus injury [9]. Therefore, we could observe the activation of microglia and astrocytes to prove whether the neuropathic pain exists.…”

Section: Introductionmentioning

confidence: 95%

“…Next, spinal cord from C7 levels were resected and the specimens immersed in the same fixative solution overnight at 4 • C. After storage in 0.01 M phosphate-buffered saline (PBS) containing 20% sucrose for 20 h at 4 • C, the specimens were then treated for 90 min at room temperature in blocking solution consisting of 0.01 M PBS containing 0.3% Triton X-100 and 3% skim milk. The immunohistochemical procedure was performed as described previously [9]. For staining of dorsal horn, the sections were processed for GFAP immunohistochemistry using a rabbit antibody to GFAP (1:200; Abcam, USA) and for Iba1 immunohistochemistry using a rabbit antibody to Iba1(1: 250; Abcam, USA) diluted in blocking solution and incubated for 20 h at 4 • C. Sections were incubated with DAB Envision anti rabbit reagents (Dako, K5007, Denmark).…”

Section: Immunohistochemistry For Gfap(astrocyte) and Iba1 (Microgliamentioning

confidence: 99%

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A new rat model of neuropathic pain: Complete brachial plexus avulsion

Wang

Liu

Zhou

et al. 2015

Neuroscience Letters

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“…This explains how the C5 root can drive pain in the hand. In this regard, in rats, Paszcuk et al and Iwasaki et al observed activation of glial cells from C3‐T4 dorsal horn and associated dorsal roots ganglions following avulsion of C8‐T1 roots. Under normal conditions, glial cells are known for having a number of housekeeping functions in the central nervous system .…”

Section: Discussionmentioning

confidence: 98%

The C5 root dermatome enlarges and modulates hand pain in total brachial plexus palsy

Bertelli

Ghizoni

2013

Microsurgery

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Hand pain is a major complaint in 80% of the patients with complete brachial plexus palsy; and, in 80% of these patients, the C5 root is ruptured and the C6-T1 roots avulsed from the spinal cord. It has been suggested that pain in brachial plexus injuries may not arise from avulsed roots, but rather from ruptured roots. Traditionally the C5 root dermatome does not extend to the hand. We have hypothesized that in total lesions of the brachial plexus the C5 root dermatome expands, reaching the hand. In 20 patients with confirmed C5 root rupture and C6-T1 root avulsion, we investigated the distribution of C5 root paresthesia six to eight weeks after grafting. After cervical percussion in search of Tinel’s sign, maps related to reported paresthesia were drawn on the affected limb. We observed that paresthesia following C5 root percussion reached the hands and fingers, dermatomes linked to the C6 and C8 roots. Immediately after percussion, for a few seconds, 14 patients who complained of pain during examination reported the augmentation of numbness and pain resolution. After brachial plexus injury, the C5 root dermatome expands and modulates hand pain.

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Activation of Astrocytes and Microglia in the C3–T4 Dorsal Horn by Lower Trunk Avulsion in a Rat Model of Neuropathic Pain

Cited by 16 publications

References 27 publications

Persistent At-Level Thermal Hyperalgesia and Tactile Allodynia Accompany Chronic Neuronal and Astrocyte Activation in Superficial Dorsal Horn following Mouse Cervical Contusion Spinal Cord Injury

Persistent At-Level Thermal Hyperalgesia and Tactile Allodynia Accompany Chronic Neuronal and Astrocyte Activation in Superficial Dorsal Horn following Mouse Cervical Contusion Spinal Cord Injury

A new rat model of neuropathic pain: Complete brachial plexus avulsion

The C5 root dermatome enlarges and modulates hand pain in total brachial plexus palsy

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