Chemical and mechanical nerve root insults induce differential behavioral sensitivity and glial activation that are enhanced in combination

Rothman, Sarah M.; Winkelstein, Beth A.

doi:10.1016/j.brainres.2007.08.064

Cited by 53 publications

(108 citation statements)

References 72 publications

(132 reference statements)

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“…GFAP is a major constituent of astrocyte intermediate filaments and is widely used as a sensitive marker of the reactive gliosis that occurs after CNS injury. Increases in GFAP reactivity at post-injury day 7 imply that astrocytic proliferation, if present at all, would have been evident before or at day 7 25) . Activation of local astrocytes and microglia in the spinal cord may contribute to rat pain-related behaviors, as both cells express receptors for several neurotransmitters, possibly including glutamate, substance P and other factors.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Minocycline on Motor Neuron Recovery and Neuropathic Pain in a Rat Model of Spinal Cord Injury

Cho

Cheong

Yang

et al. 2011

J Korean Neurosurg Soc

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Objective : Minocycline, a second-generation tetracycline-class antibiotic, has been well established to exert a neuroprotective effect in animal models and neurodegenerative disease through the inhibition of microglia. Here, we investigated the effects of minocycline on motor recovery and neuropathic pain in a rat model of spinal cord injury. Methods : To simulate spinal cord injury, the rats' spinal cords were hemisected at the 10th thoracic level (T10). Minocycline was injected intraperitoneally, and was administered 30 minutes prior surgery and every second postoperative day until sacrifice 28 days after surgery. Motor recovery was assessed via the Basso-Beattie-Bresnahan test. Mechanical hyperalgesia was measured throughout the 28-day post-operative course via the von Frey test. Microglial and astrocyte activation was assessed by immunohistochemical staining for ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) at two sites: at the level of hemisection and at the 5th lumbar level (L5). Results : In rats, spinal cord hemisection reduced locomotor function and induced a mechanical hyperalgesia of the ipsilateral hind limb. The expression of Iba1 and GFAP was also increased in the dorsal and ventral horns of the spinal cord at the site of hemisection and at the L5 level. Intraperitoneal injection of minocycline facilitated overall motor recovery and attenuated mechanical hyperalgesia. The expression of Iba1 and GFAP in the spinal cord was also reduced in rats treated with minocycline. Conclusion : By inhibiting microglia and astrocyte activation, minocycline may facilitate motor recovery and attenuate mechanical hyperalgesia in individuals with spinal cord injuries.

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Section: Discussionmentioning

confidence: 99%

The Effect of Minocycline on Motor Neuron Recovery and Neuropathic Pain in a Rat Model of Spinal Cord Injury

Cho

Cheong

Yang

et al. 2011

J Korean Neurosurg Soc

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“…At the start of studies, rats in the NRC groups weighed 250-300 g, and the FJD groups had larger weights (350-400 g) to accommodate the customized injury device for that model. [19][20][21][22][23][24][25] All procedures were performed under inhalation anesthesia (4% isoflurane for induction, 2% for maintenance). Surgical procedures for imposing NRC or FJD and shams were previously described.…”

Section: Methodsmentioning

confidence: 99%

“…Surgical procedures for imposing NRC or FJD and shams were previously described. 20,21,[23][24][25] FJD-sham procedures involved attachment to the loading device but no distraction was applied across the joint. [19][20][21] Procedures for NRC-sham were the same as its surgery with nerve root exposure via laminectomy but no compression.…”

Section: Methodsmentioning

confidence: 99%

“…1,18 Our lab has developed separate pain models in the rat that mimic the injury and pain symptoms observed in human neck pain patients with facet-mediated whiplash injuries [19][20][21][22] and cervical radiculopathy. [22][23][24][25] Specifically, distraction of the bilateral facet joints and their capsules that simulates joint loading during whiplash induces significant sustained mechanical allodynia and hyperalgesia in both the shoulders and forepaws. [19][20][21][22] In addition, a transient compression of the unilateral cervical dorsal root also produces significant behavioral hypersensitivity in the ipsilateral forepaw.…”

mentioning

confidence: 99%

“…[19][20][21][22] In addition, a transient compression of the unilateral cervical dorsal root also produces significant behavioral hypersensitivity in the ipsilateral forepaw. [22][23][24][25] These and other injury models have been used as platforms to elucidate relationships between tissue injury, pain, and mechanisms of nociception. In fact, several models of cancer, inflammatory, and repetitive strain injuryinduced pain in the rodent have also evaluated motor function via measurements of forelimb grip force and reach rate.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Impaired performance on the angle board test is induced in a model of painful whiplash injury but is only transient in a model of cervical radiculopathy

Dunk

Nicholson

Winkelstein

2010

Journal Orthopaedic Research

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Although clinical studies report motor impairment associated with some painful injuries of the neck, assessment of motor function in animal models has been largely limited only to studies of direct trauma to the nervous system. The incline plane test was modified to evaluate motor function in two rodent pain models of facet joint distraction (FJD) and nerve root compression (NRC) injury (n ¼ 5/group). Sham groups were also included as controls. Motor function was measured using the modified inclined plane test with rats facing downward before surgery (baseline) and following surgery on days corresponding to when mechanical sensitivity is established and remains elevated. Mean baseline values of the board angle inducing slip for FJD (45.8 AE 3.18) was significantly greater ( p ¼ 0.014) than that for NRC (43.5 AE 2.58), but baseline measurements did not vary for either group over time. No changes in motor function were found for shams. Motor function after FJD significantly decreased ( p < 0.001) at days 1 and 7 after injury. In contrast, at day 1 after NRC injury, slip occurred at significantly lower ( p ¼ 0.0016) incline angles, but returned to baseline levels by day 7. These results show motor function impairment is induced following painful FJD and suggest the incline plane test offers utility to evaluate functional deficits in painful injuries. ß

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Spinal microglial proliferation is evident in a rat model of painful disc herniation both in the presence of behavioral hypersensitivity and following minocycline treatment sufficient to attenuate allodynia

Rothman

Guarino

Winkelstein

2009

J of Neuroscience Research

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Although spinal glia acquire a reactive profile in radiculopathy, glial cell proliferation remains largely unstudied. This study investigated spinal glial proliferation in a model simulating painful disc herniation; the C7 nerve root underwent compression and chromic gut suture exposure or sham procedures. A subset of injured rats received minocycline injections prior to injury. Allodynia was assessed and bromodeoxyuridine (BrdU) was injected 2 hr before tissue harvest on day 1 or 3. Spinal cell proliferation and phenotype identification were assayed by fluorescent colabeling with antibodies to BrdU and either glial fibrillary acidic protein (astrocytes) or Iba1 (microglia). At day 1, ipsilateral allodynia was significantly increased (P < 0.001) for injury over sham. Minocycline treatment significantly decreased ipsilateral allodynia to sham levels at day 1 (P < 0.001). At day 3, ipsilateral allodynia remained and contralateral allodynia was also present for injury (P< 0.003) over sham. The number of BrdU-positive cells in the ipsilateral spinal dorsal horn at day 1 after injury was significantly elevated (P < 0.001) over sham. Approximately 70% of BrdU-positive cells labeled positively for Iba1; dividing microglia were significantly increased (P < 0.004) in the ipsilateral dorsal horn at day 1 following injury compared with sham. Spinal cellular proliferation after injury was not changed by minocycline injection. By day 3, the number of BrdU-positive cells had returned to sham levels bilaterally. Data indicate that spinal microglia proliferate after injury but that proliferation is not abolished by minocycline treatment that attenuates allodynia, indicating that spinal microglial proliferation may be related to injury and may not be linked to changes in sensory perception.

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Chemical and mechanical nerve root insults induce differential behavioral sensitivity and glial activation that are enhanced in combination

Abstract: Rothman, S. M., & Winkelstein, B. A. (2007). Chemical and mechanical nerve root insults induce differential behavioral sensitivity and glial activation that are enhanced in combination. Retrieved from

Cited by 53 publications

References 72 publications

The Effect of Minocycline on Motor Neuron Recovery and Neuropathic Pain in a Rat Model of Spinal Cord Injury

The Effect of Minocycline on Motor Neuron Recovery and Neuropathic Pain in a Rat Model of Spinal Cord Injury

Impaired performance on the angle board test is induced in a model of painful whiplash injury but is only transient in a model of cervical radiculopathy

Spinal microglial proliferation is evident in a rat model of painful disc herniation both in the presence of behavioral hypersensitivity and following minocycline treatment sufficient to attenuate allodynia

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