Behavioral characterization and effect of clinical drugs in a rat model of pain following spinal cord compression

Hama, Aldric; Sagen, Jacqueline

doi:10.1016/j.brainres.2007.09.013

Cited by 48 publications

(59 citation statements)

References 88 publications

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“…In a previous study, 4 weeks following spinal compression injury, the average BassoBeattie-Bresnahan (BBB) locomotor functionality score was about 11 (this scale ranges from 0, no functionality, to 21, normal hindlimb function), which is comparable to scores obtained following a moderate contusive injury (Basso et al, 1995;Hama and Sagen, 2007;Hains and Waxman, 2006). Also, spontaneous bladder function returns within 1-2 days post-compression injury, suggesting a moderate, rather than a severe, SCI.…”

mentioning

confidence: 58%

“…In a separate group of rats (n = 14), a brief compression of a segment of mid-thoracic spinal cord was performed (Hama and Sagen, 2007). Using a dorsal approach, a blunt dissection of the mid-thoracic musculature was made to expose the midthoracic (T5-T6) vertebrae.…”

Section: Surgery Proceduresmentioning

confidence: 99%

“…In the current study we evaluated the efficacy of the nonselective phosphodiesterase (PDE) inhibitor ibudilast, a vasodilator and bronchodilator drug that is used to treat asthma, in a rat model of below-level neuropathic pain following an acute spinal injury (Hama and Sagen, 2007;Kishi et al, 2001). Ibudilast suppresses the release of TNF-a from activated microglia in vitro, through a PDE-mediated mechanism (Ledeboer et al, 2006;Suzumura et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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The Antinociceptive Effect of the Asthma Drug Ibudilast in Rat Models of Peripheral and Central Neuropathic Pain

Hama

Broadhead²,

Lorrain³

et al. 2012

Journal of Neurotrauma

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Ibudilast, an asthma drug, has demonstrated antinociceptive effects in several rat models of peripheral neuropathic pain, and a proposed mechanism of action is the inhibition of release of the cytokine tumor necrosis factor-α (TNF-α) from activated spinal microglia. Spinal glial activation has also been demonstrated in rat models of central neuropathic pain following spinal cord injury (SCI). The current study evaluated the effect of a short course of treatment with ibudilast on SCI-induced pain, and for comparison, following a chronic constriction injury (CCI; the Bennett model) of the sciatic nerve in rats. The effects of ibudilast treatment on spinal (SCI and CCI rats), and nerve tissue (CCI only) TNF-α content were also evaluated. Following an acute midthoracic SCI with a microvascular clip (20-g force), hindpaw withdrawal thresholds were significantly decreased, indicating below-level cutaneous tactile hypersensitivity. Likewise, unilateral loose ligation of the sciatic nerve led to a robust ipsilateral tactile hypersensitivity. Rats were treated with either ibudilast (10 mg/kg IP) or vehicle (2 mL/kg) during the period of robust and steady hindpaw hypersensitivity for each model--CCI rats were treated 14-16 days post-surgery, and SCI rats were treated 30-32 days post-surgery--and tested daily. Ibudilast ameliorated hindpaw hypersensitivity in both SCI and CCI rats, whereas vehicle treatment had no effect. Interestingly, repeated treatment led to increased baseline thresholds, beyond the duration of the drug half-life, suggesting persistent changes in neuropathic pain processing. In SCI rats, an increase in TNF-α content in spinal tissue rostral to the SCI was observed. Ibudilast treatment did not significantly alter this increase. In rats with a CCI, TNF-α content was markedly increased in the ipsilateral sciatic nerve and was partially reduced following ibudilast, but not vehicle, treatment. Ibudilast could be useful for the treatment of neuropathic pain of central as well as peripheral origin.

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confidence: 58%

Section: Surgery Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Antinociceptive Effect of the Asthma Drug Ibudilast in Rat Models of Peripheral and Central Neuropathic Pain

Hama

Broadhead²,

Lorrain³

et al. 2012

Journal of Neurotrauma

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“…Hama and Sagen [48] report that by injecting the nonselective CB receptor agonist WIN 55,212-2 (WIN), SCI-induced mechanical allodynia following a thoracic-level compression SCI was reduced. The emerging role of AEA-specific fatty acid amide hydrolase and 2AG-specific monoacylglycerol lipase as regulators of catabolism and biosynthesis of the CBs is reported [49] .…”

Section: Cannabinoid Receptorsmentioning

confidence: 99%

Yoga: Can It Be Integrated with Treatment of Neuropathic Pain

Telles¹,

Sayal

Nacht

et al. 2017

Integr Med Int

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Background: Neuropathic pain (NP) is a debilitating condition that may result from spinal cord injury (SCI). Nearly 75% of all SCIs result in NP affecting 17,000 new individuals in the United States every year, and an estimated 7-10% of people worldwide. It is caused by damaged or dysfunctional nerve fibers sending aberrant signals to pain centers in the central nervous system causing severe pain that affects daily life and routine. The mechanisms underlying NP are not fully understood, making treatment difficult. Identification of specific molecular pathways that are involved in pain syndromes and finding effective treatments has become a major priority in current SCI research. Yoga has therapeutic applications that may prove beneficial in treating subjects suffering chronically from SCI-induced NP, chronic back and associated pain if necessary experimental data are generated. Summary: This review aims to discuss the implications of various mechanistic approaches of yoga which can be tested by new study designs around various nociceptive molecules including matrix metalloproteinases, cation-dependent chloride transporter (NKCC1), etc. in SCI-induced NP pa-

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“…A micro-vascular clip (Harvard Apparatus, MA) was placed vertically on the exposed thoracic spinal cord for 60 seconds. 11,12 Dura was intact and care was taken not to disturb nearby spinal nerve roots. Following spinal compression, the clip was removed, the muscles sutured shut and the skin closed with 4/0 silk.…”

Section: Surgical Proceduresmentioning

confidence: 99%

Spinal 5-HT3 receptor mediates nociceptive effect on central neuropathic pain; possible therapeutic role for tropisetron

Nasirinezhad

Hosseini

Karami

et al. 2015

The Journal of Spinal Cord Medicine

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Objectives: To test the analgesic effect of 5-HT-3 receptor antagonist, tropisetron, in a clip compression injury model of spinal cord pain in rats. Methods: Four weeks post compression of the spinal cord at lumbar level, tropisetron was administered intrathecally at 100 μg and 150 μg dosages. Behavioral tests were assessed before administration. Fifteen minutes after injection, behavioral tests were repeated. Randall-Sellitto and plantar test was used for mechanical and thermal hyperalgesia, respectively. Mechanical and cold allodynia were evaluated by Von Frey filament and acetone droplets, respectively. The analgesic effect of tropisetron was compared with intrathecal administration of salicylate. Locomotor score was evaluated by Basso, Beattie and Bresnahan (BBB) test every week after spinal cord injury. Results: Intrathecal administration of tropisetron, decreased hyperalgesia and mechanical allodynia, but not cold allodynia were observed after compression of the spinal cord. Conclusion: Blockade of 5-HT-3 receptors by tropisetron at the spinal level induces an antinociceptive effect on chronic central neuropathic pain and suggests that this compound may have potential clinical utility for the management of central neuropathic pain, particularly in patients with hyperalgesia and tactile allodynia.

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Behavioral characterization and effect of clinical drugs in a rat model of pain following spinal cord compression

Cited by 48 publications

References 88 publications

The Antinociceptive Effect of the Asthma Drug Ibudilast in Rat Models of Peripheral and Central Neuropathic Pain

The Antinociceptive Effect of the Asthma Drug Ibudilast in Rat Models of Peripheral and Central Neuropathic Pain

Yoga: Can It Be Integrated with Treatment of Neuropathic Pain

Spinal 5-HT3 receptor mediates nociceptive effect on central neuropathic pain; possible therapeutic role for tropisetron

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