Pharmacological and behavioral characterization of the saphenous chronic constriction injury model of neuropathic pain in rats

Gündüz, Özgür; Oltulu, Cagatay; Guven, Rabia; Buldum, Dilek; Ulugöl, Ahmet

doi:10.1007/s10072-011-0761-7

Cited by 10 publications

(6 citation statements)

References 43 publications

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“…In this study, seven days after CCI, the mice showed a relatively high degree of similarity to other studies published on neuropathic pain in terms of the degrees of allodynia and hyperalgesia, demonstrated by the increased responsiveness to von Frey filaments, cold-plate and plantar test apparatus. Unilateral sciatic nerve ligation induced significant behavioral alterations resulting in ipsilateral mechanical allodynia appearing on the 7th day of the surgery; our results are in accord with Gunduz et al (2011). The cold allodynia induced by CCI peaked on the 7th postoperative day and this is consistent with Tanimoto-Mori et al (2008) and thermal hyperalgesia that was expressed with latency, on the 7th day after operation.…”

Section: Discussionsupporting

confidence: 80%

Antinociceptive effects of matrine on neuropathic pain induced by chronic constriction injury

Wang¹,

Li²,

Linglu³

et al. 2013

Pharmaceutical Biology

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Context: Sophora alopecuroides L. (Leguminosae) is a commonly used Chinese herbal drug that possesses antipyretic, anti-inflammatory and analgesic effects. Among various alkaloids isolated from S. alopecuroides, matrine has been identified as the major bioactive component contributing to a variety of pharmacological effects, and studies have also shown that matrine has an analgesic effect. Objective: To investigate the antinociceptive effects of matrine on neuropathic pain induced by chronic constriction injury (CCI) in mice. Materials and methods: The von Frey, plantar, cold-plate, locomotor activity and rota-rod test were performed to assess the degree of mechanical, radiant, thermal, spontaneous locomotor activity and motor coordination changes respectively, at different time intervals, i.e., one day before surgery and 7, 8, 10, 12 and 14 days post surgery. Matrine was administered from the 8th day after the surgery for seven days.Results: Our present study shows that matrine at the dose of 30 mg/kg i.p. increased the paw withdrawal threshold (0.88 AE 0.16), paw withdrawal latency (7.01 AE 0.11) and the counts of paw withdrawal (19.7 AE 1.15) from the day 8 for the nerve injured paw compared to the CCI group (0.18 AE 0.04, 4.62 AE 0.18, 44.3 AE 2.99, respectively). Matrine, in a dose-dependent effect, was also found to produce a protective role in both plantar and cold-plate tests. The analysis of the effect supports the hypothesis that matrine is useful in neuropathic pain therapy. Discussion and conclusion: The results of this study suggest that matrine could be useful in the treatment of different kinds of neuropathic pains as an adjuvant to conventional medicines.

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Section: Discussionsupporting

confidence: 80%

Antinociceptive effects of matrine on neuropathic pain induced by chronic constriction injury

Wang¹,

Li²,

Linglu³

et al. 2013

Pharmaceutical Biology

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“…For instance, the anti-nociceptive and anti-allodynic effectiveness of GBP has been widely supported by studies in animal models of many types of pain induced by peripheral nerve injury such as spinal nerve ligation [47][48][49][50], chronic compression injury [51][52][53][54][55][56] and spared nerve injury [57,58]. Moreover, GBP has also been demonstrated to have anti-allodynic and anti-hyperalgesic effects in animal models of diabetic neuropathy [29] and postherpetic neuralgia [59].…”

Section: Gabapentinoid Insensitivity In Central Neuropathic Pain Of Tmentioning

confidence: 99%

Gabapentinoid Insensitivity after Repeated Administration is Associated with Down-Regulation of the α2δ-1 Subunit in Rats with Central Post-Stroke Pain Hypersensitivity

Yang

et al. 2016

Neurosci. Bull.

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The a 2 d-1 subunit of the voltage-gated Ca 2? channel (VGCC) is a molecular target of gabapentin (GBP), which has been used as a first-line drug for the relief of neuropathic pain. GBP exerts its anti-nociceptive effects by disrupting trafficking of the a 2 d-1 subunit to the presynaptic membrane, resulting in decreased neurotransmitter release. We previously showed that GBP has an antiallodynic effect in the first two weeks; but this is followed by insensitivity in the later stage after repeated administration in a rat model of central post-stroke pain (CPSP) hypersensitivity induced by intra-thalamic hemorrhage. To explore the mechanisms underlying GBP insensitivity, the cellular localization and time-course of expression of the a 2 d-1 subunit in both the thalamus and spinal dorsal horn were studied in the same model. We found that the a 2 d-1 subunit was mostly localized in neurons, but not astrocytes and microglia. The level of a 2 d-1 protein increased in the first two weeks after injury but then decreased in the third week, when GBP insensitivity occurred. Furthermore, the a 2 d-1 down-regulation was likely caused by later neuronal loss in the injured thalamus through a mechanism other than apoptosis. In summary, the present results suggest that the GBP receptor a 2 d-1 is mainly expressed in thalamic neurons in which it is up-regulated in the early stage of CPSP but this is followed by dramatic down-regulation, which is likely associated with GBP insensitivity after long-term use.Keywords Central post-stroke pain Á Calcium channel a 2 d subunit Á Gabapentinoid Á Thalamic hemorrhagic stroke Á Thalamus Á Spinal dorsal horn

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“…Even most of the powerful painkillers like morphine and other opioid drugs are inadequate; they are generally effective at higher doses when their adverse effects are seen. In general, antidepressants (e. g., amitriptyline and nortriptyline) and some anticonvulsant drugs (e. g., gabapentin, pregabalin) are recommended for first-line treatment of neuropathic pain; however, it is clear that there is a lack of specific medications that effectively treat this indication [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Spinal Serotonin and 5HT6 Receptor Levels During Development of Neuropathy and Influence of Blockade of these Receptors on Thermal Hyperalgesia in Diabetic Mice

2019

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Little is known about the role of 5-HT6 receptors in the pathophysiology of neuropathic pain. The aim of this study is firstly, to investigate the influence of spinal and systemic 5-HT6 receptors on thermal hyperalgesia, one of the most significant symptoms of neuropathy occurring in diabetes; and secondly to determine spinal lumbar serotonin and 5-HT6 receptor levels during development of diabetic neuropathy in mice. Diabetes was produced in Balb/c mice with a single injection of streptozocin (150 mg/kg, i.p.). Using the hot plate test, the 5-HT6 antagonist SB-258585 was given systemically (3, 10, 30 mg/kg) and intrathecally (0.01, 0.1, 1 nmol/mouse) to determine its effect on thermal hyperalgesia. Furthermore, on days 7 and 15 of diabetes, development of thermal hyperalgesia was evaluated in relation to changes in spinal serotonin and 5-HT6 receptor levels by using LC/MS/MS and Western blot analyses, respectively. Two-way analysis of variance and unpaired t-tests were used to evaluate data from hot-plate tests and 5-HT levels/ 5-HT6 receptor expression, respectively. Thermal hyperalgesia was observed in neuropathic mice, starting from day 5 after streptozocin administration. On day 15, systemic, but not intrathecal, SB-258585 attenuated thermal hyperalgesia in neuropathic mice. Spinal serotonin levels did not change during development of hyperalgesia after induction of diabetes, whereas spinal 5-HT6 receptor levels were significantly reduced on days 7 and 15. Our findings show that systemic, but not spinal, blockade of 5-HT6 receptors may exert antihyperalgesic effects in neuropathic mice and suggest that systemic 5-HT6 receptors contribute to the pathophysiology of diabetic neuropathy.

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Pharmacological and behavioral characterization of the saphenous chronic constriction injury model of neuropathic pain in rats

Cited by 10 publications

References 43 publications

Antinociceptive effects of matrine on neuropathic pain induced by chronic constriction injury

Antinociceptive effects of matrine on neuropathic pain induced by chronic constriction injury

Gabapentinoid Insensitivity after Repeated Administration is Associated with Down-Regulation of the α2δ-1 Subunit in Rats with Central Post-Stroke Pain Hypersensitivity

Spinal Serotonin and 5HT6 Receptor Levels During Development of Neuropathy and Influence of Blockade of these Receptors on Thermal Hyperalgesia in Diabetic Mice

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