The Effect of Electroconvulsive Treatment on Thermal Hyperalgesia and Mechanical Allodynia in a Rat Model of Peripheral Neuropathy

Background Preclinical studies involving animal models are essential for understanding the underlying mechanisms of diabetic neuropathic pain. Methods Rats were divided into four groups: two controls and two experimental. Diabetes mellitus was induced by streptozotocin (STZ) injection in two experimental groups. The first group involved one sham operation. The second group involved one latex tube encircling the sciatic nerve. The vehicle-injection rats were used as two corresponding control groups: sham operation and encircled nerves. By the third week, STZ-injected rats with encircled nerves were further divided into three subgroups: one involving continuing observation and the other two involving decompression (removal of the latex tube) at different time points (third week and fifth week). Weight and blood glucose were monitored, and behavioral analysis, including paw withdrawal threshold (PWT) and latency, was performed every week during the experimental period (7 weeks). Results Hyperglycemia was induced in all STZ-injected rats. A significant increase in weight was observed in the control groups when compared with the experimental groups. By the third week, more STZ-injected rats with encircled nerves developed mechanical allodynia than those without (P < 0.05), while no significant difference was noted (P > 0.05) on the incidence of thermal hyperalgesia. Mechanical allodynia, but not thermal hyperalgesia, could be ameliorated by the removal of the latex tube at an early stage (third week). Conclusion With the combined use of a latex tube and STZ injection, a stable rat model of painful diabetic peripheral neuropathy (DPN) manifesting both thermal hyperalgesia and mechanical allodynia has been established.

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A rat model of full thickness thermal injury characterized by thermal hyperalgesia, mechanical allodynia, pronociceptive peptide release and tramadol analgesia

Burns ◽

10.1016/j.burns.2013.10.011 ◽

2014 ◽

Vol 40 (4) ◽

pp. 759-771 ◽

Cited By ~ 21

Author(s):

Marcie Fowler ◽

John L. Clifford ◽

Thomas H. Garza ◽

Terry M. Slater ◽

Helen M. Arizpe ◽

...

Keyword(s):

Rat Model ◽

Mechanical Allodynia ◽

Thermal Injury ◽

Thermal Hyperalgesia ◽

Full Thickness ◽

Peptide Release

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Preconditioning with hydrogen sulfide prevents bone cancer pain in rats through a proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway

Experimental Biology and Medicine ◽

10.1177/1535370217740859 ◽

2017 ◽

Vol 243 (1) ◽

pp. 57-65 ◽

Cited By ~ 3

Author(s):

Li Zhuang ◽

Ke Li ◽

Gaowei Wang ◽

Tao Shou ◽

Chunlin Gao ◽

...

Keyword(s):

Spinal Cord ◽

Cancer Pain ◽

Rat Model ◽

Mechanical Allodynia ◽

Antinociceptive Effect ◽

Thermal Hyperalgesia ◽

Bone Cancer ◽

Bone Cancer Pain ◽

Kinase Pathway

Bone cancer pain (BCP) is a severe type of hyperpathic pain occurring with primary bone tumors or advanced cancers which metastasize to bones. BCP can detrimentally reduce quality of life and presents a challenge to modern medicine. Studies have shown that exogenous H2S may act as a neuroprotectant to protect against some diseases in central nervous system. The preset study aimed to investigate the antinociceptive effect of H2S in BCP. We first measured the changes of serum H2S in patients with BCP and analyzed the relationship between them, then investigated the effect of H2S preconditioning on BCP, and explored the mechanism in rat model. Our results revealed that serum H2S level was negatively correlated with pain scores. In the rat model of BCP, preconditioning with H2S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. The mechanism of H2S preconditioning may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. Impact statement Bone cancer pain (BCP) significantly decreases the life quality of patients or their life expectancy and causes a severe health burden to the society. However, as the exact mechanism of BCP is still poorly understood, no effective treatment has been developed yet. There are some pain medicines now, but they have some inevitable side effects. Additional therapeutic strategies are urgently needed. First, we revealed that preconditioning with H2S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. Second, the mechanism of H2S preconditioning was elucidated. It may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. This novel finding may significantly help us to understand the difference between the roles of endogenous H2S and exogenous H2S in the development of BCP and present us a new strategy of pain management.

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Nuclear PPAR-γ Activation Modulates Inflammation and Oxidative Stress in Attenuating Chemotherapy-Induced Neuropathic Pain in Vivo

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i38b32112 ◽

2021 ◽

pp. 167-179

Author(s):

Haritha Pasupulati ◽

Satyanarayana S. V. Padi ◽

Sujatha Dodoala ◽

Prasad V. S. R. G. Koganti

Keyword(s):

Oxidative Stress ◽

Spinal Cord ◽

Neuropathic Pain ◽

Peripheral Neuropathy ◽

Mechanical Allodynia ◽

Antinociceptive Effect ◽

Thermal Hyperalgesia ◽

Ppar Γ ◽

Markers Of Inflammation ◽

And Oxidative Stress

Background: Paclitaxel-induced painful neuropathy is a major dose-limiting side effect and can persist for up to two years after completing treatment that greatly affects both the course of chemotherapy and quality of life in cancer patients. Peroxisome proliferator-activated receptor (PPAR)-γ belongs to a family of nuclear receptors known for their transcriptional and regulatory roles in metabolism, inflammation, and oxidative stress. However, the role of PPAR-γ activation on paclitaxel-induced neuropathic pain is not yet known. Objective: To investigate whether pioglitazone, a PPAR-γ agonist reduce paclitaxel-induced neuropathic pain and to elucidate underlying mechanisms. Methodology: Peripheral neuropathy was induced by administration of paclitaxel (2 mg/kg per injection) intraperitoneally on four alternate days (days 0, 2, 4, 6). Thermal hyperalgesia and mechanical allodynia were assessed and the markers of inflammation and nitroso-oxidative stress were estimated. Results: Pioglitazone did not induce hypoalgesia and had no effect on locomotor activity. Repeated oral administration of pioglitazone (10 and 20 mg/kg,) for 2 weeks started 14 days after paclitaxel injection markedly attenuated paw withdrawal responses to thermal (hyperalgesia) and mechanical (allodynia) stimuli. Further, pioglitazone administration significantly reduced elevated level of pro-inflammatory cytokine, TNF-α, in both the dorsal root ganglia and the spinal cord accompanied by marked decrease in oxidative stress parameters as well as increase in activity of antioxidant defense enzyme, superoxide dismutase, in the spinal cord after paclitaxel injection. Conclusion: The results of the present study demonstrate that pioglitazone, a PPAR-γ agonist exerted antinociceptive effect in paclitaxel-induced neuropathic pain through inhibiting neuroimmune inflammation in both the periphery and spinal cord and by reducing nitroso-oxidative stress in spinal cord. Our findings strongly suggest pharmacological activation of PPAR-g as a promising therapeutic target in paclitaxel-induced peripheral neuropathy and provide rationale for the clinical evaluation.

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Pre-injury lidocaine treatment prevents thermal hyperalgesia and cutaneous thermal abnormalities in a rat model of peripheral neuropathy

Pain ◽

10.1016/0304-3959(94)00120-4 ◽

1995 ◽

Vol 61 (1) ◽

pp. 3-10 ◽

Cited By ~ 35

Author(s):

Maria Luisa Sotgiu ◽

Anna Castagna ◽

Marco Lacerenza ◽

Paolo Marchettini

Keyword(s):

Peripheral Neuropathy ◽

Rat Model ◽

Thermal Hyperalgesia

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Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model of inflammatory pain

Life Sciences ◽

10.1016/j.lfs.2006.07.031 ◽

2006 ◽

Vol 79 (24) ◽

pp. 2311-2319 ◽

Cited By ~ 104

Author(s):

Bora Inceoglu ◽

Steven L. Jinks ◽

Kara R. Schmelzer ◽

Troy Waite ◽

In Hae Kim ◽

...

Keyword(s):

Rat Model ◽

Inflammatory Pain ◽

Mechanical Allodynia ◽

Epoxide Hydrolase ◽

Thermal Hyperalgesia ◽

Soluble Epoxide Hydrolase

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Long-lasting effect of transcutaneous electrical nerve stimulation on the thermal hyperalgesia in the rat model of peripheral neuropathy

Journal of the Neurological Sciences ◽

10.1016/s0022-510x(03)00038-8 ◽

2003 ◽

Vol 211 (1-2) ◽

pp. 43-47 ◽

Cited By ~ 6

Author(s):

Takaya Inoue ◽

Makoto Takenoshita ◽

Masahiko Shibata ◽

Mitsuhiro Nishimura ◽

Gaku Sakaue ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Rat Model ◽

Nerve Stimulation ◽

Transcutaneous Electrical Nerve Stimulation ◽

Thermal Hyperalgesia ◽

Electrical Nerve Stimulation ◽

Lasting Effect

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Loss of spinal μ-opioid receptor is associated with mechanical allodynia in a rat model of peripheral neuropathy

Pain ◽

10.1016/j.pain.2006.02.017 ◽

2006 ◽

Vol 123 (1) ◽

pp. 117-126 ◽

Cited By ~ 22

Author(s):

Seung Keun Back ◽

Jaehee Lee ◽

Seung Kil Hong ◽

Heung Sik Na

Keyword(s):

Peripheral Neuropathy ◽

Opioid Receptor ◽

Rat Model ◽

Mechanical Allodynia ◽

Μ Opioid Receptor

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Antiallodynic and anti-inflammatory effects of intrathecal R-PIA in a rat model of vincristine-induced peripheral neuropathy

Korean Journal of Anesthesiology ◽

10.4097/kja.19481 ◽

2020 ◽

Vol 73 (5) ◽

pp. 434-444 ◽

Cited By ~ 1

Author(s):

Kyungmi Kim ◽

Wonyeong Jeong ◽

In Gu Jun ◽

Jong Yeon Park

Keyword(s):

Peripheral Neuropathy ◽

Rat Model ◽

Thermal Hyperalgesia ◽

Mechanical Hyperalgesia ◽

Cold Allodynia ◽

Adenosine A1 Receptors ◽

Tnf Α ◽

Adenosine A1 ◽

Α Level ◽

Antiallodynic Effect

Background: Studies investigating the correlation between spinal adenosine A1 receptors and vincristine-induced peripheral neuropathy (VIPN) are limited. This study explored the role of intrathecal N6-(2-phenylisopropyl)-adenosine R-(-)isomer (R-PIA) in the rat model of VIPN. Methods: Vincristine (100 μg/kg) was intraperitoneally administered for 10 days (two 5-day cycles with a 2-day pause) and VIPN was induced in rats. Pain was assessed by evaluating mechanical hyperalgesia, mechanical dynamic allodynia, thermal hyperalgesia, cold allodynia, and mechanical static allodynia. Biochemically, tumor necrosis factor-alpha (TNF-α) level and myeloperoxidase (MPO) activity were measured in the tissue from beneath the sciatic nerve.Results: Vincristine administration resulted in the development of cold allodynia, mechanical hyperalgesia, thermal hyperalgesia, mechanical dynamic allodynia, and mechanical static allodynia. Intrathecally administered R-PIA (1.0 and 3.0 μg/10 μl) reversed vincristine-induced neuropathic pain (cold and mechanical static allodynia). The attenuating effect peaked 15 min after intrathecal administration of R-PIA after which it decreased until 180 min. However, pretreatment with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 μg/10 μl) 15 min before intrathecal R-PIA administration significantly attenuated the antiallodynic effect of R-PIA. This antiallodynic effect of intrathecal R-PIA may be mediated through adenosine A1 receptors in the spinal cord. Intrathecally administered R-PIA also attenuated vincristine-induced increases in TNF-α level and MPO activity. However, pretreatment with intrathecal DPCPX significantly reversed this attenuation.Conclusions: These results suggest that intrathecally administered R-PIA attenuates cold and mechanical static allodynia in a rat model of VIPN, partially due to its anti-inflammatory actions.

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