Analgesic Effects of Sokeikakketsuto on Chemotherapy-Induced Mechanical Allodynia and Cold Hyperalgesia in Rats

Objective Ideally, disease-modifying osteoarthritis (OA) drugs (DMOAD) should combine chondroprotective, anti-inflammatory, and analgesic effects in a single molecule. A fusion protein of interleukin-4 (IL-4) and IL-10 (IL4-10 FP) possesses these combined effects. In this study, the DMOAD activity of rat IL4-10 FP (rIL4-10 FP) was tested in a rat model of surgically induced OA under metabolic dysregulation. Design rIL4-10 FP was produced with HEK293F cells. Bioactivity of purified rIL4-10 FP was determined in a whole blood assay. Male Wistar rats ( n = 20) were fed a high-fat diet (HFD) to induce metabolic dysregulation. After 12 weeks, OA was induced according to the Groove model. Two weeks after OA induction, rats were randomly divided into 2 groups and treated with 10 weekly, intra-articular injections of either rIL4-10 FP ( n = 10) or phosphate buffered saline (PBS; n = 10). Possible antibody formation was evaluated using ELISA, cartilage degeneration and synovial inflammation were evaluated by histology and mechanical allodynia was evaluated using the von Frey test. Results Intra-articular injections with rIL4-10 FP significantly reduced cartilage degeneration ( P = 0.042) and decreased mechanical allodynia ( P < 0.001) compared with PBS. Only mild synovial inflammation was found (nonsignificant), limiting detection of putative anti-inflammatory effects. Multiple injections of rIL4-10 FP did not induce antibodies against rIL4-10 FP. Conclusion rIL4-10 FP showed chondroprotective and analgesic activity in a rat OA model with moderate cartilage damage, mild synovial inflammation, and pain. Future studies will need to address whether less frequent intra-articular injections, for example, with formulations with increased residence time, would also lead to DMOAD activity.

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Propofol Alleviates Neuropathic Pain Induced by Chronic Contractile Injury by Regulating the Spinal glun2b-p38mapkepac1 Pathway

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/9305076 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Wen Li ◽

Chenguang Qin ◽

JianYong Yan ◽

Qian Zhao ◽

Lu You ◽

...

Keyword(s):

Mechanical Allodynia ◽

Underlying Mechanism ◽

Histopathological Analysis ◽

Immunofluorescence Analysis ◽

Withdrawal Threshold ◽

Analgesic Effects ◽

Isoflurane Group ◽

Dorsal Horns ◽

Patients Experience ◽

Thigh Region

Background. Propofol acts as an intravenous anesthetic cure which is widely used as a therapy for the craniocerebral injury that comprised surgical anesthesia as well as the sedation done in the intensive care units. Propofol is one of the most commonly used and efficient anesthetics where the painful effects are followed by an injection of propofol. In many cases, patients experience pain followed by anxiety, boredom, fear, and even myocardial ischemia. Objective. This study was performed to investigate the underlying mechanism of propofol and its effect on regulating spinal glun2b-p38mapkepac1 pathways in chronic contractile injury. Material and Methods. Contractile injury was performed by ligation around the nerve of the thigh region postanesthesia. Rats were divided into three groups to analyze the changes like mechanical allodynia by the paw withdrawal threshold and histopathological analysis for assessing cellular degradation. L4-L6 from the spinal dorsal horns were isolated and harvested for studying protein expression, by the method of western blotting and immunofluorescence analysis. Results. The pain caused due to mechanical allodynia in the paw region was highest at 1 hour postinduction and lasted for three days postinjury. Pain was significantly less in the group receiving propofol when compared with the isoflurane group for the first two hours of injury. In the propofol group, EPAC1, GluN2B, and p38 MAP K were significantly lower. Conclusion. In the rat model of induced chronic contractile injury, postsurgery there was a suppression of the GluN2B-p38MAPK/EPAC1 signaling pathway in the propofol group. As the p38MAPK/EPAC pathway has a significant role in the postoperative hyperalgesia, thus our experiment suggests that propofol has analgesic effects.

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Dim Light at Night Exposure Induces Cold Hyperalgesia and Mechanical Allodynia in Male Mice

Neuroscience ◽

10.1016/j.neuroscience.2020.03.022 ◽

2020 ◽

Vol 434 ◽

pp. 111-119 ◽

Cited By ~ 2

Author(s):

Jacob R. Bumgarner ◽

William H. Walker ◽

Jennifer A. Liu ◽

James C. Walton ◽

Randy J. Nelson

Keyword(s):

Mechanical Allodynia ◽

Male Mice ◽

Light At Night ◽

Cold Hyperalgesia ◽

Dim Light

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Levo-Tetrahydropalmatine Attenuates Bone Cancer Pain by Inhibiting Microglial Cells Activation

Mediators of Inflammation ◽

10.1155/2015/752512 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Mao-yin Zhang ◽

Yue-peng Liu ◽

Lian-yi Zhang ◽

Dong-mei Yue ◽

Dun-yi Qi ◽

...

Keyword(s):

Spinal Cord ◽

Cancer Pain ◽

Mechanical Allodynia ◽

Thermal Hyperalgesia ◽

Bone Cancer ◽

Microglial Cells ◽

Bone Cancer Pain ◽

Enzyme Linked Immunosorbent Assay ◽

Analgesic Effects ◽

Before And After

Objective. The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI).Methods. Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg) were administrated intragastrically at early phase of postoperation (before pain appearance) and later phase of postoperation (after pain appearance), respectively. The concentrations of TNF-α, IL-1β, and IL-18 in spinal cord were measured by enzyme-linked immunosorbent assay. Western blot was used to test the activation of astrocytes and microglial cells in spinal cord after TCI treatment.Results. TCI treatment induced significant thermal hyperalgesia and mechanical allodynia. Administration of L-THP at high doses significantly prevented and/or reversed bone cancer-related pain behaviors. Besides, TCI-induced activation of microglial cells and the increased levels of TNF-αand IL-18 were inhibited by L-THP administration. However, L-THP failed to affect TCI-induced astrocytes activation and IL-1βincrease.Conclusion. This study suggests the possible clinical utility of L-THP in the treatment of bone cancer pain. The analgesic effects of L-THP on bone cancer pain maybe underlying the inhibition of microglial cells activation and proinflammatory cytokines increase.

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Oxaliplatin-induced neuropathy in the rat: Involvement of oxalate in cold hyperalgesia but not mechanical allodynia

Pain ◽

10.1016/j.pain.2009.09.003 ◽

2009 ◽

Vol 147 (1) ◽

pp. 165-174 ◽

Cited By ~ 122

Author(s):

Mariko Sakurai ◽

Nobuaki Egashira ◽

Takehiro Kawashiri ◽

Takahisa Yano ◽

Hiroaki Ikesue ◽

...

Keyword(s):

Mechanical Allodynia ◽

Cold Hyperalgesia

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Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways

10.20944/preprints201906.0155.v1 ◽

2019 ◽

Author(s):

Kanako Miyano ◽

Seiji Shiraishi ◽

Koichiro Minami ◽

Yuka Sudo ◽

Masami Suzuki ◽

...

Keyword(s):

Protein Kinase ◽

Protein Kinase A ◽

Mechanical Allodynia ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Adenosine Monophosphate ◽

Anchoring Protein ◽

Cold Hyperalgesia ◽

Transient Receptor ◽

Kinase A

Carboplatin, an anticancer drug, often causes chemotherapy-induced peripheral neuropathy (PN). Transient receptor potential ankyrin 1 (TRPA1), a non-selective cation channel, is a polymodal nociceptor expressed in sensory neurons. TRPA1 is involved not only in pain transmission but also in allodynia or hyperalgesia development. However, the effects of TRPA1 on carboplatin-induced PN is unclear. We revealed that carboplatin induced mechanical allodynia and cold hyperalgesia, and the pains observed in carboplatin-induced PN models were significantly suppressed by the TRPA1 antagonist HC-030031 without a change in the level of TRPA1 protein. In cells expressing human TRPA, carboplatin had no effects on changes in intracellular Ca2+ concentration ([Ca2+]i); however, carboplatin pretreatment enhanced the increase in [Ca2+]i induced by the TRPA1 agonist, allyl isothiocyanate (AITC). These effects were suppressed by an inhibitor of protein kinase A (PKA). The PKA activator forskolin enhanced AITC-induced increase in [Ca2+]i and carboplatin itself increased intracellular cyclic adenosine monophosphate (cAMP) levels. Moreover, inhibition of A-kinase anchoring protein (AKAP) significantly decreased carboplatin-induced enhancement of [Ca2+]i induced by AITC and improved carboplatin-induced mechanical allodynia and cold hyperalgesia. These results suggested that carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.

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Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways

International Journal of Molecular Sciences ◽

10.3390/ijms20133271 ◽

2019 ◽

Vol 20 (13) ◽

pp. 3271 ◽

Cited By ~ 2

Author(s):

Kanako Miyano ◽

Seiji Shiraishi ◽

Koichiro Minami ◽

Yuka Sudo ◽

Masami Suzuki ◽

...

Keyword(s):

Protein Kinase ◽

Protein Kinase A ◽

Mechanical Allodynia ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Adenosine Monophosphate ◽

Anchoring Protein ◽

Cold Hyperalgesia ◽

Transient Receptor ◽

Kinase A

Carboplatin, an anticancer drug, often causes chemotherapy-induced peripheral neuropathy (PN). Transient receptor potential ankyrin 1 (TRPA1), a non-selective cation channel, is a polymodal nociceptor expressed in sensory neurons. TRPA1 is not only involved in pain transmission, but also in allodynia or hyperalgesia development. However, the effects of TRPA1 on carboplatin-induced PN is unclear. We revealed that carboplatin induced mechanical allodynia and cold hyperalgesia, and the pains observed in carboplatin-induced PN models were significantly suppressed by the TRPA1 antagonist HC-030031 without a change in the level of TRPA1 protein. In cells expressing human TRPA, carboplatin had no effects on changes in intracellular Ca2+ concentration ([Ca2+]i); however, carboplatin pretreatment enhanced the increase in [Ca2+]i induced by the TRPA1 agonist, allyl isothiocyanate (AITC). These effects were suppressed by an inhibitor of protein kinase A (PKA). The PKA activator forskolin enhanced AITC-induced increase in [Ca2+]i and carboplatin itself increased intracellular cyclic adenosine monophosphate (cAMP) levels. Moreover, inhibition of A-kinase anchoring protein (AKAP) significantly decreased the carboplatin-induced enhancement of [Ca2+]i induced by AITC and improved carboplatin-induced mechanical allodynia and cold hyperalgesia. These results suggested that carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.

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