scholarly journals Role of Muscarinic Receptors in Hypoalgesia Induced by Crocin in Neuropathic Pain Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Hossein Ali Safakhah ◽  
Abbas Ali Vafaei ◽  
Azin Tavasoli ◽  
Simin Jafari ◽  
Ali Ghanbari
Keyword(s):  
Neuropathic Pain ◽  
Muscarinic Receptors ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Thermal Stimulus ◽  
Male Wistar Rats ◽  
Withdrawal Response ◽  
Plantar Test ◽  
Von Frey Filaments

Objective. Crocin as an important constituent of saffron has antineuropathic pain properties; however, the exact mechanism of this effect is not known. The aim of this study was whether the hypoalgesic effect of crocin can be exerted through muscarinic receptors. Materials and Methods. In the present project, 36 male Wistar rats (200 ± 20 g) were used. Animals randomly divided into six groups (sham, neuropathy, neuropathy + crocin, neuropathy + atropine 0.5 mg/kg, neuropathy + atropine 1 mg/kg, and neuropathy + atropine 1 mg/kg + crocin). Neuropathy was induced by the chronic constriction injury (CCI) method on the sciatic nerve. Crocin and atropine was administered intraperitoneally during 14 days following the 14th day after surgery. Pain response was detected every three days, two hours after each injection and 3 days following last injection. Mechanical allodynia and thermal hyperalgesia were detected using the Von Frey filaments and plantar test device, respectively. Results. CCI significantly reduced the paw withdrawal response to mechanical and thermal stimulus ( P < 0.01 and P < 0.05 , respectively). Crocin therapy significantly reduced mechanical allodynia and thermal hyperalgesia induced by CCI ( P < 0.05 ). Atropine pretreatment significantly blocked the hypoalgesic effect of crocin ( P < 0.05 in mechanical allodynia and P < 0.01 in thermal hyperalgesia). Fourteen days administration of atropine alone at a dose of 0.5 mg/kg but not 1 mg/kg significantly reduced CCI-induced mechanical allodynia at day 30 after surgery. Conclusion. Crocin significantly decreased CCI-induced neuropathic pain. The hypoalgesic effect of crocin was blocked by atropine pretreatment, which indicates an important role for muscarinic receptors in the effect of crocin.

scholarly journals The Protective Effect of Bergamot Polyphenolic Fraction (BPF) on Chemotherapy-Induced Neuropathic Pain

2021 ◽  
Vol 14 (10) ◽  
pp. 975
Author(s):  
Sara Ilari ◽  
Filomena Lauro ◽  
Luigino Antonio Giancotti ◽  
Valentina Malafoglia ◽  
Concetta Dagostino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Glutamate Transporter ◽  
Thermal Hyperalgesia ◽  
Chemotherapeutic Agents ◽  
Preventive Strategy ◽  
Polyphenolic Extract ◽  
Thermal Hypersensitivity

Paclitaxel is a chemotherapeutic drug used for cancer treatment. Chemotherapy-induced peripheral neuropathy (CIPN) is a common major dose-limiting side effect of many chemotherapeutic agents, including paclitaxel. CIPN is accompanied by mechanical and thermal hypersensitivity that resolves within weeks, months, or years after drug termination. To date, there is no available preventive strategy or effective treatment for CIPN due to the fact that its etiology has not been fully explained. It is clear that free radicals are implicated in many neurodegenerative diseases and recent studies have shown the important role of oxidative stress in development of CIPN. Here, we observed how, in rats, the administration of a natural antioxidant such as the bergamot polyphenolic extract (BPF), can play a crucial role in reducing CIPN. Paclitaxel administration induced mechanical allodynia and thermal hyperalgesia, which began to manifest on day seven, and reached its lowest levels on day fifteen. Paclitaxel-induced neuropathic pain was associated with nitration of proteins in the spinal cord including MnSOD, glutamine synthetase, and glutamate transporter GLT-1. This study showed that the use of BPF, probably by inhibiting the nitration of crucial proteins involved in oxidative stress, improved paclitaxel-induced pain behaviors relieving mechanical allodynia, thermal hyperalgesia, thus preventing the development of chemotherapy-induced neuropathic pain.

scholarly journals Analgesic Effect of Moxibustion with Different Temperature on Inflammatory and Neuropathic Pain Mice: A Comparative Study

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Wei Zhou ◽  
Ruxue Lei ◽  
Chuanyi Zuo ◽  
Yunqing Yue ◽  
Qin Luo ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Spared Nerve Injury ◽  
Chronic Neuropathic Pain ◽  
Chronic Inflammatory Pain ◽  
Significant Difference ◽  
Different Temperatures

The aim of this study was to determine whether variation of temperature during moxibustion would generate division of analgesic effect. The moxibustion with different temperatures (37°C, 42°C, 47°C, and 52°C) was applied to ST36 acupoint for 30 minutes in chronic inflammatory or neuropathic pain mice. The analgesic effect was evaluated by thermal hyperalgesia test in chronic inflammatory pain and by mechanical allodynia in neuropathic pain, respectively. The results indicated that interventions of moxibustion with different temperature caused different analgesic effect on either chronic inflammatory induced by injection of complete Freund’s adjuvant (CFA) or neuropathic pain induced by spared nerve injury (SNI). In chronic inflammatory pain, different moxibustion temperature generated different intensity of analgesic effect: the higher the better. In chronic neuropathic pain, stronger analgesic effect was found in moxibustion with temperature 47°C or 52°C other than 37°C and 42°C. However, there is no significant difference displayed between moxibustion temperatures 47°C and 52°C or 37°C and 42°C. It implies that the temperature should be taken into account for moxibustion treatment to chronic inflammatory or neuropathic pain.

scholarly journals Effects of Topical Application of Clonidine Cream on Pain Behaviors and Spinal Fos Protein Expression in Rat Models of Neuropathic Pain, Postoperative Pain, and Inflammatory Pain

2007 ◽  
Vol 107 (3) ◽  
pp. 486-494 ◽  
Author(s):  
Chi Li ◽  
Hiroshi Sekiyama ◽  
Masakazu Hayashida ◽  
Kenji Takeda ◽  
Toshinobu Sumida ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Postoperative Pain ◽  
Topical Application ◽  
Inflammatory Pain ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Rat Models ◽  
Pain Behaviors ◽  
Plantar Surface ◽  
Lumbar Spinal

Background Clonidine can effectively reduce pain and/or hypersensitivity. However, the antihypersensitivity effects of clonidine topically applied in cream (CC) have not been investigated. The authors evaluated effects of topical application of CC on pain behaviors and spinal Fos-like immunoreactivity in rats with hypersensitivity. Methods Clonidine (30, 100, and 300 microg/g) was prepared in a cream base. In rat models of neuropathic pain, inflammatory pain, and postoperative pain, the authors evaluated effects of CC (0.1 g), topically applied onto the plantar surface of the injured or uninjured paw, on thermal hyperalgesia and mechanical allodynia to von Frey filaments. The authors also evaluated effects of CC on lumbar spinal Fos-like immunoreactivity. Results In neuropathic rats, CC applied onto the injured paw reduced thermal hyperalgesia and mechanical allodynia dose dependently, whereas CC applied onto the uninjured paw had no effect. The antihypersensitivity effects of CC were antagonized by intraperitoneal yohimbine (10 mg/kg). Further, CC reduced Fos-like immunoreactivity in neuropathic rats. In contrast, CC in a single dose had no effects on hyperalgesia, allodynia, or Fos-like immunoreactivity in rats with inflammatory or postoperative pain. In rats with postoperative pain, CC repeatedly applied for 6 days reduced thermal hyperalgesia, but not mechanical allodynia, in the postoperative days, whereas it had no effects on hyperalgesia or allodynia in those with inflammatory pain. Conclusions Topical CC in concentrations examined significantly reduced hypersensitivity and lumbar spinal Fos-like immunoreactivity in rats with neuropathic pain, probably through activation of peripherally located alpha2 adrenoceptors. However, CC was only partially effective and totally ineffective in rats with postoperative pain and inflammatory pain, respectively.

Antiallodynia and antihyperalgesia effects of ceftriaxone in treatment of chronic neuropathic pain in rats

2013 ◽  
Vol 25 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Valiollah Hajhashemi ◽  
Hossein Hosseinzadeh ◽  
Bahareh Amin
Keyword(s):  
Neuropathic Pain ◽  
Glutamate Uptake ◽  
Thermal Hyperalgesia ◽  
Radiant Heat ◽  
Beta Lactam ◽  
Chronic Neuropathic Pain ◽  
Reference Drug ◽  
Beneficial Effects ◽  
Lactam Antibiotic ◽  
Male Wistar Rats

ObjectiveNeuropathic pain is a chronic and disabling syndrome with complex pathogenesis. It has been suggested that the function of glutamate transporters (GLTs) has a major role in the development of neuropathic pain. This study was performed to evaluate various doses of ceftriaxone, a beta-lactam antibiotic, on the symptoms in the rat chronic constriction injury (CCI) model of neuropathic pain. This drug has been recently introduced as a selective up-regulator and activator of GLT1.MethodsNeuropathy was induced in adult male Wistar rats and animals were treated intraperitoneally with 100–400 mg/kg of ceftriaxone for seven consecutive days immediately after surgery. Gabapentin (100 mg/kg, i.p.) was used as a reference drug. von Frey filaments, acetone drop and radiant heat methods were used to assess mechanical allodynia, thermal allodynia and thermal hyperalgesia, respectively.ResultsCeftriaxone in the repeated doses for 7 days showed significant antiallodynic and antihyperalgesic effects especially at a dose of 200 mg/kg twice a day.ConclusionThe results suggest that ceftriaxone as a modulator of glutamate uptake could provide beneficial effects in the treatment of chronic neuropathic pain, especially allodynia that is less sensitive to the most available drugs.

Comprehensive analysis of neurobehavior associated with histomorphological alterations in a chronic constrictive nerve injury model through use of the CatWalk XT system

2014 ◽  
Vol 120 (1) ◽  
pp. 250-262 ◽  
Author(s):  
Chien-Yi Chiang ◽  
Meei-Ling Sheu ◽  
Fu-Chou Cheng ◽  
Chun-Jung Chen ◽  
Hong-Lin Su ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Mechanical Allodynia ◽  
S100 Protein ◽  
Thermal Hyperalgesia ◽  
Nerve Damage ◽  
Dorsal Spinal Cord ◽  
Sensory Evoked ◽  
Dorsal Spinal

Object Neuropathic pain is debilitating, and when chronic, it significantly affects the patient physically, psychologically, and socially. The neurobehavior of animals used as a model for chronic constriction injury seems analogous to the neurobehavior of humans with neuropathic pain. However, no data depicting the severity of histomorphological alterations of the nervous system associated with graded changes in neurobehavior are available. To determine the severity of histomorphological alteration related to neurobehavior, the authors created a model of chronic constrictive injury of varying intensity in rats and used the CatWalk XT system to evaluate neurobehavior. Methods A total of 60 Sprague-Dawley rats, weighing 250–300 g each, were randomly assigned to 1 of 5 groups that would receive sham surgery or 1, 2, 3, or 4 ligatures of 3-0 chromic gut loosely ligated around the left sciatic nerve. Neurobehavior was assessed by CatWalk XT, thermal hyperalgesia, and mechanic allodynia before injury and periodically after injury. The nerve tissue from skin to dorsal spinal cord was obtained for histomorphological analysis 1 week after injury, and brain evoked potentials were analyzed 4 weeks after injury. Results. Significant differences in expression of nerve growth factor existed in skin, and the differences were associated with the intensity of nerve injury. After injury, expression of cluster of differentiation 68 and tumor necrosis factor–α was increased, and expression of S100 protein in the middle of the injured nerve was decreased. Increased expression of synaptophysin in the dorsal root ganglion and dorsal spinal cord correlated with the intensity of injury. The amplitude of sensory evoked potential increased with greater severity of nerve damage. Mechanical allodynia and thermal hyperalgesia did not differ significantly among treatment groups at various time points. CatWalk XT gait analysis indicated significant differences for print areas, maximum contact maximum intensity, stand phase, swing phase, single stance, and regular index, with sham and/or intragroup comparisons. Conclusions. Histomorphological and electrophysiological alterations were associated with severity of nerve damage. Subtle neurobehavioral differences were detected by the CatWalk XT system but not by mechanical allodynia or thermal hyperalgesia. Thus, the CatWalk XT system should be a useful tool for monitoring changes in neuropathic pain, especially subtle alterations.

scholarly journals Urotensin II inhibitor eases neuropathic pain by suppressing the JNK/NF-κB pathway

2017 ◽  
Vol 232 (2) ◽  
pp. 165-174 ◽  
Author(s):  
Jing Li ◽  
Pan-Pan Zhao ◽  
Ting Hao ◽  
Dan Wang ◽  
Yu Wang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Mechanical Allodynia ◽  
Cyclic Peptide ◽  
Intrathecal Injection ◽  
Thermal Hyperalgesia ◽  
Nuclear Factor Κb ◽  
Neurosecretory System ◽  
Urotensin Ii ◽  
Caudal Neurosecretory System

Urotensin II (U-II), a cyclic peptide originally isolated from the caudal neurosecretory system of fishes, can produce proinflammatory effects through its specific G protein-coupled receptor, GPR14. Neuropathic pain, a devastating disease, is related to excessive inflammation in the spinal dorsal horn. However, the relationship between U-II and neuropathic pain has not been reported. This study was designed to investigate the effect of U-II antagonist on neuropathic pain and to understand the associated mechanisms. We reported that U-II and its receptor GPR14 were persistently upregulated and activated in the dorsal horn of L4–6 spinal cord segments after chronic constriction injury (CCI) in rats. Intrathecal injection of SB657510, a specific antagonist against U-II, reversed CCI-induced thermal hyperalgesia and mechanical allodynia. Furthermore, we found that SB657510 reduced the expression of phosphorylated c-Jun N-terminal kinase (p-JNK) and nuclear factor-κB (NF-κB) p65 as well as subsequent secretion of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). It was also showed that both the JNK inhibitor SP600125 and the NF-κB inhibitor PDTC significantly attenuated thermal hyperalgesia and mechanical allodynia in CCI rats. Our present research showed that U-II receptor antagonist alleviated neuropathic pain possibly through the suppression of the JNK/NF-κB pathway in CCI rats, which will contribute to the better understanding of function of U-II and pathogenesis of neuropathic pain.

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

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.

scholarly journals The Role of Toll-Like Receptor 4 Mediates Microglial Activation during Remifentanil-Induced Hyperalgesia in Rats

2018 ◽  
Author(s):  
Xiang Xiang Chen ◽  
Xin Wei
Keyword(s):  
Mechanical Allodynia ◽  
Microglial Activation ◽  
Cell Activation ◽  
Thermal Hyperalgesia ◽  
Toll Like Receptor ◽  
Sprague Dawley ◽  
Toll Like Receptor 4 ◽  
Withdrawal Threshold ◽  
Incisional Pain

Abstract Background: Opioids can induce a state of nociceptive sensitization, also known as opioid-induced hyperalgesia. Nevertheless, the exact mechanism is still unclear. The following study investigates the role of Toll-like receptor 4 (TLR4) in the microglial activation during remifentanil—induced hyperalgesia in rats’ model of incisional pain. Methods: Mechanical allodynia induced by remifentanil was established in adult male Sprague–Dawley rats with incisional pain. Paw withdrawal threshold (PWT) and paw withdrawal thermal latency (PWTL) were performed to evaluate mechanical and thermal hyperalgesia. The 32-G catheter intrathecal placement was used to deliver a specific TLR4 antagonist (LPS-RS).Western blot analysis was performed to measure the expression of the TLR4 and iba-1, while Immunofluorescence staining was used to investigate the cell type and cell activation. Results：Incisionalpain-remifentanil decreased the PWT and PWTL, upregulated the expression of TLR4 and microglial activation in the spinal cord. On the contrary, the intrathecal delivery of LPS-RS at the dose of 25 μg significantly decreased mechanical allodynia and prevented the upregulation of TLR4 induced by incisional pain-remifentanil Conclusion: These findings suggest that TLR4 signaling pathway has an important role in incisional pain-remifentanil hyperalgesia, and that it could serve as the therapeutic target for persistent postsurgical pain

scholarly journals Evaluation of the GABAA Receptor Expression and the Effects of Muscimol on the Activity of Wide Dynamic Range Neurons Following Chronic Constriction Injury of the Sciatic Nerve in Rats

2021 ◽  
Author(s):  
Mehdi Sadeghi ◽  
◽  
Homa Manaheji ◽  
Jalal Zaringhalam ◽  
Abbas Haghparast ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Gabaa Receptor ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Dynamic Range ◽  
Thermal Hyperalgesia ◽  
Receptor Expression ◽  
Wide Dynamic Range ◽  
Wdr Neurons ◽  
Α1 Subunit

Introduction: The modality of γ-aminobutyric acid receptors (GABAA) in control of dorsal horn neuronal excitability and inhibition of sensory information is ambiguous. The aim of the present study was to investigate the expression of GABAA receptor and the effects of its agonist muscimol on wide dynamic range (WDR) neuronal activity in the chronic constriction injury (CCI) model of neuropathic pain. Methods: Adult male Wistar rats weighing 200 to 250 g were used for the induction of CCI neuropathy. 14 days after surgery, muscimol (0.5, 1, and 2 mg/kg i.p.) was injected. Then, the behavioral tests were performed. Thereafter, the animals were sacrificed, and the lumbar segments of the spinal cords were collected for Western blot analysis of the GABAA receptor α1 subunit expression. The electrophysiological properties of WDR neurons were studied by single unit recordings in separate groups on the 14th day after CCI. Results: The outcomes indicated the development of thermal hyperalgesia and mechanical allodynia after neuropathy; nonetheless, the expression of GABAA receptor α1 subunit did not change significantly. Moreover, the evoked responses of the WDR neurons to electrical, mechanical, and thermal stimuli were significantly increased. 14 days after CCI, muscimol administration decreased thermal hyperalgesia, mechanical allodynia, and hyper-responsiveness of the WDR neurons in CCI rats. Conclusion: It confirms that the modulation of the spinal GABAA receptors after nerve injury can offer further insights to design new therapeutic agents in order to reduce the neuropathic pain symptoms.

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