scholarly journals Zingiber officinale Roscoe Rhizomes Attenuate Oxaliplatin-Induced Neuropathic Pain in Mice

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 548
Author(s):  
Ji Hwan Lee ◽  
Daeun Min ◽  
Donghun Lee ◽  
Woojin Kim
Keyword(s):  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Zingiber Officinale ◽  
Treatment Interruption ◽  
Pcr Analysis ◽  
Cold Allodynia ◽  
Zingiber Officinale Roscoe ◽  
Pre Treatment ◽  
Platinum Derivative ◽  
Viable Treatment

Oxaliplatin is a platinum derivative chemotherapeutic drug widely used against cancers, but even a single treatment can induce a severe allodynia that requires treatment interruption and dose diminution. The rhizome of Zingiber officinale roscoe (Z. officinale, ginger), has been widely used in traditional medicine to treat various diseases causing pain; however, its effect against oxaliplatin-induced neuropathic pain has never been assessed. In mice, a single oxaliplatin (6 mg/kg, i.p.) treatment induced significant cold and mechanical allodynia. Cold and mechanical allodynia were assessed by acetone drop and von Frey filament tests, respectively. Water extracts of Z. officinale (100, 300, and 500 mg/kg, p.o.) significantly attenuated both cold and mechanical allodynia induced by oxaliplatin. Intrathecal pre-treatment with the antagonist 5-HT1A (NAN-190, i.t., 1 μg), but not with the antagonist 5-HT2A (ketanserin, i.t., 1 μg), significantly blocked the analgesic effect of Z. officinale against both cold and mechanical allodynia. However, 5-HT3 antagonist (MDL-72222, i.t., 15 μg) administration only blocked the anti-allodynic effect of Z. officinale against cold allodynia. Real-time PCR analysis demonstrated that Z. officinale significantly increased the mRNA expression of the spinal 5-HT1A receptor that was downregulated after oxaliplatin injection. These results suggest that Z. officinale may be a viable treatment option for oxaliplatin-induced neuropathic pain.

scholarly journals JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice

2021 ◽  
Vol 22 (16) ◽  
pp. 8811
Author(s):  
Ji Hwan Lee ◽  
Hyunseung Ji ◽  
Seong-Gyu Ko ◽  
Woojin Kim
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Zingiber Officinale ◽  
Pcr Analysis ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Antagonist ◽  
Transient Receptor

Oxaliplatin, a well-known chemotherapeutic agent, can induce severe neuropathic pain, which can seriously decrease the quality of life of patients. JI017 is an herb mixture composed of Aconitum carmichaelii, Angelica gigas, and Zingiber officinale. Its anti-tumor effect has been reported; however, the efficacy of JI017 against oxaliplatin-induced allodynia has never been explored. Single oxaliplatin injection [6 mg/kg, intraperitoneal, (i.p.)] induced both cold and mechanical allodynia, and oral administration of JI017 (500 mg/kg) alleviated cold but not mechanical allodynia in mice. Real-time polymerase chain reaction (PCR) analysis demonstrated that the upregulation of mRNA of spinal transient receptor potential vanilloid 1 (TRPV1) and astrocytes following oxaliplatin injection was downregulated after JI017 treatment. Moreover, TRPV1 expression and the activation of astrocytes were intensely increased in the superficial area of the spinal dorsal horn after oxaliplatin treatment, whereas JI017 suppressed both. The administration of TRPV1 antagonist [capsazepine, intrathecal (i.t.), 10 μg] attenuated the activation of astrocytes in the dorsal horn, demonstrating that the functions of spinal TRPV1 and astrocytes are closely related in oxaliplatin-induced neuropathic pain. Altogether, these results suggest that JI017 may be a potent candidate for the management of oxaliplatin-induced neuropathy as it decreases pain, spinal TRPV1, and astrocyte activation.

scholarly journals Tongluo Zhitong Prescription Alleviates Allodynia, Hyperalgesia, and Dyskinesia in the Chronic Constriction Injury Model of Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Zhiyong Wang ◽  
Jianwei Wang ◽  
Lihua Qin ◽  
Weiguang Zhang
Keyword(s):  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Catgut Suture ◽  
Cold Allodynia ◽  
Injury Model ◽  
Neuropathic Pain Model ◽  
Gait Function ◽  
Chronic Constriction Injury Model ◽  
Heat Hyperalgesia

Neuropathic pain is common in clinical practice. Exploration of new drug therapeutics has always been carried out for more satisfactory effects and fewer side-effects. In the present study, we aimed to investigate effects of Tongluo Zhitong Prescription (TZP), a compounded Chinese medicine description, on neuropathic pain model of rats with chronic constriction injury (CCI). The CCI model was established by loosely ligating sciatic nerve with catgut suture, proximal to its trifurcation. The static and dynamic allodynia, heat hyperalgesia, mechanical allodynia, cold allodynia, and gait were assessed. Our results showed that TZP alleviated CCI-induced static and dynamic allodynia, suppressed heat hyperalgesia and cold and mechanical allodynia, and improved gait function. These results suggest that TZP could alleviate neuropathic pain. Further experiments are needed to explore its mechanisms.

scholarly journals Delta Opioid Receptor in Astrocytes Contributes to Neuropathic Cold Pain and Analgesic Tolerance in Female Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
David Reiss ◽  
Hervé Maurin ◽  
Emilie Audouard ◽  
Miriam Martínez-Navarro ◽  
Yaping Xue ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Opioid Receptor ◽  
Mechanical Allodynia ◽  
Conditional Knockout ◽  
Delta Opioid Receptor ◽  
Cold Pain ◽  
Analgesic Tolerance ◽  
Cold Allodynia ◽  
Female Mice ◽  
Control Pain

Background: The delta opioid receptor (DOR) contributes to pain control, and a major challenge is the identification of DOR populations that control pain, analgesia, and tolerance. Astrocytes are known as important cells in the pathophysiology of chronic pain, and many studies report an increased prevalence of pain in women. However, the implication of astrocytic DOR in neuropathic pain and analgesia, as well as the influence of sex in this receptor activity, remains unknown.Experimental Approach: We developed a novel conditional knockout (cKO) mouse line wherein DOR is deleted in astrocytes (named GFAP-DOR-KO), and investigated neuropathic mechanical allodynia as well as analgesia and analgesic tolerance in mutant male and female mice. Neuropathic cold allodynia was also characterized in mice of both sexes lacking DOR either in astrocytes or constitutively.Results: Neuropathic mechanical allodynia was similar in GFAP-DOR-KO and floxed DOR control mice, and the DOR agonist SNC80 produced analgesia in mutant mice of both sexes. Interestingly, analgesic tolerance developed in cKO males and was abolished in cKO females. Cold neuropathic allodynia was reduced in mice with decreased DOR in astrocytes. By contrast, cold allodynia was exacerbated in full DOR KO females.Conclusions: These findings show that astrocytic DOR has a prominent role in promoting cold allodynia and analgesic tolerance in females, while overall DOR activity was protective. Altogether this suggests that endogenous- and exogenous-mediated DOR activity in astrocytes worsens neuropathic allodynia while DOR activity in other cells attenuates this form of pain. In conclusion, our results show a sex-specific implication of astrocytic DOR in neuropathic pain and analgesic tolerance. These findings open new avenues for developing tailored DOR-mediated analgesic strategies.

scholarly journals Zingiber officinale Roscoe rhizome extract alleviates neuropathic pain by inhibiting neuroinflammation in mice

Phytomedicine ◽  
2020 ◽  
Vol 78 ◽  
pp. 153307 ◽  
Author(s):  
Vittoria Borgonetti ◽  
Paolo Governa ◽  
Marco Biagi ◽  
Federica Pellati ◽  
Nicoletta Galeotti
Keyword(s):  
Neuropathic Pain ◽  
Zingiber Officinale ◽  
Zingiber Officinale Roscoe

Activation of TRPM8 cold receptor triggers allodynia-like behavior in spinally injured rats

2013 ◽  
Vol 4 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Tianle Gao ◽  
Jingxia Hao ◽  
Zsuzsanna Wiesenfeld-Hallin ◽  
Xiao-Jun Xu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Topical Application ◽  
Mechanical Allodynia ◽  
Trp Channels ◽  
Cold Stimulation ◽  
Cold Allodynia ◽  
Nociceptive Responses ◽  
Cord Injury

AbstractAimsPain in response to innocuous cold stimulation (cold allodynia) is a common symptom in patients with neuropathic pain. Cold allodynia is difficult to treat and its mechanisms are poorly understood. Several transient receptor potential (TRP) channels have been shown to be the molecular sensors for cold stimulation in a temperature-dependent manner, but the contribution of various TRP channels in mediating cold allodynia in neuropathic pain is unclear. We have previously shown that spinally injured rats developed neuropathic pain-like behaviors, including marked cold allodynia. We now assessed the role of TRP channels in mediating cold allodynia in rats after ischemic spinal cord injury.Methods Methods: Spinal cord injury was produced using a photochemical method. The mechanical allodynia was assessed by examining the vocalization thresholds to graded mechanical touch/pressure applied with von Frey hairs. Temperature controlled cold stimulation was produced by a Peltier thermode (active surface 25 mm × 50 mm) connected to a MSA Thermal Simulator (Somedic, Sweden) with baseline temperature of 32 °C. The rate of temperature change was 0.5 °C/s. The temperature required to elicit cold allodynia was examined. The responses of the rats to topical application of icilin or menthol, agonists of transient receptor potential melastain 8 (TRPM8), were also studied.ResultsNormal rats did not exhibit nociceptive responses to cooling stimulation to the trunk and back area (minimal temperature +6°C) and they also did not react aversively to topical application of icilin or menthol. After spinal cord injury, the rats developed mechanical allodynia at the trunk and back just rostral to the dermatome of the injured spinal segments. In the same area, rats exhibited significant nociceptive responses to cooling from day 1 after injury, lasting for at least 70 days which is the longest time of observation. For the first two weeks after injury, the majority of spinally injured rats had a nociceptive response to cooling above 17°C. At day 70, about 50% of rats responded to cooling above 17 °C. Topical application of 400 μM icilin or 4mM menthol also elicited pain-like responses in spinally injured rats and these two cold mimetics also significantly exacerbated existing mechanical allodynia.ConclusionOur results showed that activation of the TRPM8 channel by menthol or icilin triggers allodynia in spinally injured rats and increases, rather than decreases, mechanical allodynia. TRPM8 channels which respond to cooling above 17 ° C may be involved at least in part in mediating cold allodynia in the rat model of neuropathic spinal cord injury pain.ImplicationsThe work introduced a method of quantitative testings of responses of rats to cold stimulation and may contribute to the understanding of mechanisms of cold allodynia after injury to the nervous system.

scholarly journals Local Sympathectomy Promotes Anti-inflammatory Responses and Relief of Paclitaxel-induced Mechanical and Cold Allodynia in Mice

2020 ◽  
Vol 132 (6) ◽  
pp. 1540-1553
Author(s):  
Raquel Tonello ◽  
Wenrui Xie ◽  
Sang Hoon Lee ◽  
Min Wang ◽  
Xiaojuan Liu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Growth Factor ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Sympathetic Blockade ◽  
Male Mice ◽  
Cold Allodynia

Abstract Background Patients undergoing cancer treatment often experience chemotherapy-induced neuropathic pain at their extremities, for which there is no U.S. Food and Drug Administration–approved drug. The authors hypothesized that local sympathetic blockade, which is used in the clinic to treat various pain conditions, can also be effective to treat chemotherapy-induced neuropathic pain. Methods A local sympathectomy (i.e., cutting the ipsilateral gray rami entering the spinal nerves near the L3 and L4 dorsal root ganglia) was performed in mice receiving intraperitoneal injections every other day of the chemotherapeutic drug paclitaxel. Sympathectomy effects were then assessed in chemotherapy-induced pain-like behaviors (i.e., mechanical and cold allodynia) and neuroimmune and electrophysiologic responses. Results Local microsympathectomy produced a fast recovery from mechanical allodynia (mean ± SD: sympathectomy vs. sham at day 5, 1.07 ± 0.34 g vs. 0.51 ± 0.17g, n = 5, P = 0.030 in male mice, and 1.08 ± 0.28 g vs. 0.62 ± 0.16 g, n = 5, P = 0.036 in female mice) and prevented the development of cold allodynia in both male and female mice after paclitaxel. Mechanistically, microsympathectomy induced transcriptional increases in dorsal root ganglia of macrophage markers and anti-inflammatory cytokines, such as the transforming growth factor-β. Accordingly, depletion of monocytes/macrophages and blockade of transforming growth factor-β signaling reversed the relief of mechanical allodynia by microsympathectomy. In particular, exogenous transforming growth factor-β was sufficient to relieve mechanical allodynia after paclitaxel (transforming growth factor-β 100 ng/site vs. vehicle at 3 h, 1.21 ± 0.34g vs. 0.53 ± 0.14 g, n = 5, P = 0.001 in male mice), and transforming growth factor-β signaling regulated neuronal activity in dorsal root ganglia. Conclusions Local sympathetic nerves control the progression of immune responses in dorsal root ganglia and pain-like behaviors in mice after paclitaxel, raising the possibility that clinical strategies already in use for local sympathetic blockade may also offer an effective treatment for patients experiencing chemotherapy-induced neuropathic pain. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

scholarly journals The Analgesic Effect of Venlafaxine and Its Mechanism on Oxaliplatin-Induced Neuropathic Pain in Mice

2019 ◽  
Vol 20 (7) ◽  
pp. 1652 ◽  
Author(s):  
Daxian Li ◽  
Ji Lee ◽  
Chang Choi ◽  
Jaihwan Kim ◽  
Sun Kim ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Receptor Antagonist ◽  
Analgesic Effect ◽  
Adrenergic Receptor ◽  
Mechanical Allodynia ◽  
Intraperitoneal Administration ◽  
Cold Allodynia ◽  
Oxaliplatin Treatment ◽  
Noradrenaline Reuptake ◽  
Adrenergic Antagonist

The analgesic effect of venlafaxine (VLX), which is a selective serotonin and noradrenaline reuptake inhibitor (SNRI), has been observed on oxaliplatin-induced neuropathic pain in mice. Significant allodynia was shown after oxaliplatin treatment (6 mg/kg, i.p.); acetone and von Frey hair tests were used to assess cold and mechanical allodynia, respectively. Intraperitoneal administration of VLX at 40 and 60 mg/kg, but not 10 mg/kg, significantly alleviated these allodynia. Noradrenaline depletion by pretreatment of N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 50 mg/kg, i.p.) blocked the relieving effect of VLX (40 mg/kg, i.p.) on cold and mechanical allodynia. However, serotonin depletion by three consecutive pretreatments of para-chlorophenylalanine (PCPA, 150 mg/kg/day, i.p.) only blocked the effect of VLX on mechanical allodynia. In cold allodynia, the α2-adrenergic antagonist idazoxan (10 μg, i.t.), but not the α1-adrenergic antagonist prazosin (10 μg, i.t.), abolished VLX-induced analgesia. Furthermore, idazoxan and 5-HT3 receptor antagonist bemesetron (MDL-72222, 15 μg, i.t.), but not prazosin or mixed 5-HT1, 2 receptor antagonist methysergide (10 μg, i.t.), abolished VLX-induced analgesia in mechanical allodynia. In conclusion, 40 mg/kg of VLX treatment has a potent relieving effect against oxaliplatin-induced neuropathic pain, and α2-adrenergic receptor, and both α2-adrenergic and 5-HT3 receptors are involved in this effect of VLX on cold and mechanical allodynia, respectively.

scholarly journals Spinal Cord Stimulation Attenuates Mechanical Allodynia and Increases Central Resolvin D1 Levels in Rats With Spared Nerve Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Xueshu Tao ◽  
Xin Luo ◽  
Tianhe Zhang ◽  
Brad Hershey ◽  
Rosana Esteller ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Spinal Cord Stimulation ◽  
Mechanical Allodynia ◽  
Male Rat ◽  
Dependent Manner ◽  
Spared Nerve Injury ◽  
Resolvin D1 ◽  
Cold Allodynia

Mounting evidence from animal models of inflammatory and neuropathic pain suggests that inflammation regulates the resolution of pain by producing specialized pro-resolving mediators (SPMs), such as resolvin D1 (RvD1). However, it remains unclear how SPMs are induced in the central nervous system and whether these mechanisms can be reconciled with outcomes of neuromodulation therapies for pain, such as spinal cord stimulation. Here, we show that in a male rat model of neuropathic pain produced by spared nerve injury (SNI), 1 kHz spinal cord stimulation (1 kHz SCS) alone was sufficient to reduce mechanical allodynia and increase RvD1 in the cerebrospinal fluid (CSF). SNI resulted in robust and persistent mechanical allodynia and cold allodynia. Spinal cord electrode implantation was conducted at the T11-T13 vertebral level 1 week after SNI. The spinal locations of the implanted electrodes were validated by X-Ray radiography. 1 kHz SCS was applied for 6 h at 0.1 ms pulse-width, and this stimulation alone was sufficient to effectively reduce nerve injury-induced mechanical allodynia during stimulation without affecting SNI-induced cold allodynia. SCS alone significantly reduced interleukin-1β levels in both serum and CSF samples. Strikingly, SCS significantly increased RvD1 levels in the CSF but not serum. Finally, intrathecal injection of RvD1 (100 and 500 ng, i.t.) 4 weeks after nerve injury reduced SNI-induced mechanical allodynia in a dose-dependent manner. Our findings suggest that 1 kHz SCS may alleviate neuropathic pain via reduction of IL-1β and via production and/or release of RvD1 to control SNI-induced neuroinflammation.

scholarly journals Methods for Evaluating Sensory, Affective and Cognitive Disorders in Neuropathic Rodents

2020 ◽  
Vol 18 ◽  
Author(s):  
Enza Palazzo ◽  
Ida Marabese ◽  
Francesca Gargano ◽  
Francesca Guida ◽  
Carmela Belardo ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Animal Models ◽  
Mechanical Allodynia ◽  
Scientific Community ◽  
Cognitive Disorders ◽  
Dependent Manner ◽  
Cold Allodynia ◽  
Time Points ◽  
Effective Drugs ◽  
Heat Hyperalgesia

: The animal models of neuropathic pain that faithfully reproduce the symptoms that occur in humans are a fundamental tool for understanding the mechanisms underlying the disease, identifying new targets, and developing effective drugs. So far, the studies aimed at describing the animal models of neuropathic pain have been focused mainly on the sensory symptoms associated with the disease consisting of mechanical allodynia and hyperalgesia, cold allodynia and hyperalgesia, and heat hyperalgesia. However, affective, and cognitive comorbidities occur in patients suffering from neuropathic pain, arising in a closely associated and dependent manner on the sensory symptoms. The same occurs in animal models of neuropathic pain in which anxiety- and depressive-like behaviors and cognitive disorders are observable at different time points from the induction of neuropathy. Today there are several tests available that exploit different paradigms in rodents for measuring sensorial, affective, and cognitive behavior. This review will describe those mainly used in the scientific community. The tests mainly used are based on the motor activity of the animals tested, so it is fundamental that it remains unaffected in the model used for inducing neuropathic pain. We hope that this review will be useful to the scientific community to direct the choice towards the best, most suitable, and simplest tests for the study of the sensory, affective, and cognitive symptoms associated with neuropathic pain.

scholarly journals Endothelin receptor type A is involved in the development of oxaliplatin-induced mechanical allodynia and cold allodynia acting through spinal and peripheral mechanisms in rats

2021 ◽  
Vol 17 ◽  
pp. 174480692110580
Author(s):  
Kae Matsuura ◽  
Atsushi Sakai ◽  
Yuji Watanabe ◽  
Yasunori Mikahara ◽  
Atsuhiro Sakamoto ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Receptor Antagonist ◽  
Mechanical Allodynia ◽  
Intraperitoneal Administration ◽  
Type A ◽  
Sprague Dawley ◽  
Cold Allodynia ◽  
Receptor Antagonism ◽  
Nociceptive Transmission ◽  
Peripheral Actions

Oxaliplatin, a platinum-based chemotherapeutic agent, frequently causes severe neuropathic pain typically encompassing cold allodynia and long-lasting mechanical allodynia. Endothelin has been shown to modulate nociceptive transmission in a variety of pain disorders. However, the action of endothelin varies greatly depending on many variables, including pain causes, receptor types (endothelin type A (ETA) and B (ETB) receptors) and organs (periphery and spinal cord). Therefore, in this study, we investigated the role of endothelin in a Sprague–Dawley rat model of oxaliplatin-induced neuropathic pain. Intraperitoneal administration of bosentan, a dual ETA/ETB receptor antagonist, effectively blocked the development or prevented the onset of both cold allodynia and mechanical allodynia. The preventive effects were exclusively mediated by ETA receptor antagonism. Intrathecal administration of an ETA receptor antagonist prevented development of long-lasting mechanical allodynia but not cold allodynia. In marked contrast, an intraplantar ETA receptor antagonist had a suppressive effect on cold allodynia but only had a partial and transient effect on mechanical allodynia. In conclusion, ETA receptor antagonism effectively prevented long-lasting mechanical allodynia through spinal and peripheral actions, while cold allodynia was prevented through peripheral actions.

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