• Parasites, Hosts and Diseases
• /
• 제60권4호
• /
• pp.247-254
• /
• 2022

Vincristine (VCR) is a chemotherapeutic agent widely used in treatment of malignancies. However, VCR has a limitation in use since it commonly causes a painful neuropathy (VCR-induced peripheral neuropathy, VIPN). Inflammatory cytokines secreted by immune cells such as macrophages can exacerbate allodynia and hyperalgesia, because inhibiting the inflammatory response is a treatment target for VIPN. In this study, we investigated whether Trichinella spiralis, a widely studied helminth for its immunomodulatory abilities, can alleviate VCR-induced allodynia. Von Frey test showed that T. spiralis infection improved mechanical allodynia at 10 days after VCR injection. We further observed whether the difference was due to mitigated axon degeneration, but no significant difference between the groups in axonal degeneration in sciatic nerves and intra-epidermal nerve fibers was found. Conversely, we observed that number of infiltrated macrophages was decreased in the sciatic nerves of the T. spiralis infected mice. Moreover, treatment of T. spiralis excretory-secretory products caused peritoneal macrophages to secrete decreased level of IL-1β. This study suggests that T. spiralis can relieve VCR-induced mechanical allodynia by suppressing neuroinflammation and that application of controllable degree of helminth may prove beneficial for VIPN treatment.

• 대한약침학회지
• /
• 제17권1호
• /
• pp.74-79
• /
• 2014

Objectives: This study was conducted to clarify the analgesic effect of toad cake and toad-cake-containing herbal drugs. Methods: We counted the writhing response of mice after the intraperitoneal administration of acetic acid as a nociceptive pain model and the withdrawal response after the plantar surface stimulation of the hind paw induced by partial sciatic nerve ligation of the mice as a neuropathic pain model to investigate the analgesic effect of toad cake and toad-cake-containing herbal drugs. A co-treatment study with serotonin biosynthesis inhibitory drug 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA), the catecholamine biosynthesis inhibitory drug ${\alpha}$-methyl-DL-tyrosine methyl ester hydrochloride (AMPT) or the opioid receptor antagonist naloxone hydrochloride was also conducted. Results: Analgesic effects in a mouse model of nociceptive pain and neuropathic pain were shown by oral administration of toad cake and toad-cake-containing herbal drugs. The effects of toad cake and toad-cake-containing herbal drugs disappeared upon co-treatment with PCPA, but not with AMPT or naloxone in the nociceptive pain model; the analgesic effect of toad-cake-containing herbal drugs also disappeared upon co-treatment with PCPA in the neuropathic pain model. Conclusion: Toad cake and toad-cake-containing herbal drugs have potential for the treatments of nociceptive pain and of neuropathic pain, such as post-herpetic neuralgia, trigeminal neuralgia, diabetic neuralgia, and postoperative or posttraumatic pain, by activation of the central serotonin nervous system.

• The Korean Journal of Pain
• /
• 제35권2호
• /
• pp.173-182
• /
• 2022

Background: Neurokinin-1 (NK1) and calcitonin gene-related peptide (CGRP) play a vital role in pain pathogenesis, and these proteins' antagonists have attracted attention as promising pharmaceutical candidates. The authors investigated the anti-nociceptive effect of co-administration of the CGRP antagonist and an NK1 antagonist on pain models compared to conventional single regimens. Methods: C57Bl/6J mice underwent sciatic nerve ligation for the neuropathic pain model and were injected with 4% formalin into the hind paw for the inflammatory pain model. Each model was divided into four groups: vehicle, NK1 antagonist, CGRP antagonist, and combination treatment groups. The NK1 antagonist aprepitant (BIBN4096, 1 mg/kg) or the CGRP antagonist olcegepant (MK-0869, 10 mg/kg) was injected intraperitoneally. Mechanical allodynia, thermal hypersensitivity, and anxiety-related behaviors were assessed using the von Frey, hot plate, and elevated plus-maze tests. The flinching and licking responses were also evaluated after formalin injection. Results: Co-administration of aprepitant and olcegepant more significantly alleviated pain behaviors than administration of single agents or vehicle, increasing the mechanical threshold and improving the response latency. Anxiety-related behaviors were also markedly improved after dual treatment compared with either naive mice or the neuropathic pain model in the dual treatment group. Flinching frequency and licking response after formalin injection decreased significantly in the dual treatment group. Isobolographic analysis showed a meaningful additive effect between the two compounds. Conclusions: A combination pharmacological therapy comprised of multiple neuropeptide antagonists could be a more effective therapeutic strategy for alleviating neuropathic or inflammatory pain.

• Clinical Pain
• /
• 제19권1호
• /
• pp.49-53
• /
• 2020

Piriformis muscle syndrome is a condition that causes direct muscle pain around piriformis muscle or sciatica from irritated sciatic nerve and the diagnosis remains debatable. The main treatment is symptomatic relief from conservative therapy such as medication and piriformis stretching exercise, and various therapeutic injections including local anesthetic, corticosteroid, botulinum toxin can be considered for diagnostic and therapeutic purposes. In this case, a 54-year-old male who had sciatica and gait disturbance showed piriformis muscle hypertrophy in the pelvis MRI. From imaging studies, electrodiagnostic study and physical examination, he was diagnosed with piriformis muscle syndrome. He underwent trigger point injection and botulinum toxin injection into the piriformis muscle, and pain and gait disturbance significantly improved. This case reports a case of piriformis muscle syndrome with clinical symptom of gait disturbance, which was improved by botulinum toxin injection.

• Biomolecules & Therapeutics
• /
• 제30권4호
• /
• pp.328-333
• /
• 2022

Repeated morphine administration induces tolerance to its analgesic effects. A previous study reported that repeated morphine treatment activates transient receptor potential vanilloid type 1 (TRPV1) expression in the sciatic nerve, dorsal root ganglion, and spinal cord, contributing to morphine tolerance. In the present study, we analyzed TRPV1 expression and binding sites in supraspinal pain pathways in morphine-tolerant mice. The TRPV1 mRNA levels and binding sites were remarkably increased in the cortex and thalamus of these animals. Our data provide additional insights into the effects of morphine on TRPV1 in the brain and suggest that changes in the expression of, and binding to TRPV1 in the brain are involved in morphine tolerance.

• Biomolecules & Therapeutics
• /
• 제24권5호
• /
• pp.489-494
• /
• 2016

Neuropathic pain (NPP) is the main culprit among chronic pains affecting the normal life of patients. Procaine is a frequently-used local anesthesia with multiple efficacies in various diseases. However, its role in modulating NPP has not been reported yet. This study aims at uncovering the role of procaine in NPP. Rats were pretreated with procaine by intrathecal injection. Then NPP rat model was induced by sciatic nerve chronic compression injury (CCI) and behavior tests were performed to analyze the pain behaviors upon mechanical, thermal and cold stimulations. Spinal expression of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was detected by qRT-PCR and western blot. JAK2 was also overexpressed in procaine treated model rats for behavior tests. Results showed that procaine pretreatment improved the pain behaviors of model rats upon mechanical, thermal and cold stimulations, with the best effect occurring on the $15^{th}$ day post model construction (p<0.05). Procaine also inhibited JAK2 and STAT3 expression in both mRNA (p<0.05) and protein levels. Overexpression of JAK2 increased STAT3 level and reversed the improvement effects of procaine in pain behaviors (p<0.01). These findings indicate that procaine is capable of attenuating NPP, suggesting procaine is a potential therapeutic strategy for treating NPP. Its role may be associated with the inhibition on JAK2/STAT3 signaling.

• 동의생리병리학회지
• /
• 제26권4호
• /
• pp.462-468
• /
• 2012

The present study was conducted with the object of examining how ST36 and LR3 electro acupuncture affects the injured side and the intact side in rats with sciatic nerve injury. For this study, we divided rats into a control group that were injured but not treated, experimental group I that were injured and had electro acupuncture on the intact side, experimental group II that were injured and had electro-acupuncture on the injured side, and experimental group III that were injured and had electro-acupuncture on both the intact side and the injured side, and performed behavioral and immunohistochemical tests. The results of this study are as follows. In the results of hot plate test, on Day 1 of experiment, experimental group I did not show a statistically significant difference but experimental group II and III showed a statistically significant difference, and on Day 2 and 3, all of experimental group I, II and III showed a statistically significant difference. In the results of SFI test, on Day 7 of experiment, experimental group I did not show a statistically significant difference but experimental group II and III showed a statistically significant difference, and on Day 14 and 21, all of experimental group I, II and III showed a statistically significant difference. In the results of immunohistochemical test, the expression of c-fos decreased gradually on Day 1, 2 and 3 in all the experimental groups, and the decrease was larger in the experimental groups that had electro-acupuncture than in the control group. In the results of immunohistochemical test, the expression of BDNF increased gradually on Day 7, 14 and 21 in all the experimental groups, and the expression was higher in the experimental groups than in the control group. Summing up the results, ST36 and LR3 electro acupuncture was effective when it was applied to the injured side and to both sides after sciatic nerve injury, but it was also effective in pain relief and nerve regeneration when it was applied to the intact side.

• 동의생리병리학회지
• /
• 제23권4호
• /
• pp.895-897
• /
• 2009

Lonicera japonica has been widely used for chronic inflammatory diseases in many Asian countries. Its analgesic effect has not been explored yet. This study aimed to test the analgesic potential of methanol extracts from Lonicera japonica (MELJ) in rat neuropathic mctel. Neuropathic pain was pacts ed by partial sciatic nerve injury. Two weeks after surgery, neuropathic rats received oral administration of MELJ at doses of either 0.0 g/kg, 0.2 g/kg or 0.4 g/kg. At dose of 0.0 g, rats were administered with saline only and used as conracl. The behavioral tests for f 0.0 g, raand ccld hs were adma were weformed up to 2 hours after treatment. The MELJ at the dose 0.4 g/kg dmg gfg, ntly alleviated f 0.0 g, rahyperalgesia, but not cold hyperalgesia. These results showed that the MELJ had, although transient, analgesic effect on mechanical hyperalgesia in the rat neuropathic model.

• The Korean Journal of Pain
• /
• 제12권1호
• /
• pp.8-15
• /
• 1999

Following peripheral nerve injury, rats will show a tactile allodynia and hyperalgesia. But the mechanism of allodynia is still obscure. The present studies, using rats rendered allodynia by loosely constrictive ligation of the common sciatic nerve (Bennett Model) and tight ligation of L5 & L6 spinal nerve (Chung Model), aimed to investigate the changes of metabotrophic glutamate receptor type 5 on the development of tactile allodynia. Male Sprague-Dawley rats (130~200 g) were anesthetized with halothane, the rats were randomly divided into one of these three groups, Group 1 (Sham operation), Group 2 (Bennett model) and Group 3 (Chung model). Seven days after surgical procedure, the animal was reanesthetized and decapitated. The spinal cord was quickly removed and stored at deep freezer for polymerase chain reaction (RT-PCR). In Group 2&3, rats showed that tactile allodynia checked by up-down method with calibrated 8 von Frey hair. The level of gene expression of mGluR5 mRNA was significantly increased in group 2 and 3. These increases was significantly different from sham operation, group 1. It was also showed that the increasing patterns of group 2 and 3 in the gene expression were similar correlation with the results of the threshold for tactile allodynia on von Frey hair test. Even though there were some differences between Bennett model and Chung model, these results suggested that mGluR5 had partly attributed to making a tactile allodynia from these models.

• The Korean Journal of Pain
• /
• 제28권2호
• /
• pp.96-104
• /
• 2015

Background: The present experiment was conducted to identify the cooperative effect of serine histogranin (SHG) and noradrenaline in alleviating peripheral neuropathic pain. Methods: Chronic constriction injury of the right sciatic nerve was used to induce chronic neuropathic pain. For drug delivery, a PE10 tube was inserted into the subarachnoid space. Acetone drops and a $44^{\circ}C$ water bath were used to evaluate the cold and heat allodynia, respectively. Placing and grasping reflexes were used to assess the locomotor system. Results: SHG at 0.5 and $1{\mu}g$significantly (P < 0.05) decreased the thermal allodynia. The cold allodynia was also significantly reduced by intrathecal injections of 0.5 (P < 0.05) and $1{\mu}g$(P < 0.001) of SHG. $1{\mu}g$of noradrenaline, but not $0.5{\mu}g$, significantly alleviated the cold (P < 0.01) and thermal (P < 0.05) allodynia. The ameliorating effect of noradrenaline or SHG disappeared when the two compounds were administrated in equal concentrations. A significant difference (P < 0.01 in the acetone and P < 0.05 in the heat) was observed in the groups under equal doses of the two compounds, with a lower effectiveness of the combination therapy. Conclusions: Our findings suggest that the simultaneous administrations of noradrenaline and SHG do not result in synergistic analgesia, and combination therapy may not be a good approach to the treatment of chronic neuropathic pain syndrome.