• Journal of Pharmacopuncture
• /
• v.17 no.1
• /
• 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.

• Biomolecules & Therapeutics
• /
• v.27 no.4
• /
• pp.414-422
• /
• 2019

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-$1{\beta}$ and tumor-necrosis factor-${\alpha}$ in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and $NF-{\kappa}B$ in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.

• The Korean Journal of Pain
• /
• v.33 no.3
• /
• pp.226-233
• /
• 2020

Background: We aimed to compare interlaminar epidural steroid injections (ILESI) and bilateral transforaminal epidural steroid injections (TFESI) on pain intensity, functional status, depression, walking distance, and the neuropathic component in patients with lumbar central spinal stenosis (LCSS). Methods: The patients were divided into either the ILESI or the bilateral TFESI groups. Prime outcome measures include the numerical rating scale (NRS), Oswestry disability index (ODI), Beck depression inventory (BDI), and pain-free walking distance. The douleur neuropathique en 4 questions score was used as a secondary outcome measure. Results: A total of 72 patients were finally included. NRS, ODI, and BDI scores showed a significant decline in both groups in all follow-ups. Third-month NRS scores were significantly lower in the ILESI group (P = 0.047). The percentages of decrease in the ODI and BDI scores between the baseline and the third week and third month were significantly higher in the ILESI group (P = 0.017, P = 0.001 and P = 0.048, P = 0.030, respectively). Pain-free walking distance percentages from the baseline to the third week and third month were significantly higher in the ILESI group (P = 0.036, P < 0.001). The proportion of patients with neuropathic pain in the bilateral TFESI group significantly decreased in the third week compared to the baseline (P = 0.020). Conclusions: Both ILESI and TFESI are reliable treatment options for LCSS. ILESI might be preferred because of easier application and more effectiveness. However, TFESI might be a better option in patients with more prominent neuropathic pain.

• The Korean Journal of Pain
• /
• v.11 no.2
• /
• pp.201-209
• /
• 1998

Background: Tricyclic antidepressants (TCA) have been used for various pain syndromes for their analgesic effects. They, however, often have anticholinergic side effects and therefore search for more selective drugs with fewer side effects is justified. Paroxetine, a selective serotonin reuptake inhibitor devoid of autonomic side effects, was evaluated for its role as an analgesic adjuvant in the management of neuropathic pain. Method: According to individual diagnostic group as diabetic neuropathy, postherpetic neuralgia, central pain syndrome and cancer related plexopathy, 10 patients per each group were equally accumulated. Patients have been stabilized in their analgesic regimen at least four weeks prior to enrollment into study. TCA, if taken, was discontinued for two weeks for wash out period. Baseline four point verbal pain intensity score was obtained and oral administration of paroxetine 20 mg was initiated. At two weeks follow-up visit, pain intensity scores, pain improvement scores judged by family, drug efficacy, tolerability and overall evaluation were assessed. The incidence of side effects were also obtained. Result: After two weeks of treatment, pain intensity scores decreased in 77.5% of patients and no patients experienced aggravation. These findings were objectively reflected in pain improvement scores judged by family members. But, the number of nonresponders was different among groups. In drug efficacy, tolerability and overall evaluation, the proportions of patients who scored as excellent or good were 75%, 80% and 80% respectively. Incidence of side effects was 27.5%, but the side effects spontaneously disappeared after discontinuation of medication. Conclusion: Paroxetine, a selective serotonin reuptake inhibitor, appears to be effective as adjuvant analgesic for the management of various neuropathic pain syndromes.

• Journal of Acupuncture Research
• /
• v.21 no.1
• /
• pp.240-251
• /
• 2004

Objective: We have studied to know effects of acupuncture at SI3, BL40, SI3 BL40 on mechnical allodynia, cold allodynia and c-fos protein expression in a model of neuropathic pain of rat. Methods: A model of neuropathic pain was made by injuring tibial nerve and sural nerve while common peroneal nerve was maintained. after 2 weeks, we performed behavioral tests for 7 days to try out mechnical allodynia using von frey filament and cold allodynia using acetone, which are calculated by counting withdrawal response on foot. Rat brains removed and sliced on 8th days. Serial sections were immunohistochemically reacted with polyclonal c-fos antibody. The numbers of c-Fos protein immunoreactive neurons in the central gray were examined using scion image program. Results: Mechanical allodynia in the SI3, BL40, SI3 BL40 groups were diminished compared with the control group. Cold allodynia in the SI3, BL40, SI3 BL40 groups were diminished compared with the control group. c-Fos protein expression on the central gray in the SI3 group were lower than that of the control group. Conclusions: We have noticed that acupuncture at SI3, BL40, SI3 BL40 diminished mechanical allodynia and cold allodynia in a model of neuropathic pain compared with the control group. c- Fos protein expression in the central gray of that group was also decreased compared with the control group. pain control using acupunture was accumulated as time goes by. This study can be used as a basic resource on a study and a treatment of pain.

• Journal of Hospice and Palliative Care
• /
• v.1 no.1
• /
• pp.65-68
• /
• 1998

The neuropathic pains are not well controlled by common analgesics and opioid drugs in terminal cancer patients. The types of these pains are divided within the two cages, one is due to continuous central sensitization and the other is due to paroxymal peripheral sensitization. The mechanism of continuous central sensitization is the activity of dorsal horn neurones that are activated by C-fiber input. The tricyclic antidepressants, non-tricyclic antidepressants, and oral local anaesthesia probably produce analgesic effects in neuropathic pains through suppression of this activity. The mechanism of paroxymal peripheral sensitization is the hyper-excitability of peripheral neurones. The neuropathic pains due to peripheral sensitization respond relatively the anticonvulsants and baclofen that stabilize membranes and suppress paroxymal electrical discharge. The patients was a 38-year-old female who complained of hyperthemia on upper right extremity. The symptom of this patient was improved with anticonvulsant(dilantin 600mg).

• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.2
• /
• pp.125-130
• /
• 2015

Cholecystokinin is known to be involved in the modulation of nociception and to reduce the efficacy of morphine analgesia. This study investigated the effects of intrathecal administration of morphine and the cholecystokinin type B antagonist CI-988 on below-level neuropathic pain after spinal cord injury in rats. We also examined the interaction of morphine and CI-988 in the antinociceptive effect. Both morphine and CI-988 given individually increased the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner. The combination of ineffective doses of intrathecally administered CI-988 and morphine produced significant analgesic effects and the combination of effective doses resulted in analgesic effects that were greater than the sum of the individual effects of each drug. Thus, morphine showed a synergistic interaction with CI-988 for analgesia of central neuropathic pain.

• Biomolecules & Therapeutics
• /
• v.24 no.5
• /
• 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.

• Journal of Yeungnam Medical Science
• /
• v.19 no.1
• /
• pp.49-54
• /
• 2002

The central pain in patient with spinal cord injury is a common and disabling sequela. The microsurgical DREZ(Dorsal Root Entry Zone)otomy is a surgical procedure effective in the treatment of intractable pain and spasticity in spinal cord injured patients. It consists of a microsurgical lesions performed in the ventrolateral region of the dorsal root entry zone at the selected levels. This report presents one case with incomplete paraplegia patient, who had chronic central neuropathic pain ineffective to many conservative treatments in bilateral T10 and right T11 segments and both lower extremities, is relieved from the pain after microsurgical DREZotomy. In conclusion, microsurgical DREZotomy is one method of effective treatments for spinal cord injured patients with intractable central neuropathic pain.

• Korean Journal of Acupuncture
• /
• v.38 no.3
• /
• pp.151-161
• /
• 2021

Objectives : The effects of a combined stimulation of 658 nm, 830 nm, 904 nm, and 1064 nm laser acupuncture treatment (LAT) and electroacupuncture treatment (EAT) on GB39 and GB34 on neuropathic pain in rats induced by tibial and sural nerve transection were studied in this paper. Methods : To express a neuropathic pain model, surgery was performed to transection rats' tibial and sural nerves. The rats were divided into normal group, control group, and experimental groups. In addition, the experimental groups were divided into 658 nm laser and electroacupuncture (LAT658+EAT), 830 nm laser and electroacupuncture (LAT830+EAT), 904 nm laser and electroacupuncture (LAT904+EAT), and 1064 nm laser and electroacupuncture (LAT830+EAT). For the treatment of the experimental groups, electroacupuncture and different laser wavelengths were alternately applied to GB34 and GB39 twice a week for 3 weeks for 1 minute 30 seconds. The withdrawal response of neuropathic rats' legs by acetone stimulation was observed, as well as the c-Fos in the central gray region in the midbrain of neuropathic rats together with Bax, Bcl2, and mGluR5 expressions associated with apoptosis. Results : Compared with the control group, a significant decrease in the frequency of paw withdrawal in response to acetone allodynia was observed in LAT658+EAT and LAT830+EAT groups in 6th times, LAT904+EAT group in 2^nd, 3^rd, and 6^th times, and LAT1064+EAT group in 2^nd and 6^th times, respectively. For c-fos positive cells in the central gray region, a significant decrease was observed in LAT830+EAT, LAT904+EAT, and LAT1064+EAT groups in comparison with the control group. In Bax expression, LAT1064+EAT group showed a significant decrease compared to the control group. In Bcl-2 expression, the LAT658+EAT,the LAT904+EAT, and the LAT1064+EAT groups increased significantly compared to the control group. LAT830+EAT, LAT904+EAT, and LAT1064+EAT groups showed significantly increased mGlu5 expression compared to the control group. Conclusions : The combination of laser for each wavelength and electroacupuncture alternately performed in this study is thought to be effective in improving neuropathic pain and apoptosis.