• The Korean Journal of Pain
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• v.27 no.3
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• pp.246-252
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• 2014

Background: Neuropathic pain is generally defined as a chronic pain state resulting from peripheral and/or central nerve injury. There is a lack of effective treatment for neuropathic pain, which may possibly be related to poor understanding of pathological mechanisms at the molecular level. Curcumin, a therapeutic herbal extract, has shown to be effectively capable of reducing chronic pain induced by peripheral administration of inflammatory agents such as formalin. In this study, we aimed to show the effect of curcumin on pain behavior and serum COX-2 level in a Chronic Constriction Injury (CCI) model of neuropathic pain. Methods: Wistar male rats (150-200 g, n = 8) were divided into three groups: CCI vehicle-treated, sham-operated, and CCI drug-treated group. Curcumin (12.5, 25, 50 mg/kg, IP) was injected 24 h before surgery and continued daily for 7 days post-surgery. Behavioral tests were performed once before and following the days 1, 3, 5, 7 after surgery. The serum COX-2 level was measured on day 7 after the surgery. Results: Curcumin (50 mg/kg) decreased mechanical and cold allodynia (P < 0.001) and produced a decline in serum COX-2 level (P < 0.001). Conclusions: A considerable decline in pain behavior and serum COX-2 levels was seen in rat following administration of curcumin in CCI model of neuropathic pain. High concentration of Curcumin was able to reduce the chronic neuropathic pain induced by CCI model and the serum level of COX-2.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.489-494
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• 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.

• The Korean Journal of Pain
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• v.25 no.1
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• pp.7-15
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• 2012

Background: Neuropathic pain is a chronic pain due to disorder in the peripheral or central nervous system with different pathophysiological mechanisms. Current treatments are not effective. Analgesic drugs combined can reduce pain intensity and side effects. Here, we studied the analgesic effect of nimesulide, nefopam, and morphine with different mechanisms of action alone and in combination with other drugs in chronic constriction injury (CCI) model of neuropathic pain. Methods: Male Wistar rats (n = 8) weighing 150-200 g were divided into 3 different groups: 1- Saline-treated CCI group, 2- Saline-treated sham group, and 3- Drug-treated CCI groups. Nimesulide (1.25, 2.5, and 5 mg/kg), nefopam (10, 20, and 30 mg/kg), and morphine (1, 3, and 5 mg/kg) were injected 30 minutes before surgery and continued daily to day 14 post-ligation. In the combination strategy, a nonanalgesic dose of drugs was used in combination such as nefopam + morphine, nefopam + nimesulide, and nimesulide + morphine. Von Frey filaments for mechanical allodynia and acetone test for cold allodynia were, respectively, used as pain behavioral tests. Experiments were performed on day 0 (before surgery) and days 1, 3, 5, 7,10, and 14 post injury. Results: Nefopam (30 mg/kg) and nimesulide (5 mg/kg) blocked mechanical and thermal allodynia; the analgesic effects of morphine (5 mg/kg) lasted for 7 days. Allodynia was completely inhibited in combination with nonanalgesic doses of nefopam (10 mg/kg), nimesulide (1.25 mg/kg), and morphine (3 mg/kg). Conclusions: It seems that analgesic drugs used in combination, could effectively reduce pain behavior with reduced adverse effects.

• The Korean Journal of Pain
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• v.35 no.3
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• pp.271-279
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• 2022

Background: Inflammation is known to underlie the pathogenesis in neuropathic pain. This study investigated the anti-inflammatory and neuroprotective mechanisms involved in antinociceptive effects of co-administration of acetaminophen and L-carnosine in chronic constriction injury (CCI)-induced peripheral neuropathy in male Wistar rats. Methods: Fifty-six male Wistar rats were randomly divided into seven experimental groups (n = 8) treated with normal saline/acetaminophen/acetaminophen + L-carnosine. CCI was used to induce neuropathic pain in rats. Hyperalgesia and allodynia were assessed using hotplate and von Frey tests, respectively. Investigation of spinal proinflammatory cytokines and antioxidant system were carried out after twenty-one days of treatment. Results: The results showed that the co-administration of acetaminophen and L-carnosine significantly (P < 0.001) increased the paw withdrawal threshold to thermal and mechanical stimuli in ligated rats compared to the ligated naïve group. There was a significant (P < 0.001) decrease in the levels of nuclear factor kappa light chain enhancer B cell inhibitor, calcium ion, interleukin-1-beta, and tumour necrotic factor-alpha in the spinal cord of the group coadministered with acetaminophen and L-carnosine compared to the ligated control group. Co-administration with acetaminophen and L-carnosine increased the antioxidant enzymatic activities and reduced the lipid peroxidation in the spinal cord. Conclusions: Co-administration of acetaminophen and L-carnosine has anti-inflammatory effects as a mechanism that mediate its antinociceptive effects in CCI-induced peripheral neuropathy in Wistar rat.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.153-160
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• 2017

In this study, we aim to determine the in vivo effect of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) on neuropathic pain, using three, principal peripheral neuropathic pain models. Four weeks after hUCB-MSC transplantation, we observed significant antinociceptive effect in hUCB-MSC-transplanted rats compared to that in the vehicle-treated control. Spinal cord cells positive for c-fos, CGRP, p-ERK, p-p 38, MMP-9 and MMP 2 were significantly decreased in only CCI model of hUCB-MSCs-grafted rats, while spinal cord cells positive for CGRP, p-ERK and MMP-2 significantly decreased in SNL model of hUCB-MSCs-grafted rats and spinal cord cells positive for CGRP and MMP-2 significantly decreased in SNI model of hUCB-MSCs-grafted rats, compared to the control 4 weeks or 8weeks after transplantation (p<0.05). However, cells positive for TIMP-2, an endogenous tissue inhibitor of MMP-2, were significantly increased in SNL and SNI models of hUCB-MSCs-grafted rats. Taken together, subcutaneous injection of hUCB-MSCs may have an antinociceptive effect via modulation of pain signaling during pain signal processing within the nervous system, especially for CCI model. Thus, subcutaneous administration of hUCB-MSCs might be beneficial for improving those patients suffering from neuropathic pain by decreasing neuropathic pain activation factors, while increasing neuropathic pain inhibition factor.