• The Korean Journal of Pain
• /
• v.29 no.3
• /
• pp.158-163
• /
• 2016

Background: Phenol and alcohol have been used to ablate nerves to treat pain but are not specific for nerves and can damage surrounding soft tissue. Lidocaine at concentrations > 8% injected intrathecal in the animal model has been shown to be neurotoxic. Tests the hypothesis that 10% lidocaine is neurolytic after a peri-neural blockade in an ex vivo experiment on the canine sciatic nerve. Methods: Under ultrasound, one canine sciatic nerve was injected peri-neurally with 10 cc saline and another with 10 cc of 10% lidocaine. After 20 minutes, the sciatic nerve was dissected with gross inspection. A 3 cm segment was excised and preserved in 10% buffered formalin fixative solution. Both samples underwent progressive dehydration and infusion of paraffin after which they were placed on paraffin blocks. The sections were cut at $4{\mu}m$ and stained with hemoxylin and eosin. Microscopic review was performed by a pathologist from Henry Ford Hospital who was blinded to which experimental group each sample was in. Results: The lidocaine injected nerve demonstrated loss of gross architecture on visual inspection while the saline injected nerve did not. No gross changes were seen in the surrounding soft tissue seen in either group. The lidocaine injected sample showed basophilic degeneration with marked cytoplasmic vacuolation in the nerve fibers with separation of individual fibers and endoneurial edema. The saline injected sample showed normal neural tissue. Conclusions: Ten percent lidocaine causes rapid neurolytic changes with ultrasound guided peri-neural injection. The study was limited by only a single nerve being tested with acute exposure.

• The Journal of Korean Medicine
• /
• v.24 no.3
• /
• pp.108-117
• /
• 2003

Objective : The central opioid mechanism of acupuncture analgesia has been fairly well documented in acute behavioral experiments, but little electrophysiological study has been performed on the peripheral mechanism and subtypes of opioid receptors responsible for acupuncture-induced antinociception in chronic animal models. In the present electrophysiological experiment, we studied the peripheral mechanism and opioid receptor subtypes which Were implicated in electroacupuncture-induced antinociception in the rat with chronic inflammatory and neurogenic pain. Methods : In the rat with complete Freund's adjuvant-induced inflammation and spinal nerve injury, dorsal horn cell responses to afferent C fiber stimulation were recorded before and after electroacupuncture (EA) stimulation applied to the contralateral Zusanli point for 30 minutes. Also studied Were the effects of specific opioid receptor antagonists and naloxone methiodide, which can not cross the blood-brain barrier, on EA-induced inhibitory action. Results : EA-induced inhibitory action was significantly attenuated by naloxone methiodide, suggesting that EA-induced inhibition was mediated through peripheral mechanism. Pretreatment, but not posttreatment of naltrexone and spinal application significantly blocked EA-induced inhibitory actions. In inflammatory and neurogenic pain models, ${\mu}-$ and ${\delta}-opioid$ receptor antagonists (${\beta}-funaltrexamine$ & naltrindole) significantly reduced EA-induced inhibitory action, but ${\kappa}-opioid$ receptor antagonist had weak inhibitory effect on EA-induced antinociception. Conclusion : These results suggest that 2Hz EA-stimulation induced antinoeiceptive action is mediated through peripheral as well as central mechanism, and mainly through ${\mu}-$ and ${\delta}-opioid$ receptors.

• The Korean Journal of Physiology
• /
• v.26 no.2
• /
• pp.143-150
• /
• 1992

The purpose of this study is to obtain the effective concentration of capsaicin to relieve pain with no change in the number of C-fibers and its effective duration for pain relief. Capsaicin has been used extremely as a experimental tool and as topical medications for acute or chronic tissue injuries and partial nerve injury is the main cause of causalgiform pain disorders in humans. Here, the left sciatic nerve was ligated unilaterally at the high level of the thigh to prepare an animal model of this pain condition. The rat developed guarding behavior of the ipsilateral hind paw within a few hours after the operation and this behavior was maintained for several months thereafter, suggesting the possibility of spontaneous pain. These animals were divided into two groups(4-week & 8-week) and each group was subdivided into five groups by different concentration (0.05, 0.1, 0.5, 1.0 & 2.0%). Each capsaicin concentration was treated locally on the spinal cord-side of the ligated nerve and the foot withdrawal latency was measured. Thereafter, the dorsal roots of L5 were removed from both sides immediately after in tracardial perfusion for the counting of C-fibers by the histological procedure. There were no significant differences in the foot-withdrawal latency and the number of C-fibers between the left side treated with 0.05% capsaicin and the right side treated with the vehicle. However, latencies of the left sides treated with 0.1, 0.5, and 1.0% capsaicin increased significantly throughout 4-6 weeks with almost no change in the number of C-fibers, and the latencies showed the trends to approach slowly to those of the conditions after operation. The latency of subgroup treated with 2.0% increased by approximate 10% more than that of the right side throughout 8 weeks, and the number of C-fibers decreased by about 30% or more These results suggest that the elevated latency with capsaicin(0.1-1.0%) treatment is due to the inhibition of impulse transmission throughout the primary afferent fiber and the data from 2.0% are due to partial destruction of C-fibers. Therefore, capsaicin concentrations from 0.1% to 1.0% are probably very effective for the treatment of causalgiform pain with almost no destruction of C-fibers.

• The Korean Journal of Pain
• /
• v.34 no.3
• /
• pp.250-261
• /
• 2021

Background: Complex regional pain syndrome type I (CRPS-I) consists of disorders caused by spontaneous pain or induced by some stimulus. The objective was to verify the effects of photobiomodulation (PBM) using 830 nm wavelength light at the affected paw and involved spinal cord segments during the warm or acute phase. Methods: Fifty-six mice were randomized into seven groups. Group (G) 1 was the placebo group; G2 and G3 were treated with PBM on the paw in the warm and acute phase, respectively; G4 and G5 treated with PBM on involved spinal cord segments in the warm and acute phase, respectively; G6 and G7 treated with PBM on paw and involved spinal cord segments in the warm and acute phase, respectively. Edema degree, thermal and mechanical hyperalgesia, skin temperature, and functional quality of gait (Sciatic Static Index [SSI] and Sciatic Functional Index [SFI]) were evaluated. Results: Edema was lower in G3 and G7, and these were the only groups to return to baseline values at the end of treatment. For thermal hyperalgesia only G3 and G5 returned to baseline values. Regarding mechanical hyperalgesia, the groups did not show significant differences. Thermography showed increased temperature in all groups on the seventh day. In SSI and SFI assessment, G3 and G7 showed lower values when compared to G1, respectively. Conclusions: PBM irradiation in the acute phase and in the affected paw showed better results in reducing edema, thermal and mechanical hyperalgesia, and in improving gait quality, demonstrating efficacy in treatment of CRPS-I symptoms.

• The Korean Journal of Physiology and Pharmacology
• /
• v.11 no.4
• /
• pp.149-154
• /
• 2007

Kainic acid (KA) causes neurodegeneration, but no consensus has been reached concerning its mechanism. Nitric oxide may be a regulator of the mechanism. We identified differentially expressed genes in the hippocampus of mice treated with kainic acid, together with or without L-NAME, a nonselective nitric oxide synthase inhibitor, using a new differential display PCR method based on annealing control primers. Eight genes were identified, including clathrin light polypeptide, TATA element modulatory factor 1, neurexin III, ND4, ATPase, $H^+$ transporting, V1 subunit E isoform 1, and N-myc downstream regulated gene 2. Although the functions of these genes and their products remain to be determined, their identification provides insight into the molecular mechanism(s) involved in KA-induced neuronal cell death in the hippocampal CA3 area.

• International Journal of Oral Biology
• /
• v.34 no.3
• /
• pp.157-164
• /
• 2009

We recently described a novel animal model of trigeminal neuropathic pain following compression of the trigeminal ganglion (Ahn et al., 2009). In our present study, we adapted this model using male Sprague-Dawley rats weighing between 250-260 g and then analyzed the behavioral responses of these animals following modified chronic compression of the trigeminal ganglion. Under anesthesia, the rats were mounted onto a stereotaxic frame and a 4% agar solution ($10{\mu}L$) was injected in each case on the dorsal surface of the trigeminal ganglion to achieve compression without causing injury. In the control group, the rats received a sham operation without agar injection. Air-puff, acetone, and heat tests were performed at 3 days before and at 3, 7, 10, 14, 17, 21, 24, 30, 40, 55, and 70 days after surgery. Compression of the trigeminal ganglion produced nociceptive behavior in the trigeminal territory. Mechanical allodynia was established within 3 days and recovered to preoperative levels at approximately 60 days following compression. Mechanical hyperalgesia was also observed at 7 days after compression and persisted until the postoperative day 40. Cold hypersensitivity was established within 3 days after compression and lasted beyond postoperative day 55. In contrast, compression of the trigeminal ganglion did not produce any significant thermal hypersensitivity when compared with the sham operated group. These findings suggest that compression of the trigeminal ganglion without any injury produces prolonged nociceptive behavior and that our rat model is a useful system for further analysis of trigeminal neuralgia.

• Journal of the Korea Academia-Industrial cooperation Society
• /
• v.15 no.8
• /
• pp.5088-5094
• /
• 2014

Hovenia dulcis extract (HDE) has positive effects on alcohol degradation, recovery of liver damage and antioxidant activities. This study examined whether HDE exerts an ameliorative effect on inflammatory orifacial pain in an animal algesic model with formalin. The animals (rats) were divided into four groups: group I (control), group II (right facial subcutaneous injection of 5% formalin, inflammatory orifacial pain group), group III (5% formalin + distilled water administration), and group IV injection (5% formalin + 4.5 ml/kg of HDE), respectively. The scores from the scratch and effleurage tests were applied to evaluate the differences between three groups. The expression of p38 MAPK, iNOS and Nrf2 in the brain and medulla oblongata, which are involved in pain regulation, inflammation, antioxidation and nitric oxide production, were analyzed by western blot. The degree of orifacial pain was significantly lower in group IV than in groups I, II and, III. The expression of p38MAPK, iNOS and Nrf2 in the brain and medulla were also lower in group IV than in the other groups. These findings suggested that a Hovenia dulcis extract can attenuate inflammatory orifacial pain by suppressing the expression of p38 MAPK, iNOS and Nrf2.

• Archives of Pharmacal Research
• /
• v.26 no.3
• /
• pp.232-236
• /
• 2003

Elsholtzia splendens Nakai has been used in North-East Asia as an ingredient of folk medicines for treating cough, headache and inflammation. The present investigation was carried out to establish its in vivo anti-inflammatory activity using several animal models of inflammation and pain. The 75% ethanol extract of the aerial part of E. splendens significantly inhibited mouse croton oil-induced, as well as arachidonic acid-induced, ear edema by oral administration (44.6% inhibition of croton oil-induced edema at 400 mg/kg). This plant material also showed significant inhibitory activity against the mouse ear edema induced by multiple treatment of phorbol ester for 3 days, which is an animal model of subchronic inflammation. In addition, E. splendens exhibited significant analgesic activity against mouse acetic acid-induced writhing (50% inhibition at 400 mg/kg), while indomethacin (5 mg/kg) demonstrated 95% inhibition. E. splendens ($5-100{\;}{\mu}g/mL$) significantly inhibited $PGE_2$ production by pre-induced cyclooxygenase-2 of lipopolysaccharide-treated RAW 264.7 cells, suggesting that cyclooxygenase-2 inhibition might be one of the cellular mechanisms of anti-inflammation.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.35 no.1
• /
• pp.1-7
• /
• 2021

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting side effects of neurotoxic chemotherapeutic agents that lead to decreased quality of life and dose reduction, delay or even cessation of treatment. The purpose of this systematic review is to evaluate the effect and the underlying mechanisms of bee venom (BV) pharmacopuncture therapy for CIPN in animal models. We searched for the available experimental literature using BV for CIPN through the Pubmed databases. Ten experimental studies were finally included in this review. In the oxaliplatin or paclitaxel-induced CIPN animal model, BV significantly relieved pain caused both mechanical and cold stimulation. It was suggested that the effect of BV is mediated by the stimulation effect of spinal α1- and α2-adrenergic receptors as a potential mechanism. In the future, more experimental studies are needed.

• Journal of Korean Medicine Rehabilitation
• /
• v.30 no.1
• /
• pp.79-93
• /
• 2020

Objectives While sciatic neuropathy is one of the common symptoms which have the lifetime incidence of 13~40%, still there is no consensus about the standardized and the most effective conservative treatment. In addition, the importance of systematic review and meta-analysis of preclinical are growing as they could suggest possible effective treatment strategy for future studies. Therefore, we conducted systematic review and meta-analysis to estimate analgesic effect of acupuncture on sciatica in rat models. Methods Systematic search was conducted for all controlled comparative preclinical trials which assessed analgesic effect of acupuncture in sciatica rat models. Database of PubMed, EMBASE, Web of Science, CNKI and 6 Korean databases were used. The primary outcome was pain, which is evaluated by stimulus behavior tests in rat models. We assessed the methodological quality with Systematic Review Centre for Laboratory Animal Experimentation's risk of bias tool. RevMan 5.3 was used for meta-analysis and subgroup analysis was conducted according to treatment site, acupuncture point, treatment period and frequency used in electroacupuncture. Results 14 studies were finally included following our inclusion criteria. The data from meta-analysis indicated that the acupuncture significantly improved the result values of behavior tests for pain evaluation, compared to no-treatment control group in animal models (standardized mean difference=4.43, 95% confidence interval 3.16 to 5.69, Z=6.84, p<0.00001; χ²=68.02, p<0.00001; I²=82%). The results of subgroup analysis indicate that acupuncture treatment of unilateral site, distal acupoints, longer treatment period and applying 2/100 Hz frequency in electroacupuncture could be more effective. Conclusions Systematic review and meta-analysis of animal studies are getting important for the future clinical studies and the improvement of heatlh care. Therefore the results of the study would provide evidence and better design for the forthcoming studies.