• Journal of Pharmacopuncture
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• v.7 no.1 s.12
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• pp.53-61
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• 2004

Substantial evidence suggests that behavioral and reinforcing effects of cocaine can be mediated by the mesolimbic dopaminergic system. It has been shown that repeated injections of cocaine produce increase in locomotor activity, expression of the immediate-early gene, c-fos in the nucleus accumbens (NAc), which was one of the main dopaminergic terminal areas. Herbal-acupuncture as a therapeutic intervention has been widely used for the treatment of many functional disorders such as drug abuse. Coptidis Rhizoma (CR) and its main component, berberine (BER) were selected as herbal medicine of herbal-acupuncture. Both medicines have been known to have the therapeutic effect on the central nervous system. In order to investigate the effects of CR and BER herbalacupuncture at shenmen (HT7) point (CR/H and BER/H) on the cocaine-induced behavioral sensitization, the influence of CR/H and BER/H on repeated cocaine-induced locomotor activity, the change of c-Fos expression in the brain by immunohistochemistry were examined. Male SD rats were given CR/H (0.4mg/kg) and BER/H (0.1mg/kg) 30 min before daily injections of cocaine hydrochloride (15mg/kg. i.p.) 10 days. After 3 days withdrawal, rats received a challenge injection of cocaine (15mg/kg, i.p.). Systemic challenge with cocaine produced much larger increased locomotor activity, accumbal Fos-like immunoreactivity in the NAc. Pretreatment with CR/H and BER/H significantly inhibited cocaine-induced locomotor activity, the change of c-Fos expression in the rats. Our data demonstrated that the inhibitory effects of cocaine-induced behavioral sensitization by CR/H and BER/H were closely associated with the reduction of presynaptic dopamine release in the NAc. These results suggest that CR/H and BER/H can be effectively applied to cocaine addiction.

• The Korean Journal of Pain
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• v.35 no.3
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• pp.240-249
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• 2022

Background: Widespread pain partially depends upon sensitization of central pain mechanisms. However, mechanisms controlling pain distribution are not completely known. The present study sought to assess skin temperature variations in the area of experimentally-induced pain and potential sex differences. Methods: Pressure-pain thresholds (PPTs) were measured on the right infraspinatus muscle. At the end of Day 0, all participants performed an eccentric exercise of the shoulder external rotators to induce muscle soreness 24 hours after. On Day 1, participants indicated on a body chart the area of pain induced by 60 seconds of suprathreshold pressure stimulation (STPS; PPT + 20%) on the right infraspinatus muscle. Skin temperature variations in the area of referred pain were recorded with an infrared thermography camera, immediately before and after the STPS. Results: Twenty healthy, pain-free individuals (10 females) participated. On Day 0, the pre-STPS temperature was higher than the post-STPS temperature on the arm (P = 0.001) and forearm (P = 0.003). On Day 1, the pre-STPS temperature was higher than the post-STPS temperature on the shoulder (P = 0.015), arm (P = 0.001), and forearm (P = 0.010). On Day 0, the temperature decrease after STPS in females was greater than in males on the forearm (P = 0.039). On Day 1, a greater temperature decrease was found amongst females compared with males at the shoulder (P = 0.018), arm (P = 0.046), and forearm (P = 0.005). Conclusions: These findings indicate that sympathetic vasomotor responses contribute to expand pressure-induced referred pain, especially among females.

• The Korean Journal of Pain
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• v.35 no.2
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• pp.152-159
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• 2022

Background: Subjects with frozen shoulder (FS) might not be comfortable with vigorous physical therapy. Clinical trials assessing the effect of graded motor imagery (GMI) in FS are lacking. The aim of this study was to determine the effect of GMI as an adjunct to conventional physiotherapy in individuals with painful FS. Methods: Twenty subjects aged 40-65 years having stage I and II of FS were randomly divided into two study groups. The conventional physiotherapy group (n = 10) received electrotherapy and exercises while the GMI group (n = 10) received GMI along with the conventional physiotherapy thrice a week for 3 weeks. Pre- (Session 1) and post- (Session 9) intervention analysis for flexion, abduction, and external rotation range of motion (ROM) using a universal goniometer, fear of movement using the fear avoidance belief questionnaire (FABQ), pain with the visual analogue scale, and functional disability using the shoulder pain and disability index (SPADI) was done by a blinded assessor. Results: Statistically significant difference was seen within both the groups for all the outcomes. In terms of increasing abduction ROM as well as reducing fear of movement, pain, and functional disability, the GMI group was significantly better than control group. However, both groups were equally effective for improving flexion and external rotation ROM. Conclusions: Addition of GMI to the conventional physiotherapy proved to be superior to conventional physiotherapy alone in terms of reducing pain, kinesiophobia, and improving shoulder function for stage I and II of FS.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.767-773
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• 2004

Substantial evidence suggests that repeated injections of nicotine produce increase in locomotor activity and expression of the immediate-early gene, c-fos in the dopaminergic target areas. Herbal medicine as a therapeutic intervention has been widely used for the treatment of mental dysfunction. Many studies have shown that Cortex Phellodendris (CP) can affect the biochemical balance in the central nervous system. In order to investigate whether CP have an influence on their nicotine-induced behavioral sensitization, we examined the effect of CP on nicotine-induced locomotor activity and c-Fos expression in the striatum and nucleus accumbens utilizing the Fos-like immunohistochemistry (FLI). Male SD rats received CP (200㎎/㎏, i.p.) 30 min before repeated daily injections of nicotine (0.4㎎/㎏, s.c.) for 7 days. Rats were followed withdrawal for 3 days and one challenge for 1 day. System challenge with nicotine produced a much larger increase in locomotor activity and accumbal FLI. Pretreatment with CP significanly inhibited nicotine-induced locomotor activity and FLI in the striuatum and nucleus accumbens. These results demonstrated that reduction in locomotor activity by CP may be reflected by reduction of dopamine release and postsynaptic neuronal activity in the striatum and nucleus accumbens. Our results suggest that CP may have therapeutic effect on nicotine addiction. Supported by a fund (99-PJ9-PG1-002-0004).

• The Korean Journal of Pain
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• v.36 no.1
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• pp.137-246
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• 2023

Background: To investigate the relationship between cutaneous allodynia (CA) and kinesiophobia, gastrointestinal system (GIS) symptom severity, physical activity, and disability, and to determine whether CA, pain, and disability were influencing factors for kinesiophobia, GIS symptoms, and physical activity in individuals with migraine. Methods: The study included 144 individuals with migraine. CA, kinesiophobia, GIS symptoms, physical activity level, and migraine-related disability were evaluated with the Allodynia Symptom Checklist, the Tampa Kinesiophobia Scale (TKS), the Gastrointestinal Symptom Rating Scale (GSRS), the International Physical Activity Questionnaire-7, and the Migraine Disability Assessment Scale (MIDAS), respectively. Results: The CA severity was only associated with TKS (r = 0.515; P < 0.001), GSRS-total (r = 0.336; P < 0.001), GSRS-abdominal pain (r = 0.323; P < 0.001), GSRS-indigestion (r = 0.257; P = 0.002), GSRS-constipation (r = 0.371; P < 0.001), and MIDAS scores (r = 0.178; P = 0.033). Attack frequency (P = 0.015), attack duration (P = 0.035) and presence of CA (P < 0.001) were risk factors for kinesiophobia. Attack frequency (P = 0.027) and presence of CA (P = 0.004) were risk factors for GIS symptoms. Conclusions: There was a relationship between the CA and kinesiophobia, GIS symptoms, and disability. CA and attack frequency were found to be risk factors for kinesiophobia and GIS symptoms. Migraine patients with CA should be assessed in terms of kinesiophobia, GIS, and disability. Lifestyle changes such as exercise and dietary changes and/or pharmacological treatment options for CA may increase success in migraine management.

• The Korean Journal of Pain
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• v.12 no.1
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• pp.21-26
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• 1999

Background: Preoperative blocking of surgical nociceptive inputs may prevent sensitization of central nervous system (CNS) and reduce postoperative pain. The stress responses to surgical trauma consist of increase in catabolic hormones and decrease in anabolic hormones. We studied whether preoperative low dose epidural bupivacaine and morphine could affect postoperative pain, changes plasma cortisol, and serum glucose. Methods: Thirty patients undergoing total abdominal hysterectomy were randomly assigned to one of three groups. General anesthesia was induced in all patients and after that, epidural blocks were done except the control group (n=10) patients. Preoperative block group (n=10) received 0.5% bupivacaine 50 mg and morphine 2 mg epidurally as a bolus before operation and followed by 0.1% bupivacaine $5\;mghr^{-1}$ and morphine $0.2\;mghr^{-1}$ for 10 hours. Postoperative block group (n=10) received the same doses of bupivacaine and morphine under the same method postoperatively. Postoperative pain relief was provided with i.v. fentanyl through Patient-Controlled-Analgesia Pump. Postoperative pain by visual analogue scores (VAS), analgesic requirement (first requirement time, total amounts used), side effects, plasma cortisol level and serum glucose level were compared. Results: Until postoperative 6 hrs, VAS of control group was higher than those of the epidural groups. No difference was observed in VAS between the two epidural groups. First analgesics requirement time and total amounts of used analgesics were not different between the two epidural groups, but first analgesic requirement time of preoperative block group was significantly prolonged compared with control group. Plasma cortisol and serum glucose levels were not different among groups. Conclusions: Low dose preoperative epidural bupivacaine and morphine could not reduce postoperative pain, plasma cortisol level and serum glucose level compared with postoperative block group.

• Physical Therapy Rehabilitation Science
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• v.8 no.1
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• pp.15-21
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• 2019

Objective: The purpose of this study was to identify whether cutaneous sensory (CS) changes induced by mechanical intervention (MI) increases the trigger point threshold of the same spinal segment as well as to investigate the relationship between the amounts of change in CS pressure pain thresholds (PPT). Design: Randomized controlled trial. Methods: Thirty-nine persons with myofacial pain (MFP) were recruited in this experiment. The subjects consisted of 20 men and 19 women (age 20-39). MI was applied on the subjects using the Graston technique for 5 minutes to induce CS changes. The CS changes were measured with sensory tests by using the Von Frey Filament, and PPT changes were estimated by using the pressure threshold meter. For the observation of sensory and PPT changes with time, the test was conducted for 15 minutes including a pre, post, and after intervention session. Results: CS threshold increased significantly when MI was applied (p<0.001). On the same spinal segment, changes in the right infraspinatus PPT was observed (p<0.001) but the PPT changes in other muscles were not significantly different. Furthermore, the control group CS and PPT were not significantly different. In addition, regression analysis showed that the CS changes have a larger impact on PPT in the same spinal segment (p<0.001). Conclusions: CS changes induced by MI make to change PPT on the same spinal segment. In other words, it is possible to identify PPT changes following CS changes except for the muscle which belongs to a different spinal segment. Therefore, application of MI is necessary for the CS changes in the same spinal segment. Furthermore, it can be useful in the clinical fields as a method of providing pain control and increasing the PPT.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.39-48
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• 2023

Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Storeoperated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic plasticity. However, the underlying mechanism of SOCE in mediating neuronal transmitter release and synaptic transmission remains ambiguous in neuropathic pain. Neuropathic rats were operated by spinal nerve ligations. Neurotransmissions were assessed by whole-cell recording in substantia gelatinosa. Immunofluorescence staining of STIM1 with neuronal and glial biomarkers in the spinal dorsal horn. The endoplasmic reticulum stress level was estimated from qRT-PCR. Intrathecal injection of SOCE antagonist SKF96365 dose-dependently alleviated mechanical allodynia in ipsilateral hind paws of neuropathic rats with ED₅₀ of 18 ㎍. Immunofluorescence staining demonstrated that STIM1 was specifically and significantly expressed in neurons but not astrocytes and microglia in the spinal dorsal horn. Bath application of SKF96365 inhibited enhanced miniature excitatory postsynaptic currents in a dosage-dependent manner without affecting miniature inhibitory postsynaptic currents. Mal-adaption of SOCE was commonly related to endoplasmic reticulum (ER) stress in the central nervous system. SKF96365 markedly suppressed ER stress levels by alleviating mRNA expression of C/ EBP homologous protein and heat shock protein 70 in neuropathic rats. Our findings suggested that nerve injury might promote SOCE-mediated calcium levels, resulting in long-term imbalance of spinal synaptic transmission and behavioral sensitization, SKF96365 produces antinociception by alleviating glutamatergic transmission and ER stress. This work demonstrated the involvement of SOCE in neuropathic pain, implying that SOCE might be a potential target for pain management.

• The Korean Journal of Pain
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• v.36 no.1
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• pp.51-59
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• 2023

Background: This study investigated the effect of an excess and a deficit of spinal 5-hydroxytryptamine (5-HT) on the mechanical allodynia and neuroglia activation in a rodent pain model of carrageenan inflammation. Methods: Male Sprague-Dawley rats were implanted with an intrathecal (i.t.) catheter to administer the drug. To induce an excess or deficit of 5-HT in the spinal cord, animals were given either three i.t. 5-HT injections at 24-hour intervals or a single i.t. injection of 5,7-dihydroxytryptamine (5,7-DHT) before carrageenan inflammation. Mechanical allodynia was measured using the von Frey test for 0-4 hours (early phase) and 24-28 hours (late phase) after carrageenan injection. The changes in the activation of microglia and astrocyte were examined using immunofluorescence of the dorsal horn of the lumbar spinal cord. Results: Both an excess and a deficit of spinal 5-HT had no or a minimal effect on the intensity of mechanical allodynia during the early phase but prevented the attenuation of mechanical allodynia during the late phase, which was observed in animals not treated with i.t. 5-HT or 5,7-DHT. Animals with an excess or deficit of 5-HT showed stronger activation of microglia, but not astrocyte, during the early and late phases, than did normal animals. Conclusions: Imbalance in the descending 5-HT pathway in the spinal cord could aggravate the mechanical allodynia and enhance the activation of microglia, suggesting that the spinal 5-HT pathway plays an essential role in maintaining the nociceptive processing in balance between facilitation and inhibition in inflammatory pain caused by carrageenan inflammation.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.164-174
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• 2000

Background: After an injury to tissue such as the skin, hyperalgesia develops. Hyperalgesia is characterized by an increase in the magnitude of pain evoked by noxious stimuli. It has been postulated that in the mechanism of hyperalgesia (especially secondary hyperalgesia) and allodynia, a sensitization of central nervous system such as spinal dorsal horn may contribute to development of hyperalgesia. However, the precise mechanism is still unclear. In the present study, we investigated the roles of N-methyl-D-aspartate (NMDA) receptor and nitric oxide (NO) system in the mechanism of hyperalgesia, and their relations with c-fos expression Methods: Inflammation was induced by injection of complete Freund adjuvant (CFA) into unilateral hindpaw of Sprague-Dawley rat. Behavioral studies measuring paw withdrawal responses by von Frey filaments and paw withdrawal latencies by radiant heat stimuli and stainings of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and c-fos immunoreactivity were performed. The effects of MK-801, an NMDA receptor blocker and $N^\omega$-nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor were evaluated. Results: 1) Injection of CFA induced mechanical allodynia, mechanical hyperalgesia and thermal hyperalgesia. And it increased the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 2) MK-801 inhibited mechanical hyperalgesia and thermal hyperalgesia induced by CFA and reduced the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 3) L-NNA inhibited the thermal hyperalgesia and reduced the number of NADPH-diaphorase positive neurons, but did not affect the number of c-fos expression neurons. Conclusions: These results suggest that in the mechanism of mechanical hyperalgesia, NMDA receptor but not NO-system is involved and in the case of thermal hyperalgesia both NMDA receptor and NO system are involved. NO system did not affect the expression of c-fos, but c-fos expression and NOS activity were dependent on the activity of NMDA receptor.