• 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.

• The Journal of Korean Physical Therapy
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• v.22 no.3
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• pp.99-105
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• 2010

Purpose: The purpose of this study was to evaluate the development of pain behavior and the expression of CCL2/CCR2 and CX3CL1/CX3CR1 at above and below the level of hemisection of the spinal cord in a rat model. Methods: Spinal cords of adult female Sprague-Dawley rats (n= 16, 200~250 g, 6~8 weeks old) were hemisected at T13 on the right side to develop the spinal hemisection injury model. We compared behavioral responses of the hemisection and of a sham surgery group. Behavioral tests for motor function (by the BBB locomotor scale), and for pain response for mechanical and cold allodynia were assessed postoperatively (PO) for 21 days. Expression of mRNA for chemokines and their receptors (CCL2/CCR2 and CX3CL1/CX3CR1) below and above the level of the spinal cord dissection were examined by RT-PCR. Results: We observed gradual motor improvement and the development of mechanical and cold allodynia on the ipsilateral hindpaw after spinal hemisection injury. We also found upregulation of mRNA expression of CCL2/CCR2 both above and below the level of spinal cord dissection but CX3CL1/CX3CR1 mRNA expression. Conclusion: Upregulation of CCL2/CCR2 is associated with neuropathic pain after spinal hemisection injury. CCL2/CCR2 may play an important role in the development of neuropathic pain after SCI as well as of peripheral neuropathic pain. These findings may improve understanding of the pathophysiological mechanism of neuropathic pain after SCI.

• The Journal of Korean Physical Therapy
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• v.22 no.3
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• pp.71-77
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• 2010

Purpose: To determine whether upregulation of inducible nitric oxide synthase (iNOS) transcription and translation is related to radicular pain in a model of lumbar disc herniation. Also, to investigate the temporal changes of mRNA expression of iNOS and the identity of iNOS and transient receptor potential vanilloid (TRPV) 1 channel expression cells in dorsal root ganglion (DRG) of a model of lumbar disc herniation. Methods: A lumbar disc herniated rat model was developed by implantation of the autologous nucleus pulposus, harvested from the coccygeal vertebra of each tail, on the left L5 nerve root just proximal to the DRG. Rats were tested for mechanical allodynia of the plantar surface of both hind paws 2 days before surgery and 1, 5, 10, 20 and 30 days postoperatively. Reverse transcription polymerase chain reaction (RT-PCR) was used to follow iNOS mRNA expression. To stain iNOS and TRPV1 in DRG, an immunohistochemical study was done 10 days after surgery. Results: A significant drop in mechanical withdrawal threshold on the ipsilateral and contralateral hind paws was observed 1 day after surgery and was prolonged to 30 days in rats with lumbar disc herniation. The expression of mRNA for iNOS peaked at postoperative day 10 on both sides of the DRG. iNOS-positive sensory neurons in the DRG varied in size from large to small diameter cells. A majority of small and intermediate sensory neurons were TRPV1-positive cells. Double immunofluorescence staining for TRPV1 and iNOS revealed that most intermediate TRPV1-positive sensory neurons co-localized with iNOS-positive neurons. Conclusion: Nucleus pulposus-induced mechanical allodynia can be generated without mechanical compression. This pain is related to temporal changes in expression of iNOS mRNA in the DRG. Co-localization of TRPV1 and iNOS in intermediate neurons of the DRG is correlated with pain modality and intensity.

• The Korean Journal of Pain
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• v.24 no.4
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• pp.191-198
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• 2011

Background: Postlaminectomy peridural fibrosis is inevitable. Some studies have compared and identified the effects of high molecular weight hyaluronic acids (HMWHA) and low molecular weight hyaluronic acids (LMWHA) on peridural fibrosis in postlaminectomy animal models. However, no studies have been found that compare pain behaviors between hyaluronic acids or among hyaluronic acids and other solid materials. The purpose of this study was to examine the correlation between pain-related behaviors and histopathologic changes in laminectomized rats using various peridurally administered materials. Methods: Forty male Sprague-Dawley rats, laminectomized at the L5 and L6 levels, were divided into four groups: group C, laminectomy only; group L, laminectomy and LMWHA application; group H, laminectomy and HMWHA application; group F, laminectomy and fat interposition. Pain behaviors were checked before, 3 days, 1 week, and 3 weeks after surgery. Histopathological changes were checked at the L5 level 3 weeks after the surgery. Results: The 50% withdrawal thresholds in groups L and H were higher than that in groups C and F three days after laminectomy (P < 0.05). The paw withdrawal time did not change among the groups and in each group during the study period. Peridural fibrosis in group F was significantly lower than in the other groups (P < 0.05). Conclusions: Hyaluronic acids significantly reduced mechanical allodynia but not thermal hyperalgesia. Peridural fibrosis did not show any correlation with pain behaviors. There have been limited studies on the correlation between peridural fibrosis and pain behavioral change, which should be verified by further studies.

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

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.2
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• pp.97-105
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• 2022

Background: The pentadecapeptide BPC-157 has been shown to have anti-inflammatory and wound healing effects on multiple target tissues and organs. Peptides have potent anti-inflammatory effects on periodontal tissues in rats with periodontitis. Few studies have investigated the effect of BPC-157 on pain after dental procedures or oral surgeries. The purpose of the present study was to investigate the antinociceptive effects of BPC-157 on postoperative incisional pain in rats. Methods: Sprague-Dawley rats were randomly divided into five groups: control (saline with the same volume), BPC10 (10 ㎍/kg of BPC-157), BPC20 (20 ㎍/kg of BPC-157), BPC40 (40 ㎍/kg of BPC-157), and morphine (5 mg/kg of morphine). A 1-cm longitudinal incision was made through the skin, fascia, and muscle of the plantar aspect of the hind paw in isoflurane-anesthetised rats. Withdrawal responses were measured using von Frey filaments at 0, 2, 6 h and 4, 7 d after incision. The formalin test was also performed to differentiate its anti-nociceptive effect from an inflammatory reaction or central sensitization. Pain behavior was quantified periodically in phases 1 and 2 by counting the number of flinches in the ipsilateral paw after injection with 30 µL of 5% formalin. Results: The threshold of mechanical allodynia was significantly increased in the BPC10, BPC20, BPC40 and morphine groups compared with that in the control group at 2 h. These increasing thresholds then returned to the levels of the control group. The BPC-157 group showed a much higher threshold at 4 days after incision than the control group. The thresholds of the BPC groups, except the morphine group, were normalized 7 days after incision. The flinching numbers of the BPC10, BPC20, BPC40 and morphine groups were significantly decreased in phase 1, but there was no decrease in the BPC-157 groups except the morphine group in phase 2. Conclusions: BPC-157 was effective only for a short period after incision. It was also effective during phase 1 but not during phase 2, as determined by the formalin test. BPC-157 might have a short antinociceptive effect, even though it has anti-inflammatory and wound healing effects.

• The Korean Journal of Pain
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• v.4 no.2
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• pp.186-190
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• 1991

Causalgia is an extremely incapacitating disease often associated with a major peripheral nerve injury, which is characterized by sustained diffuse burning pain, allodynia and hyperpathia. The condition follows traumatic nerve lesions, often combined with vasomotor and sudomotor disturbances and later trophic changes. While sympathectomy has been the classical treatment of causalgia, others nonsurgical therapies such as regional sympathetic block, IV regional sympathetic block, oral adrenolytic drugs, transcutaneous electrical nerve simulation, physical theraphy, cryotheraphy and psychotheraphy have been used. Causalgia is rare in children and early treatment is controversial because of the possibility of many different complications following aggressive treatment. This is a report of a 6-year-old girl with causalgia suffered after a right posterior tibial nerve injury following an intragluteal injection of an antipyretics. We successfully treated this syndrome with continuous epidural block using 0.5% lidocaine and no specific complication was encountered.

• The Journal of Internal Korean Medicine
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• v.21 no.5
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• pp.765-771
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• 2000

Objectives : To evaluate the pain control effect of combination treatment of Oriental Medicine on patients who suffered from thalamic pain syndrome caused by thalamic stroke. Methods : We reviewed the medical records and brain imaging data of all patients with thalamic stroke from September 1998 to August 2000 who visited to Department of Oriental Internal Medicine, National Medical Center. We evaluated clinical features of thalamic pain syndrome, including incidence, onset interval from stroke, nature, pain distribution, and assessed the pain control effect of combination treatment by Visual Analog Scale(VAS). Results : 64 cases were selected under the inclusion criteria, and 17 patients(26.5%) with thalamic pain syndrome were identified from 64 thalamic strokes. VAS proved combination treatment effective to control pain of thalamic pain syndrome. In 12 cases(70.5%), pain onset was within the first week poststroke. The patients with allodynia were 6(35.3%). In 12 cases(70.5%), the lesion was mainly located in the posterolateral areas of thalamus. Conclusion : We conclude that combination treatment of the Oriental Medicine modalities have pain control effectiveness on thalamic pain syndrome.(t=-5.47, p=0.0001)

• Journal of Korean Neurosurgical Society
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• v.39 no.1
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• pp.52-57
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• 2006

Objective : It has been suggested that the occurrence of persistent pain signal during the early postnatal period may alter an individual's response to pain later in life. The aim of this study is to assess whether neonatal nerve injury resulted in long-lasting consequences on nociceptive system in the rat. Methods : We examined whether neuropathic pain behaviors and the changes of spinal neuropeptides [SP, CGRP, VIP and VIP] induced by peripheral nerve injury within 1 day after birth [Neonate group] were different from those at 8 weeks after birth [Mature group]. Results : The Neonate group showed more robust and long-lasting pain behaviors than the Mature group. Immunohistochemical findings demonstrated that spinal SP- & CGRP-immunoreactivities[ir] of the ipsilateral to the contralateral side increased in the Neonate group, whereas those decreased in the Mature group. In addition, increase in spinal VIP- & NPY-ir of the ipsilateral to the contralateral side was more robust in the Mature group than in the Neonate group. Conclusion : These results suggest that peripheral nerve injury in the early postnatal period may result in long-lasting and potentially detrimental alterations in nociceptive pathways.

• Physical Therapy Korea
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• v.5 no.2
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• pp.106-117
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• 1998

The pain is common among individuals with physical disabilities. It can interfere with therapy since patients with pain can become uncooperative and reluctant to move. This paper reviews the natural physiological mechanisms that can reduce pain perception, and considers physiological mechanisms which contribute to clinical pain by describing how the pain system changes its sensitivity depending upon the body's needs. The peripheral and central mechanisms contributing to sensitised nociceptive system are described with reference to the symptoms of clinical pain such as hyperalgesia, allodynia sopntaneous 'on-going'-projected and referred pain. It is suggested that in some chronic pain the nociceptive system maintains a state of sensitivity despite the absence of on-going tissue damage and under such circumstances the nociceptive system itself may have become dysfunctional. Such situations are often initiated by damage to nervous tissue which results in changes in the activity and organization of neuronal circuits within the central nervous system. The ability of the nociceptive system to operate in a suppressed state is also discussed with reference to pain modulation. The physical therapist can help facilitate the activation of these mechanisms through a combination of noninvasive modalities, functional activities, and the therapeutic use of self.