• The Korean Journal of Pain
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• 제36권1호
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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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• 제8권1호
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• pp.18-24
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• 1995

We produced the causalgiform pain by the tight ligation of L5 and L6 spinal nerves in the adult rats. To evalute the effect of Ketamine -noncompetitive NMDA (N-methyl-D aspartate) antagoinst- on the causalgiform pain, we tested the changes of; withdrawal sensitivity to the innocuous mechanical stimulation of Von Frey hair 2.35 g(mechanical allodynia); withdrawal frequency to the cold stimulation of acetone (cold allodynia); and total withdrawal time (second) to the cold ($4^{\circ}C$) plate stimulation (cold hyperalgesia) after the administration of 1 mg, 3 mg, 10 mg/kg ketamine. The results were as follows: 1) Cold hyperalgesia was significantly reduced (p<0.05) by 1 mg, 3mg, 01 mg/kg ketamine. 2) Cold allodynia and mechanical allodynia was significantly reduced (p<0.05) by 10 mg/kg ketamine. Above results suggest a therapeutic utility of ketamine in treatment of causalgia - especially, cold hyperalgesia.

• Parasites, Hosts and Diseases
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• 제60권4호
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• pp.247-254
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• 2022

Vincristine (VCR) is a chemotherapeutic agent widely used in treatment of malignancies. However, VCR has a limitation in use since it commonly causes a painful neuropathy (VCR-induced peripheral neuropathy, VIPN). Inflammatory cytokines secreted by immune cells such as macrophages can exacerbate allodynia and hyperalgesia, because inhibiting the inflammatory response is a treatment target for VIPN. In this study, we investigated whether Trichinella spiralis, a widely studied helminth for its immunomodulatory abilities, can alleviate VCR-induced allodynia. Von Frey test showed that T. spiralis infection improved mechanical allodynia at 10 days after VCR injection. We further observed whether the difference was due to mitigated axon degeneration, but no significant difference between the groups in axonal degeneration in sciatic nerves and intra-epidermal nerve fibers was found. Conversely, we observed that number of infiltrated macrophages was decreased in the sciatic nerves of the T. spiralis infected mice. Moreover, treatment of T. spiralis excretory-secretory products caused peritoneal macrophages to secrete decreased level of IL-1β. This study suggests that T. spiralis can relieve VCR-induced mechanical allodynia by suppressing neuroinflammation and that application of controllable degree of helminth may prove beneficial for VIPN treatment.

• Journal of Korean Neurosurgical Society
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• 제52권1호
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• pp.32-36
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• 2012

Objective : Alcoholic neuropathy is characterized by allodynia (a discomfort evoked by normally innocuous stimuli), hyperalgesia (an exaggerated pain in response to painful stimuli) and spontaneous burning pain. The aim of the present study is to investigate the effect of rolipram, a phosphodiesterase 4 inhibitor, against alcohol-induced neuropathy in rats. Methods : Allodynia was induced by administering 35% v/v ethanol (10 g/kg; oral gavage) to Spraue-Dawley rats for 8 weeks. Rolipram and saline (vehicle) were administered intraperitoneally. Mechanical allodynia was measured by using von Frey filaments. Somatosensory evoked potential (SEP) was proposed as complementary measure to assess the integrity of nerve pathway. Results : The ethanol-induced mechanical allodynia began to manifest from 3 week, and then peaked within 1 week. Beginning from 3 week, latency significantly started to increased in control group. In rolipram treated rats, the shorter latency was sustained until 8 weeks (p<0.05). The mechanical allodynia, which began to manifest on the 3 weeks, intraperitoneal injections of rolipram sustained statistical difference until 8 weeks, the final week of the study (p<0.05). Conclusion : This study suggests that rolipram might alleviate mechanical allodynia induced by alcohol in rats, which clearly has clinical implication.

• International Journal of Oral Biology
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• 제40권3호
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• pp.117-125
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• 2015

The present study investigated the role of central $GABA_A$ and $GABA_B$ receptors in orofacial pain in rats. Experiments were conducted on Sprague-Dawley rats weighing between 230 and 280 g. Intracisternal catheterization was performed for intracisternal injection, under ketamine anesthesia. Complete Freund's Adjuvant (CFA)-induced thermal hyperalgesia and inferior alveolar nerve injury-induced mechanical allodynia were employed as orofacial pain models. Intracisternal administration of bicuculline, a $GABA_A$ receptor antagonist, produced mechanical allodynia in naive rats, but not thermal hyperalgesia. However, CGP35348, a $GABA_B$ receptor antagonist, did not show any pain behavior in naive rats. Intracisternal administration of muscimol, a $GABA_A$ receptor agonist, attenuated the thermal hyperalgesia and mechanical allodynia in rats with CFA treatment and inferior alveolar nerve injury, respectively. On the contrary, intracisternal administration of bicuculline also attenuated the mechanical allodynia in rats with inferior alveolar nerve injury. Intracisternal administration of baclofen, a $GABA_B$ receptor agonist, attenuated the thermal hyperalgesia and mechanical allodynia in rats with CFA treatment and inferior alveolar nerve injury, respectively. In contrast to $GABA_A$ receptor antagonist, intracisternal administration of CGP35348 did not affect either the thermal hyperalgesia or mechanical allodynia. Our current findings suggest that the $GABA_A$ receptor, but not the $GABA_B$ receptor, participates in pain processing under normal conditions. Intracisternal administration of $GABA_A$ receptor antagonist, but not $GABA_B$ receptor antagonist, produces paradoxical antinociception under pain conditions. These results suggest that central GABA has differential roles in the processing of orofacial pain, and the blockade of $GABA_A$ receptor provides new therapeutic targets for the treatment of chronic pain.

• Journal of Acupuncture Research
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• 제26권6호
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• pp.67-76
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• 2009

Objectives : The purpose of this study is to examine if Radix Aconiti herbal acupuncture may be effective to the neuropathic pain(mechanical allodynia, cold allodynia) in a rat model of neuropathic pain. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, L5 spinal nerve was ligated by 6-0 silk thread. After neurophathic surgery, the author examined if the animals exhibited the behavioral sign of allodynia. The allodynia was assessed by stimulating the medial malleolus with von frey filament and acetone. Three days after the neuropathic surgery, Radix Aconiti herbal acupuncture was injected at Hwando($GB_{30}$) one time per two days for 2 weeks. After that, the author examined the withdrawal response of neuropathic rats' legs by von frey filament and acetone stimulation. And also the author examined c-Fos in the midbrain central gray of neuropathic rats and the change of WBC, RBC, HGB, HCT count in the blood of neuropathic rats. Results : The Radix Aconiti herbal acupuncture injected Hwando($GB_{30}$) decreased the withdrawal response of mechanical allodynia that assessed with von frey filament in RA1-$GB_{30}$, RA2-$GB_{30}$ group as compared with control group. The Radix Aconiti herbal acupuncture injected Hwando($GB_{30}$) decreased the withdrawal response of chemical allodynia(cold allodynia) that assessed with acetone in RA1-$GB_{30}$, RA2-$GB_{30}$ group as compared with control group. The Radix Aconiti herbal acupuncture injected Hwando($GB_{30}$) showed the significant between control group and RA2-$GB_{30}$ group in the c-Fos expression. The Radix Aconiti herbal acupuncture injected Hwando($GB_{30}$) did not show the significant between control group and RA1-$GB_{30}$ group, RA2-$GB_{30}$ group and RA3-$GB_{30}$ group in the WBC, RBC, HGB, HCT count. Conclusions : We have noticed that Radix Aconiti herbal acupuncture at Hwando($GB_{30}$) decreased mechanical allodynia and cold allodynia in the model of neuropathic pain compared with the control group. C-fos expression in the central gray of that group was also decreased compared with the control group. This study can be used as a basic resource on a study and a treatment of pain.

• Journal of Acupuncture Research
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• 제21권1호
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• pp.240-251
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• 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.

• International Journal of Oral Biology
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• 제35권3호
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• pp.83-89
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• 2010

We investigated the role of the central MAPK pathways in extra-territorial (referred) pain resulting from inflammation of the temporomandibular joint (TMJ). Experiments were carried out on male Sprague-Dawley rats weighing 220-280 g. Under anesthesia, these animals were injected with $50\;{\mu}L$ of complete Freund's adjuvant (CFA) into the TMJ using a Hamilton syringe. In the control group, saline was injected into the TMJ. To identify the extent of inflammation of the TMJ, Evans blue dye (0.1%, 5 mg/kg) was injected intravenously at 1, 3, 6, 9, 12 and 15 days after CFA injection. The concentration of Evans blue dye in the extracted TMJ tissue was found to be significantly higher in the CFA-treated animals than in the saline-treated group. Air-puff thresholds in the vibrissa pad area were evaluated 3 days before and at 3, 6, 9, 12, 15 and 18 days after CFA injection into the TMJ. Referred mechanical allodynia was established at 3 days, remained until 12 days, and recovered to preoperative levels at 18 days after CFA injection. This referred mechanical allodynia was observed in contralateral side area. To investigate the role of central MAPK pathways, MAPK inhibitors ($10\;{\mu}g$) were administrated intracisternally 9 days after CFA injection. SB203580, a p38 MAPK inhibitor, significantly attenuated referred mechanical allodynia, as compared with the vehicle group. PD98059, a MEK inhibitor, also reduced CFA-induced referred mechanical allodynia. These results suggest that TMJ inflammation produces extra-territorial mechanical allodynia, and that this is mediated by central MAPK pathways.

• The Korean Journal of Pain
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• 제25권4호
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• pp.213-220
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• 2012

Background: It has been demonstrated that the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and apoptotic cell death in the dorsal root ganglion (DRG) following spinal nerve constriction injury play a role in the initiation and continuation of hyperalgesia and allodynia. The present study was designed to investigate the effects of ethyl pyruvate (EP) on mechanical and cold allodynia, TNF-${\alpha}$ expression, and apoptosis in DRG after spinal nerve ligation injury. Methods: Rats were divided into 3 groups: control, pre-EP, and post-EP. EP (50 mg/kg) was intraperitoneally injected 30 minutes before (pre-EP) or after (post-EP) surgery. Behavioral tests to determine mechanical and cold allodynia were conducted before surgery and 4 and 7 days after surgery. Seven days after surgery, TNF-${\alpha}$ protein levels in DRG were evaluated by enzyme-linked immunosorbent assay, and DRG apoptosis was determined by immunohistochemical detection of activated caspase-3. Results: Treatment with EP significantly reduced mechanical and cold allodynia following spinal nerve ligation injury. TNF-${\alpha}$ protein levels in the pre-EP ($4.7{\pm}1.2$ pg/200 ${\mu}g$; P < 0.001) and post-EP ($6.4{\pm}1.8$ pg/200 ${\mu}g$; P < 0.001) groups were 2-3 times lower than the control group ($14.4{\pm}1.2$ pg/200 ${\mu}g$). The percentages of neurons and satellite cells that co-localized with caspase-3 were also significantly lower in the pre-EP and post-EP groups than the control group. Conclusions: These results demonstrate that EP has a strong anti-allodynic effect that acts through the inhibition of TNF-${\alpha}$ expression and apoptosis in DRG after spinal nerve ligation injury.

• The Korean Journal of Physiology and Pharmacology
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• 제21권6호
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• pp.657-666
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• 2017

Paclitaxel, a chemotherapeutic drug, induces severe peripheral neuropathy. Gabapentin (GBT) is a first line agent used to treat neuropathic pain, and its effect is mediated by spinal noradrenergic and muscarinic cholinergic receptors. Electro-acupuncture (EA) is used for treating various types of pain via its action through spinal opioidergic and noradrenergic receptors. Here, we investigated whether combined treatment of these two agents could exert a synergistic effect on paclitaxel-induced cold and mechanical allodynia, which were assessed by the acetone drop test and von Frey filament assay, respectively. Significant signs of allodynia were observed after four paclitaxel injections (a cumulative dose of 8 mg/kg, i.p.). GBT (3, 30, and 100 mg/kg, i.p.) or EA (ST36, Zusanli) alone produced dose-dependent anti-allodynic effects. The medium and highest doses of GBT (30 and 100 mg/kg) provided a strong analgesic effect, but they induced motor dysfunction in Rota-rod tests. On the contrary, the lowest dose of GBT (3 mg/kg) did not induce motor weakness, but it provided a brief analgesic effect. The combination of the lowest dose of GBT and EA resulted in a greater and longer effect, without inducing motor dysfunction. This effect on mechanical allodynia was blocked by spinal opioidergic (naloxone, $20{\mu}g$), or noradrenergic (idazoxan, $10{\mu}g$) receptor antagonist, whereas on cold allodynia, only opioidergic receptor antagonist blocked the effect. In conclusion, the combination of the lowest dose of GBT and EA has a robust and enduring analgesic action against paclitaxel-induced neuropathic pain, and it should be considered as an alternative treatment method.