• Journal of Acupuncture Research
• /
• v.21 no.3
• /
• pp.133-144
• /
• 2004

Background and Objective : Twirling is one of the needling methods, which is frequently used for acupuncture in oriental medicine. Some thesis about needle manipulation has been reported that needle manipulation is more effective than plain acupuncture. So we have developed the auto-controlled twirling needle(ACTN) system which is most simple style of needle manipulation. The present study was conducted to see if ACTN can enhance the antinociceptive effect of acupuncture. Methods : To investigate the analgesic effect of acupuncture we used two pain model. One is acute pain model using tail flick latency(TFL), the other is neuropathic pain model using mechanical allodynia. For TFL test, rats were lightly anesthetized with pentobarbital sodium(40 mg/kg, i.p). To produce mechanical allodynia in the rat tail, the right superior caudal trunk was resected between the S1 and S2 spinal nerves. For plain acupuncture(PA), a needle was inserted into a Zusanli(ST36) for 15min. In combining ACTN with PA, twirling needle was performed once in a second. We measured the difference of analgesic effect of only PA and ACTN on two different kinds of pain. Results and conclusion : ACTN increased TFL more than PA. (15min P<0.001, 25min P<0.01). And ACTN also reduced neuropathic pain (15min P<0.01, 25min<0.05). But PA alone can't reduce the neuropathic pain. These results indicate that ACRN had more analgesic effect than PA. The mechanism that play a key role, and the condition which produce best analgesic effect of ACTN are to be studied further.

• Journal of Korean Medicine Rehabilitation
• /
• v.19 no.3
• /
• pp.15-32
• /
• 2009

Objectives : The purpose of this Study was to identify the effect of Dokhwalgisaeng-tang(Duhuoqisheng-tang) and Jungsongouhyul pharmacopuncture on pain control and nerve regeneration after crush injury in rat sciatic nerve. Methods : Neuropathic pain was induced by crush-induced model of right sciatic nerve. Animal groups were divided as follows; Group I: no treatment control group, Group II : experimental group treated with Dokhwalgisaeng-tang(Duhuoqisheng-tang), Group III : experimental group treated with Jungsongouhyul pharmacopuncture, and Group IV : experimental group treated with Dokhwalgisaeng-tang(Duhuoqisheng-tang) and Jungsongouhyul pharmacopuncture. To evaluate pain intensity, each group was observed paw withdrawal threshold and immunoreactivity on the c-fos before and after respective treatments in five hours, first, third, and fifth day. To evaluate nerve regeneration, those were observed SFI(Sciatic Functional Index) and GAP-43(Growth Associated Protein 43) after each treatment in seventh and thirteenth day. Results : 1. Paw withdrawal threshold to the mechanical stimuli made the significant difference between group IV and the control group after five days of the experiment. 2. Paw withdrawal threshold to the thermal stimuli made the significant difference between group I and III, I and IV, II and IV. 3. In immunohistochemical response of c-fos, as time passes, the immunoreactivity of all groups was decreased gradually. Especially, group IV was observed the lowest after three days. 4. The differences of sciatic function indexes in each group were significantly between group I and III, I and IV, II and IV after 14 days, and between group I and III, I and IV, II and IV, III and IV after 21 days. 5. In immunohistochemical response of GAP-43, all groups had higher GAP-43 immunoreactivity at the 14 days from post-injury and group IV showed highest immunoreactivity. Conclusions : Based on above the results, it is proposed that Dokhwalgisaeng-tang(Duhuoqisheng-tang) and Jungsongouhyul pharmacopuncture may be helpful as a treatment in neuropathic pain and nerve regeneration in rat model.

• The Korean Journal of Physiology and Pharmacology
• /
• v.25 no.5
• /
• pp.489-494
• /
• 2021

Oxaliplatin, a third-generation platinum derivative, is the mainstay of current antineoplastic medications for advanced colorectal cancer therapy. However, peripheral neuropathic complications, especially cold allodynia, undermine the life-prolonging outcome of this anti-cancer agent. Rosavin, a phenylpropanoid derived originally from Rhodiola rosea, exhibits a wide range of therapeutic properties. The present study explored whether and how rosavin alleviates oxaliplatin-induced cold hypersensitivity in mice. In the acetone drop test, cold allodynia behavior was observed from days 3 to 5 after a single injection of oxaliplatin (6 mg/kg, i.p.). Cold allodynia was significantly attenuated following rosavin treatment (10 mg/kg, i.p.). Specific endogenous 5-HT depletion by three consecutive pretreatments with parachlorophenylalanine (150 mg/kg/day, i.p.) abolished the analgesic action of rosavin; this effect was not observed following pretreatment with naloxone (opioid receptor antagonist, 10 mg/kg, i.p.). Furthermore, 5-HT_1A receptor antagonist WAY-100635 (0.16 mg/kg, i.p.), but not 5-HT₃ receptor antagonist MDL-72222 (1 mg/kg, i.p.), blocked rosavin-induced analgesia. These results suggest that rosavin may provide a novel approach to alleviate oxaliplatin-induced cold allodynia by recruiting the activity of 5-HT_1A receptors.

• Journal of the Korea Academia-Industrial cooperation Society
• /
• v.17 no.2
• /
• pp.123-128
• /
• 2016

The study was conducted to confirm the analgesic effects of the Carbenoxolone(CBX)and P2X receptor antagonist(iso-PPADS), which separates the gap junction in the facial neuropathic pain model. The experiment used white male Sprague-Dawley rats (240~280g). The second left molars on the lower jaw was extracted to induce facial neuropathic pain, and small dental implants were implanted to induce damage to the inferior alveolar nerve. When CBX was injected twice daily to the abdominal cavity, a significant analgesic effect at 5ug/kg was observed(p<0.05). In addition, when iso-PPADS was injected twice daily into the abdominal cavity, a significant analgesic reaction was observed at $25{\mu}g/kg$(p<0.05). When the two drugs were injected together at a low concentration, in which they did not display an effect, they displayed a significant analgesic reaction at CBX 1ug/kg and iso-PPADS 2.5ug/kg(p<0.05). When a gap injunction block using a low concentration of CBX and a low concentration P2X receptor antagonist was injected together, the pain suppressing effect was observed against the orofacial neuropathic pain mechanism. These results make it possible to determine that the gap junction block using CBX and the injection of the P2X receptor antagonist plays an important role in the pain management of the facial region.

• The Korean Journal of Pain
• /
• v.18 no.2
• /
• pp.107-112
• /
• 2005

Background: Nerve ligation injury may produce mechanical allodynia, but this can be reversed after an intrathecal administration of adenosine analogues. In many animal and human studies, ATP-sensitive potassium channel blockers have been known to reverse the antinociceptive effect of various drugs. This study was performed to evaluate the mechanical antiallodynic effects of spinal R-PIA (Adenosine A1 receptor agonist) and the reversal of these effects due to pretreatment with glibenclamide (ATP-sensitive potassium channel blocker). Thus, the relationship between the antiallodynic effects of R-PIA and ATP-sensitive potassium channel were investigated in a neuropathic model. Methods: Male Sprague Dawley rats were prepared by tightly ligating the left lumbar 5th and 6th spinal nerves and implantation of a chronic lumbar intrathecal catheter for drug administration. The mechanical allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hind paw. And the thresholds for paw withdrawal assessed. In study 1, either R-PIA (0.5, 1 and $2{\mu}g$) or saline were administered intrathecally for the examination of the antiallodynic effect of R-PIA. In study 2, glibenclamide (2, 5, 10 and 20 nM) was administered intrathecally 5 min prior to an R-PIA injection for investigation of the reversal of the antiallodynic effects of R-PIA. Results: The antiallodynic effect of R-PIA was produced in a dose dependent manner. In study 1, the paw withdrawal threshold was significantly increased with $2{\mu}g$ R-PIA (P < 0.05). In study 2, the paw withdrawal threshold with $2{\mu}g$ R-PIA was significantly decreased almost dose dependently by intrathecal pretreatment of 5, 10 and 20 nM glibenclamide (P < 0.05). Conclusions: These results demonstrated that an intrathecal injection of ATP-sensitive potassium channel blockers prior to an intrathecal injection of adenosine A1 receptors agonist had an antagonistic effect on R-PIA induced antiallodynia. The results suggest that the mechanism of mechanical antiallodynia, as induced by an intrathecal injection of R-PIA, may involve the ATP-sensitive potassium channel at both the spinal and supraspinal level in a rat nerve ligation injury model.

• The Journal of Korean Physical Therapy
• /
• v.22 no.3
• /
• pp.79-85
• /
• 2010

Purpose: Many trials for new therapeutic approaches such as stem cell-based transplantation have been conducted to improve the repair and regeneration of injured cord tissue and to restore functions following spinal cord injury (SCI) in animals and humans. Adipose tissue-derived stromal cells (ATSCs) have multi-lineage potential to differentiate into cells with neuron-like morphology. Most studies of stem cell transplantation therapy after SCI are focused on cellular regeneration and restoration of motor function, but not on unwanted effects after transplantation such as neuropathic pain. This study was focused on whether transplantation of ATSCs could facilitate or attenuate hindpaw pain responses to heat, cold and mechanical stimulation, as well as on improvement of locomotor function in a rat with SCI. Methods: A spinal cord injury rat model was produced using an NYU impactor by dropping a 10 g rod from a height of 25 mm on to the T9 segment. Human ATSCs (hATSCs; approximately $5{\times}10^5$ cells) or DMEM were injected into the perilesional area 9 days after the SCI. After transplantation, hindpaw withdrawal responses to heat, cold and mechanical allodynia were measured over 7 weeks. Motor recovery on the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and on the inclined plane test were also evaluated. Results: The present study demonstrated that increased hindpaw withdrawal responses to cold allodynia was observed in both groups after transplantation, but the development of cold-induced allodynia in the hATSC transplantation group was significantly larger than in the control group. The difference between the two groups in locomotor functional improvement after SCI was also significant. Conclusion: Careful consideration not only of optimal functional benefits but also of unintended side effects such as neuropathic pain is necessary before stem cell transplantation therapy after SCI.

• The Korean Journal of Pain
• /
• v.23 no.3
• /
• pp.179-185
• /
• 2010

Background: Vincristine-induced peripheral neuropathy is a major dose limiting side effect and thus effective therapeutic strategy is required. In this study, we investigated the antinociceptive effect of memantine and morphine on a vincristine-induced peripheral neuropathy model in rats. Methods: Male Sprague-Dawley rats weighing 220-240 g were used in all experiments. Rats subsequently received daily intraperitoneal injections of either vincristine sulfate (0.1 ml/kg/day) or saline (0.1 ml/kg/day) over 12 days, immediately following behavioral testing. For assessment of mechanical allodynia, mechanical stimuli using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of N-methyl-D-aspartate receptors antagonist (memantine; 2.5, 5, 10 mg/kg intraperitoneal), opioid agonist (morphine; 2.5, 5, 10 mg/kg intraperitoneal) and vehicle (saline) on vicristine-induced neuropathy were evaluated. Results: Mechanical allodynia developed over the course of ten daily injections of vincristine relative to groups receiving saline at the same time. Morphine abolished the reduction in paw withdrawal threshold compared to vehicle and produced dose-responsiveness. Only the highest dose of memantine (10 mg/kg) was able to increase paw withdrawal threshold compared to vehicle. Conclusions: Systemic morphine and memantine have an antinociceptive effect on the vincristine-induced peripheral neuropathy model in rats. These results suggest morphine and memantine may be an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

• The Korean Journal of Physiology and Pharmacology
• /
• v.14 no.6
• /
• pp.359-364
• /
• 2010

Many therapeutic roles have been proposed for sigma-1 receptor (Sig-1R), but the involvement of Sig-1R in neuropathic pain has currently not been well explored. The present study aimed to evaluate the anti-nociceptive effect of Sig-1R antagonist (BD1047) in a rat model of chronic compression of the dorsal root ganglion (CCD), which is a model of human foraminal stenosis and radicular pain. When stainless steel rods were inserted into the intervertebral foramen of lumbar vertebrae 4 and 5, the CCD developed reliable mechanical (from 3 day) and cold allodynia (from 1 day) as compared with the sham operation group. The spinal expressions of Sig-1R and phosphorylation of extracellular signal-regulated kinase (pERK) were significantly increased from day 3 to day 14 after CCD surgery, as is consistent with the manifestation of allodynia. The BD 1047 (10, 30, 100 mg/kg) administered on postoperative days 0~5 dose-dependently suppressed both the induction of allodynia and the elevation of the spinal pERK expression in a manner comparable with that of gabapentin (100 mg/kg). At 7 days post-CCD surgery, BD1047 (10, 30, 100 mg/kg) administration also produced anti-nociceptive effects on the mechanical and cold allodynia similar with those of gabapentin (100 mg/kg). Therefore, this data suggested that Sig-1R may play an important role in both the development and maintenance of CCD-induced neuropathy.

• Journal of Korean Neurosurgical Society
• /
• v.49 no.2
• /
• pp.83-91
• /
• 2011

Objective : Minocycline, a second-generation tetracycline-class antibiotic, has been well established to exert a neuroprotective effect in animal models and neurodegenerative disease through the inhibition of microglia. Here, we investigated the effects of minocycline on motor recovery and neuropathic pain in a rat model of spinal cord injury. Methods : To simulate spinal cord injury, the rats' spinal cords were hemisected at the 10th thoracic level (T10). Minocycline was injected intraperitoneally, and was administered 30 minutes prior surgery and every second postoperative day until sacrifice 28 days after surgery. Motor recovery was assessed via the Basso-Beattie-Bresnahan test Mechanical hyperalgesia was measured throughout the 28-day post -operative course via the von Frey test Microglial and astrocyte activation was assessed by immunohistochemical staining for ionized calcium binding adaptor molecule 1 (lba1) and glial fibrillary acidic protein (GFAP) at two sites: at the level of hemisection and at the 5th lumbar level (L5). Results : In rats, spinal cord hemisection reduced locomotor function and induced a mechanical hyperalgesia of the ipsilateral hind limb. The expression of lba1 and GFAP was also increased in the dorsal and ventral horns of the spinal cord at the site of hemisection and at the L5 level. Intraperitoneal injection of minocycline facilitated overall motor recovery and attenuated mechanical hyperalgesia. The expression of lba1 and GFAP in the spinal cord was also reduced in rats treated with minocycline. Conclusion : By inhibiting microglia and astrocyte activation, minocycline may facilitate motor recovery and attenuate mechanical hyperalgesia in individuals with spinal cord injuries.

• The Journal of Korean Medicine
• /
• v.25 no.3
• /
• pp.67-77
• /
• 2004

Objectives : Many studies have reported that acupuncture analgesia was mediated through the activation of peripheral and central opioid receptors. However, there has been little electrophysiological study on the adrenergic mechanism of acupuncture analgesia in chronic inflammatory and neuropathic pain. The present study was undertaken to elucidate the role of adrenoceptors in the production of acupuncture analgesia in the chronic pain model. Methods : In the rat with chronic inflammation and nerve injury, dorsal horn cell (DHC) responses to afferent C fiber stimulation were used as a pain index and changes in electroacupuncture (EA) analgesia were recorded before and after intravenous administration of selective adrenoceptor antagonists. EA stimulations (2Hz, 0.5msec, 3mA) were applied to the contralateral Zusanli point for 30 min. Results : EA stimulation induced long-lasting inhibition of DHC responses in the rat with chronic inflammation and nerve injury. In both models of inflammation and neuropathic pain, α-adrenoceptor antagonist (phentolamine) significantly attenuated an inhibitory effect of EA on DHC responses. Selective α2-adrenoceptor antagonist (yohimbine) also had a similar suppressive action on DHC responses to that of phentolamine. However, β-adrenoceptor antagonist (propranolol) did not have any inhibitory effect on DHC responses in either model of chronic pain. Conclusions : These experimental findings suggest that in rats with chronic pain, EA stimulation with low frequency and high intensity produced an analgesic effect which was mediated through an activation of α2-adrenoceptors.