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214 THE ANALGESIC ACTION OF PULSED RADIOFREQUENCY APPLIED TO DORSAL ROOT GANGLION ON NEUROPATHIC PAIN IN RATS
Posters / European Journal of Pain Supplements 4 (2010) 47–146
injections of paclitaxel. This model is reliable enough for efficacy assessment of novel analgesics. 214 THE ANALGESIC ACTION OF PULSED RADIOFREQUENCY APPLIED TO DORSAL ROOT GANGLION ON NEUROPATHIC PAIN IN RATS Y.-R. Wen1,2 , M.-L. Lin3,4 , C.-W. Lin4 , S.-H. Huang5 . 1 Anesthesiology, Shin-Kong Wu Ho-Su Memorial Hospital, 2 School of Medicine, Taipei Medical University, 3 Pain Center, Taipei City Hospital, 4 Institute of Biomedical Engineering, National Taiwan University, 5 Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan R.O.C. Introduction: Radiofrequency lesions have been widely used to treat chronic pain syndromes by high-temperature ablation of nerve tissues. However, the efficacy and mechanism of low-temperature pulsed-radiofrequency (p-RF) procedure are largely unknown. Objectives: We applied p-RF to L5 DRG to examine the analgesic effect in a neuropathic pain model and the neurobiological changes in the spinal cord. Methods: Under anesthesia, a modified spinal nerve ligation (SNL) model was conducted in the SD rats. After L5 ligation, p-RF electrode was introduced approximate to the ipsilateral L5 DRG. Pulse stimulation with 500 kHz square or sine waves at a parameter of 2Hz, 5 ms was delivered for 5 min. Mechanical allodynia of the nerve-injured paw was evaluated and the values were compared between the p-RF group and the sham operated group. Meanwhile, pERK, p-p38 and Fos activities in the spinal dorsal horn were analyzed by immunohistochemical method. Results: The p-RF electrode could be easily inserted into the foramen. A transient neurotrauma was shown with behavioral and neurostaining evidence. DRG treatment produced anti-allodynic effect for 3 days after SNL, and p-RF of sine waveforms exhibited better analgesia than that of square waveforms. pERK and Fos expression had no significant difference between the p-RF group and the sham group, but microglial p38 activation was inhibited in the p-RF group. Conclusions: Single p-RF stimulation at the DRG produced significant reduction of neuropathic pain in the rats. Immunostaining analysis showed that p-p38 suppression in the spinal microglia may partially contribute to the analgesic functions of p-RF treatment. 215 THE INFLUENCE OF PERIPHERAL NERVE INJURY ON PSD MRNA EXPRESSION IN SPINAL CORD AND HIPPOCAMPUS OF RATS L. Xu1 , L. Wei1 , Y. Jianying2 , H. Yuguang1 , Pain Management Group in PUMCH. 1 Anesthesiology, Peking Union Medical College Hospital, 2 Anesthesiology, Beijing TongRen Hospital, Beijing, China Introduction: The post-synaptic density (PSD), which is a specialization of the cytoskeleton at the synaptic junction in the central nervous system (CNS), is believed to play a potential role in the organization of receptors and related proteins involved in synaptic signaling. It is also known that peripheral nerve injury such as chronic sciatic nerve constriction (CCI) produces neuropathic pain by spinal central mechanism. Therefore, we explored the changing of PSD expression in CNS of CCI rats. Objectives: To determine the expression alterations of PSD after peripheral nerve injury and to explore the CNS mechanism of neuropathic pain. Methods: Male Sprague-Dawley rats were divided into three groups: 1. Naive control rats, 2. Sham surgery rats, 3. CCI surgery rats. Mechanical allodynia was tested by a series of von Frey hairs 3, 7, and 14 days after surgery. All rats were killed at different times after surgery to examine PSD (including CaMKIIa, CaMKIIb, PSD-95, PSD-93 and its subunits) expression level changes in spinal cord and hippocampus by RT-PCR.
63
Results: The expression of PSD mRNA were significantly increased after CCI surgery compared with time-matched sham surgery rats (P < 0.05). Moreover, the expression level of PSD-95 and PSD-93 elevated with the decrease of mechanical paw withdrawal threshold after sciatic nerve ligation. However, these changes happened in spinal cord but not in hippocampus. Conclusions: Peripheral nerve injury induced neuropathic pain and increased PSD expression in spinal cord. The results suggested that PSD might play a key role in the central mechanism of neuropathic pain. 216 A NEW SELECTIVE SIGMA-1 RECEPTOR ANTAGONIST (S1RA) REDUCES NEUROPATHIC PAIN BEHAVIORS AND ACTIVITY-INDUCED SPINAL SENSITISATION D. Zamanillo1 , L. Romero1 , J. Burgueno ˜ 1 , X. Nadal2 , A. Dordal1 , G. Gris1 , A. Vidal1 , M. Laloya1 , C. Segales ´ 1 , E. Portillo-Salido1 , J.M. Baeyens3 , J.A. Lopez-Garc´ ´ ıa4 , R. Maldonado2 , J.M. Vela1 . 1 Pharmacology, ESTEVE, 2 Laboratory of Neuropharmacology, Facultat de Ci`encies de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, 3 Pharmacology and Institute of Neuroscience, Faculty of Medicine, Universidad de Granada, Granada, 4 Physiology, Faculty of Medicine, Universidad de Alcal´ a de Henares, Madrid, Spain Recently, we have shown a reduction of neuropathic pain behaviors secondary to nerve injury in the sigma-1 receptor (s1R) knockout mice. Furthermore, electrophysiological recordings in spinal cords demonstrated that wind-up responses after stimulation of the dorsal root were attenuated in s1R knockout mice. These findings identify s1R as a constituent of the mechanisms modulating activity induced sensitization in pain pathways and point to s1R as a new target for drugs designed to alleviate neuropathic pain. Given the therapeutic potential, we have developed a selective s1R antagonist (S1RA). We describe here the main pharmacological in vitro and in vivo properties of S1RA. In vitro data are presented describing high s1R affinity and selectivity as well as antagonistic functional profile at s1Rs for S1RA. Electrophysiological wind-up responses in isolated spinal cords from wild type mice were attenuated in the presence of S1RA, as expected based on findings in s1R knockout mice. In vivo, S1RA reduced pain behaviors when administered systemically to wild-type mice exposed to chemical sensitization of pain pathways (i.e., intraplantar formalin and capsaicin injection). Interestingly, mechanical and thermal hyperalgesia were also reduced when S1RA was systemically administered to mice suffering from neuropathic pain (i.e., nerve injury-induced neuropathic pain). Altogether, S1RA represents a new compound with analgesic properties acting through the s1R. 217 ELECTROACUPUNCTURE IS BETTER THAN COX-2 INHIBITOR CELECOXIB FOR NEUROPATHIC PAIN IN RAT H.-Q. Zhang, W.-K. Lau, Y.-M. Lau, S.-C. Wong, T.-P. Yip. Hong Kong Baptist University, Hong Kong, Hong Kong S.A.R. Introduction: Recent studies have found that COX-2 expression in the dorsal root ganglia and spinal dorsal horn increases after spinal nerve ligation (SNL) or other nerve injuries, indicating that it may play an important role in the neuropathic pain. Thus COX-2 inhibitors are now used to treat some neuropathic pain conditions. Our recent study has shown that electroacupuncture (EA) may alleviate neuropathic hypersensitivity, and it also inhibited spinal COX-2 expression. Objectives: To compare the analgesic effects between EA and COX-2 inhibitor Celecoxib after SNL. Methods: After L5 SNL, the rats were treated either with 2Hz EA (0.5–1-2 mA stepwise) applied to Zusanli (ST36) and Sanyinjiao (SP6) 4 times (10 mins each) over 22 days, or Celecoxib (3 mg/kg/day) fed daily. Paw-withdrawal-threshold (PWT) to mechanical stimulation and paw-withdrawal-latency (PWL)
injections of paclitaxel. This model is reliable enough for efficacy assessment of novel analgesics. 214 THE ANALGESIC ACTION OF PULSED RADIOFREQUENCY APPLIED TO DORSAL ROOT GANGLION ON NEUROPATHIC PAIN IN RATS Y.-R. Wen1,2 , M.-L. Lin3,4 , C.-W. Lin4 , S.-H. Huang5 . 1 Anesthesiology, Shin-Kong Wu Ho-Su Memorial Hospital, 2 School of Medicine, Taipei Medical University, 3 Pain Center, Taipei City Hospital, 4 Institute of Biomedical Engineering, National Taiwan University, 5 Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan R.O.C. Introduction: Radiofrequency lesions have been widely used to treat chronic pain syndromes by high-temperature ablation of nerve tissues. However, the efficacy and mechanism of low-temperature pulsed-radiofrequency (p-RF) procedure are largely unknown. Objectives: We applied p-RF to L5 DRG to examine the analgesic effect in a neuropathic pain model and the neurobiological changes in the spinal cord. Methods: Under anesthesia, a modified spinal nerve ligation (SNL) model was conducted in the SD rats. After L5 ligation, p-RF electrode was introduced approximate to the ipsilateral L5 DRG. Pulse stimulation with 500 kHz square or sine waves at a parameter of 2Hz, 5 ms was delivered for 5 min. Mechanical allodynia of the nerve-injured paw was evaluated and the values were compared between the p-RF group and the sham operated group. Meanwhile, pERK, p-p38 and Fos activities in the spinal dorsal horn were analyzed by immunohistochemical method. Results: The p-RF electrode could be easily inserted into the foramen. A transient neurotrauma was shown with behavioral and neurostaining evidence. DRG treatment produced anti-allodynic effect for 3 days after SNL, and p-RF of sine waveforms exhibited better analgesia than that of square waveforms. pERK and Fos expression had no significant difference between the p-RF group and the sham group, but microglial p38 activation was inhibited in the p-RF group. Conclusions: Single p-RF stimulation at the DRG produced significant reduction of neuropathic pain in the rats. Immunostaining analysis showed that p-p38 suppression in the spinal microglia may partially contribute to the analgesic functions of p-RF treatment. 215 THE INFLUENCE OF PERIPHERAL NERVE INJURY ON PSD MRNA EXPRESSION IN SPINAL CORD AND HIPPOCAMPUS OF RATS L. Xu1 , L. Wei1 , Y. Jianying2 , H. Yuguang1 , Pain Management Group in PUMCH. 1 Anesthesiology, Peking Union Medical College Hospital, 2 Anesthesiology, Beijing TongRen Hospital, Beijing, China Introduction: The post-synaptic density (PSD), which is a specialization of the cytoskeleton at the synaptic junction in the central nervous system (CNS), is believed to play a potential role in the organization of receptors and related proteins involved in synaptic signaling. It is also known that peripheral nerve injury such as chronic sciatic nerve constriction (CCI) produces neuropathic pain by spinal central mechanism. Therefore, we explored the changing of PSD expression in CNS of CCI rats. Objectives: To determine the expression alterations of PSD after peripheral nerve injury and to explore the CNS mechanism of neuropathic pain. Methods: Male Sprague-Dawley rats were divided into three groups: 1. Naive control rats, 2. Sham surgery rats, 3. CCI surgery rats. Mechanical allodynia was tested by a series of von Frey hairs 3, 7, and 14 days after surgery. All rats were killed at different times after surgery to examine PSD (including CaMKIIa, CaMKIIb, PSD-95, PSD-93 and its subunits) expression level changes in spinal cord and hippocampus by RT-PCR.
63
Results: The expression of PSD mRNA were significantly increased after CCI surgery compared with time-matched sham surgery rats (P < 0.05). Moreover, the expression level of PSD-95 and PSD-93 elevated with the decrease of mechanical paw withdrawal threshold after sciatic nerve ligation. However, these changes happened in spinal cord but not in hippocampus. Conclusions: Peripheral nerve injury induced neuropathic pain and increased PSD expression in spinal cord. The results suggested that PSD might play a key role in the central mechanism of neuropathic pain. 216 A NEW SELECTIVE SIGMA-1 RECEPTOR ANTAGONIST (S1RA) REDUCES NEUROPATHIC PAIN BEHAVIORS AND ACTIVITY-INDUCED SPINAL SENSITISATION D. Zamanillo1 , L. Romero1 , J. Burgueno ˜ 1 , X. Nadal2 , A. Dordal1 , G. Gris1 , A. Vidal1 , M. Laloya1 , C. Segales ´ 1 , E. Portillo-Salido1 , J.M. Baeyens3 , J.A. Lopez-Garc´ ´ ıa4 , R. Maldonado2 , J.M. Vela1 . 1 Pharmacology, ESTEVE, 2 Laboratory of Neuropharmacology, Facultat de Ci`encies de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, 3 Pharmacology and Institute of Neuroscience, Faculty of Medicine, Universidad de Granada, Granada, 4 Physiology, Faculty of Medicine, Universidad de Alcal´ a de Henares, Madrid, Spain Recently, we have shown a reduction of neuropathic pain behaviors secondary to nerve injury in the sigma-1 receptor (s1R) knockout mice. Furthermore, electrophysiological recordings in spinal cords demonstrated that wind-up responses after stimulation of the dorsal root were attenuated in s1R knockout mice. These findings identify s1R as a constituent of the mechanisms modulating activity induced sensitization in pain pathways and point to s1R as a new target for drugs designed to alleviate neuropathic pain. Given the therapeutic potential, we have developed a selective s1R antagonist (S1RA). We describe here the main pharmacological in vitro and in vivo properties of S1RA. In vitro data are presented describing high s1R affinity and selectivity as well as antagonistic functional profile at s1Rs for S1RA. Electrophysiological wind-up responses in isolated spinal cords from wild type mice were attenuated in the presence of S1RA, as expected based on findings in s1R knockout mice. In vivo, S1RA reduced pain behaviors when administered systemically to wild-type mice exposed to chemical sensitization of pain pathways (i.e., intraplantar formalin and capsaicin injection). Interestingly, mechanical and thermal hyperalgesia were also reduced when S1RA was systemically administered to mice suffering from neuropathic pain (i.e., nerve injury-induced neuropathic pain). Altogether, S1RA represents a new compound with analgesic properties acting through the s1R. 217 ELECTROACUPUNCTURE IS BETTER THAN COX-2 INHIBITOR CELECOXIB FOR NEUROPATHIC PAIN IN RAT H.-Q. Zhang, W.-K. Lau, Y.-M. Lau, S.-C. Wong, T.-P. Yip. Hong Kong Baptist University, Hong Kong, Hong Kong S.A.R. Introduction: Recent studies have found that COX-2 expression in the dorsal root ganglia and spinal dorsal horn increases after spinal nerve ligation (SNL) or other nerve injuries, indicating that it may play an important role in the neuropathic pain. Thus COX-2 inhibitors are now used to treat some neuropathic pain conditions. Our recent study has shown that electroacupuncture (EA) may alleviate neuropathic hypersensitivity, and it also inhibited spinal COX-2 expression. Objectives: To compare the analgesic effects between EA and COX-2 inhibitor Celecoxib after SNL. Methods: After L5 SNL, the rats were treated either with 2Hz EA (0.5–1-2 mA stepwise) applied to Zusanli (ST36) and Sanyinjiao (SP6) 4 times (10 mins each) over 22 days, or Celecoxib (3 mg/kg/day) fed daily. Paw-withdrawal-threshold (PWT) to mechanical stimulation and paw-withdrawal-latency (PWL)