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F117 ELECTROACUPUNCTURE PRODUCES ANTINOCICEPTION IN NONRESPONDER RATS TREATED WITH INTRAPERITONEAL AMITRIPTYLINE
108
POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
Results: DMH-treatment with bicuculline evoked escape behaviour followed by increase of nociceptive threshold in all animals. Synaptic blockade in MPFC with local microinjections of CoCl2 caused a significant decreased in fear-induced antinociception (P < 0.05). Furthermore, intra-MPFC pretreatment with AM 251 at different concentrations, significantly (P < 0.05) decreased the fearinduced antinociception. Conclusions: The effect of CoCl2 and AM 251 administrations in the MPFC decreasing the elevation of nociceptive threshold after panicinduced reactions suggests that the organization of antinociception that follows aversive states involves CB1 endocannabinoid receptors of MPFC. The present work was supported by FAPESP. Disclosure: None declared
F117 ELECTROACUPUNCTURE PRODUCES ANTINOCICEPTION IN NONRESPONDER RATS TREATED WITH INTRAPERITONEAL AMITRIPTYLINE R.S. Fais *, G.M. Reis, J.W.S. Silveira, Q.M. Dias, A.C. Rossaneis, W.A. Prado. Department of Pharmacology, Faculty of Medicine of Ribeir˜ ao Preto, University of S˜ ao Paulo, Ribeir˜ ao Preto, Brazil Background and Aims: Eletroacupuncture (EA) is widely used for relief of various types of pain, but some individuals do not respond to EA or had very short period of analgesia. Antidepressants, particularly the tricyclic (TCA) amitriptyline (AMI), are widely used for chronic pain management. Analgesia induced by EA and TCA may be complementary. The present study investigates whether the concomitant use of AMT combined with EA produces antinociception in non-responder rats. Methods: This study was approved by the Commission of Ethics in Animal Research, University of S˜ao Paulo (process142/2009). The pain induced by a surgical incision of the plantar aspect of the rat right hind paw was evaluated using an electronic Von Frey device. Male Wistar rats (160 g; n = 6 per group) previously selected as non-responders were used. They were anesthetized with isoflurane (0.5% in O2 ), received intraperitoneal saline (0.8 ml/Kg) or AMT (0.8 mg/kg), and 60 min later were submitted to a 20 min of real or sham 2 Hz EA applied bilaterally to the Zusanli (ST36) and Sanyinjiao (SP6) accupoints. Results: The surgical incision significantly reduced the mechanical threshold in the paw. In saline-treated animals the EA produced no significant reduction of the incision hyperalgesia in the incised paw as compared to the control (saline followed by sham EA). A significant reduction of post-incision pain was obtained after EA in AMT-treated rats, the effect lasting for 30 min (p < 0.0001). Conclusions: EA produced a significant analgesic effect in nonresponder rats pretreated with intraperitoneal AMT. FAPESP Disclosure: None declared
F118 ANTERIOR CINGULATE CORTEX CONTRIBUTES TO THE DESCENDING INHIBITORY MODULATION OF PAIN VIA RETROSPLENIAL CORTEX G.M. Reis *, A.C. Rossaneis, R.S. Fais, W.A. Prado. Pharmacology, University of S˜ ao Paulo, Ribeir˜ ao Preto, Brazil Background and Aims: In previous study were showed that the Electrical Stimulation (ES) of the Retrosplenial Cortex (RSC) produces antinociception without changes in the motor performance of the animals. There are evidence that show afferent and efferent inputs from the RSC to the Anterior Cingulate Cortex (ACC). This study examined whether the ACC is involved in the modulation of the antinociceptive effect of ES of the RSC. Methods: The experiments were conducted in accordance with the Ethical Committee for Animal Experimentation of the Faculty of Medicine of Ribeirao Preto/USP (No. 159/ 2007). Were implanted in rats a unipolar electrode in the RSC and a guide canulla in the ACC
those stands 7 days before tests. The formalin algesimeter test was used in the animals. Results: The subcutaneous injection of 5% formalin (50 ml) increased the number of spontaneous flinches at the injected paw and the total time during the animal lick it, if compared to rats injected with subcutaneous saline. During the first phase of the formalin test flinches and lick were inhibited by the prior stimulation of the RSC. The cortical stimulation did not change the second phase of the test. However, pre-treatment of ACC with CoCl2 in rats with ES of the RSC decreased significantly inflammatory nociceptive responses during the prolonged stage of the formalin test (p < 0.0001). Conclusions: The present results suggest that the ACC may have an inhibitory effect on the antinociceptive effect produced by the RSC. SUPPORT: FAPESP. Disclosure: None declared
F119 DEFICIENCY OF HYPOXIA INDUCIBLE FACTOR 1 ALPHA IN PRIMARY NEURONS INCREASES ACUTE PAIN SENSITIVITY BUT ATTENUATES CHRONIC HYPERSENSITIVITY IN MICE M. Kanngiesser1 *, H.Y. Lim1 , T. Myrczek1 , J. Blees2 , I. Tegeder1 . 1 Pharmazentrum Frankfurt/ZAFES, 2 Institute for Biochemistry I, University of Frankfurt, Frankfurt/Main, Germany Background and Aims: The transcription factor hypoxia inducible factor (HIF) is activated upon oxygen deficiency or redox stress and induces the expression of various genes in order to adapt to the stressful condition. Peripheral nerve injury causes redox stress which likely contributes to the development of chronic pain. Thus we were interested to investigate the role of HIF in this process. Methods: We deleted the alpha subunit, HIF1a specifically in neurons of the dorsal root ganglia by mating HIF1aflfl mice with SNScre mice and assessed nociception with various behavior tests and molecular analyses. Results: SNS-HIF1a−/− mice were more sensitive to acute heat pain than HIF1aflfl control mice. They also showed heightened first-phase nociceptive responses in the formalin and capsaicin tests and we observed intensified calcium fluxes in primary sensory neurons of SNS-HIF1a−/− upon stimulation of transient receptor potential (Trp) channels. In contrast to acute pain, nerve injury and CFA evoked chronic thermal hyperalgesia was reduced in SNS-HIF1a−/− mice compared with HIF1aflfl littermates suggesting that ongoing activation of HIF1a contributes to the maintenance of chronic pain, presumably by HIF1a-dependent transcriptional adaptations. In line with this hypothesis we observed that HIF1a dependent transcription of some pro-nociceptive genes was reduced in SNSHIF1a−/− mice after nociceptive stimulation. Conclusion: HIF1a is involved both in the setting of the baseline threshold of Trp channels and thereby acute pain and in the adaptation to chronic pain. While it lowers acute heat pain sensitivity it heightens chronic pain. The switch is likely caused by the transcriptional adaptation. Disclosure: None declared
F120 FUNCTIONAL SIGNIFICANCE OF SMALL GTPASE Rac1 IN PAIN TRANSMISSION IN THE MOUSE SPINAL DORSAL HORN K. Bali *, M. Simonetti, J. Lu, R. Kuner. Department of Molecular Pharmacology, Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany Background and Aims: A small GTPase Rac1 has been shown to regulate spine enlargement, activity-dependent dendrite growth and synaptic clustering of AMPAR during synapse maturation in vitro. Aim of present study is to understand the contribution of Rac1 to functional and structural plasticity at central synapses in pain pathways.
POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
Results: DMH-treatment with bicuculline evoked escape behaviour followed by increase of nociceptive threshold in all animals. Synaptic blockade in MPFC with local microinjections of CoCl2 caused a significant decreased in fear-induced antinociception (P < 0.05). Furthermore, intra-MPFC pretreatment with AM 251 at different concentrations, significantly (P < 0.05) decreased the fearinduced antinociception. Conclusions: The effect of CoCl2 and AM 251 administrations in the MPFC decreasing the elevation of nociceptive threshold after panicinduced reactions suggests that the organization of antinociception that follows aversive states involves CB1 endocannabinoid receptors of MPFC. The present work was supported by FAPESP. Disclosure: None declared
F117 ELECTROACUPUNCTURE PRODUCES ANTINOCICEPTION IN NONRESPONDER RATS TREATED WITH INTRAPERITONEAL AMITRIPTYLINE R.S. Fais *, G.M. Reis, J.W.S. Silveira, Q.M. Dias, A.C. Rossaneis, W.A. Prado. Department of Pharmacology, Faculty of Medicine of Ribeir˜ ao Preto, University of S˜ ao Paulo, Ribeir˜ ao Preto, Brazil Background and Aims: Eletroacupuncture (EA) is widely used for relief of various types of pain, but some individuals do not respond to EA or had very short period of analgesia. Antidepressants, particularly the tricyclic (TCA) amitriptyline (AMI), are widely used for chronic pain management. Analgesia induced by EA and TCA may be complementary. The present study investigates whether the concomitant use of AMT combined with EA produces antinociception in non-responder rats. Methods: This study was approved by the Commission of Ethics in Animal Research, University of S˜ao Paulo (process142/2009). The pain induced by a surgical incision of the plantar aspect of the rat right hind paw was evaluated using an electronic Von Frey device. Male Wistar rats (160 g; n = 6 per group) previously selected as non-responders were used. They were anesthetized with isoflurane (0.5% in O2 ), received intraperitoneal saline (0.8 ml/Kg) or AMT (0.8 mg/kg), and 60 min later were submitted to a 20 min of real or sham 2 Hz EA applied bilaterally to the Zusanli (ST36) and Sanyinjiao (SP6) accupoints. Results: The surgical incision significantly reduced the mechanical threshold in the paw. In saline-treated animals the EA produced no significant reduction of the incision hyperalgesia in the incised paw as compared to the control (saline followed by sham EA). A significant reduction of post-incision pain was obtained after EA in AMT-treated rats, the effect lasting for 30 min (p < 0.0001). Conclusions: EA produced a significant analgesic effect in nonresponder rats pretreated with intraperitoneal AMT. FAPESP Disclosure: None declared
F118 ANTERIOR CINGULATE CORTEX CONTRIBUTES TO THE DESCENDING INHIBITORY MODULATION OF PAIN VIA RETROSPLENIAL CORTEX G.M. Reis *, A.C. Rossaneis, R.S. Fais, W.A. Prado. Pharmacology, University of S˜ ao Paulo, Ribeir˜ ao Preto, Brazil Background and Aims: In previous study were showed that the Electrical Stimulation (ES) of the Retrosplenial Cortex (RSC) produces antinociception without changes in the motor performance of the animals. There are evidence that show afferent and efferent inputs from the RSC to the Anterior Cingulate Cortex (ACC). This study examined whether the ACC is involved in the modulation of the antinociceptive effect of ES of the RSC. Methods: The experiments were conducted in accordance with the Ethical Committee for Animal Experimentation of the Faculty of Medicine of Ribeirao Preto/USP (No. 159/ 2007). Were implanted in rats a unipolar electrode in the RSC and a guide canulla in the ACC
those stands 7 days before tests. The formalin algesimeter test was used in the animals. Results: The subcutaneous injection of 5% formalin (50 ml) increased the number of spontaneous flinches at the injected paw and the total time during the animal lick it, if compared to rats injected with subcutaneous saline. During the first phase of the formalin test flinches and lick were inhibited by the prior stimulation of the RSC. The cortical stimulation did not change the second phase of the test. However, pre-treatment of ACC with CoCl2 in rats with ES of the RSC decreased significantly inflammatory nociceptive responses during the prolonged stage of the formalin test (p < 0.0001). Conclusions: The present results suggest that the ACC may have an inhibitory effect on the antinociceptive effect produced by the RSC. SUPPORT: FAPESP. Disclosure: None declared
F119 DEFICIENCY OF HYPOXIA INDUCIBLE FACTOR 1 ALPHA IN PRIMARY NEURONS INCREASES ACUTE PAIN SENSITIVITY BUT ATTENUATES CHRONIC HYPERSENSITIVITY IN MICE M. Kanngiesser1 *, H.Y. Lim1 , T. Myrczek1 , J. Blees2 , I. Tegeder1 . 1 Pharmazentrum Frankfurt/ZAFES, 2 Institute for Biochemistry I, University of Frankfurt, Frankfurt/Main, Germany Background and Aims: The transcription factor hypoxia inducible factor (HIF) is activated upon oxygen deficiency or redox stress and induces the expression of various genes in order to adapt to the stressful condition. Peripheral nerve injury causes redox stress which likely contributes to the development of chronic pain. Thus we were interested to investigate the role of HIF in this process. Methods: We deleted the alpha subunit, HIF1a specifically in neurons of the dorsal root ganglia by mating HIF1aflfl mice with SNScre mice and assessed nociception with various behavior tests and molecular analyses. Results: SNS-HIF1a−/− mice were more sensitive to acute heat pain than HIF1aflfl control mice. They also showed heightened first-phase nociceptive responses in the formalin and capsaicin tests and we observed intensified calcium fluxes in primary sensory neurons of SNS-HIF1a−/− upon stimulation of transient receptor potential (Trp) channels. In contrast to acute pain, nerve injury and CFA evoked chronic thermal hyperalgesia was reduced in SNS-HIF1a−/− mice compared with HIF1aflfl littermates suggesting that ongoing activation of HIF1a contributes to the maintenance of chronic pain, presumably by HIF1a-dependent transcriptional adaptations. In line with this hypothesis we observed that HIF1a dependent transcription of some pro-nociceptive genes was reduced in SNSHIF1a−/− mice after nociceptive stimulation. Conclusion: HIF1a is involved both in the setting of the baseline threshold of Trp channels and thereby acute pain and in the adaptation to chronic pain. While it lowers acute heat pain sensitivity it heightens chronic pain. The switch is likely caused by the transcriptional adaptation. Disclosure: None declared
F120 FUNCTIONAL SIGNIFICANCE OF SMALL GTPASE Rac1 IN PAIN TRANSMISSION IN THE MOUSE SPINAL DORSAL HORN K. Bali *, M. Simonetti, J. Lu, R. Kuner. Department of Molecular Pharmacology, Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany Background and Aims: A small GTPase Rac1 has been shown to regulate spine enlargement, activity-dependent dendrite growth and synaptic clustering of AMPAR during synapse maturation in vitro. Aim of present study is to understand the contribution of Rac1 to functional and structural plasticity at central synapses in pain pathways.