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T134 FORMALIN-INDUCED PAIN AND CORTICOSTERONE STRESS RESPONSES IN PRENATALLY STRESSED INFANT MALE RATS: EFFECTS OF MATERNAL BUSPIRONE DURING PREGNANCY
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POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
T132 CONDITIONED PAIN MODULATION (CPM) AND COGNITIVE DISTRACTION FROM PAIN SHOW DIFFERENTIAL FRONTAL CORTICAL CONTROL R. Moont1,2 , Y. Crispel1 , R. Lev1 , D. Pud3 , D. Yarnitsky1,4 *. 1 Laboratory for Clinical Neurophysiology, Rambam Health Care Campus, 2 The Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, 3 Faculty of Social Welfare and Health Sciences, University of Haifa, 4 Department of Neurology, Rambam Health Care Campus, Haifa, Israel Background and Aims: Experimental paradigms to induce conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls or DNIC) and methods to cognitively distract subjects from pain have each highlighted activity changes in closely overlapping cortical areas. This is the first study to compare cortical activation changes during these two manipulations in the same experimental set-up. Methods: Phasic noxious heat stimuli were applied to the left volar forearm in 30 healthy young right handed males. These test stimuli were performed under conditioning hot-water pain to the right hand (CPM) and visual cognitive distraction tasks, both individually and simultaneously. Dynamic changes in localized cortical potentials evoked by the test stimuli were determined by investigating brief consecutive time windows of 50 ms using EEGbased sLORETA. Results: Previously we have shown that for CPM, there is increased activity in frontal cortical regions followed by reduced activation of the somatosensory areas, suggesting a pain inhibitory role for these frontal regions. We now observed that distraction caused a higher early activation of frontal areas (DLPFC, OFC and caudal ACC 250– 350 ms post-stimulus), yet lesser reduction in the somatosensory cortices, ACC, PCC, SMA and posterior insula after 350 ms poststimulus, compared to CPM. Both CPM and distraction similarly reduced subjective pain scores. Combining CPM and distraction further reduced pain ratings compared to CPM and distraction alone. Conclusions: The results suggest a dissimilarity in the mechanisms of pain modulation under CPM and distraction. Varying functional roles of the prefrontal cortex may explain the differential cortical activity under these two manipulations. Disclosure: None declared
T133 HISTAMINE H3 RECEPTOR MODULATES NOCICEPTION IN A RAT MODEL OF CHOLESTASIS P. Hasanein *. Bu-Ali Sina University, Hamedan, Iran Background and Aims: Cholestasis is associated with changes including analgesia. The histaminergic system regulates pain perception. The involvement of histamine H3 receptors in modulation of nociception in a model of elevated endogenous opioid tone, cholestasis, was investigated in this study using immepip and thioperamide as selective H3 receptor agonist and antagonist respectively. Methods: Cholestasis was induced by ligation of main bile duct using two ligatures and transsection the duct between them. Tailflick latencies were measured at 30 minutes after injection of the drugs in experimental groups. Results: Cholestatic rats had increased tail-flick latencies (TFLs) compared to non-cholestatics. Administration of immepip (5 and 30 mg/kg) and thioperamide (10 and 20 mg/kg) to the cholestatic groups significantly increased and decreased TFLs compared to the saline treated cholestatic group. Immepip antinociception in cholestatic animals was attenuated by co-administration of naloxone. Immepip and thioperamide injections into noncholestatic animals did not alter TFLs. At the doses used here, none of the drugs impaired motor coordination, as revealed by the rotarod test.
Conclusions: The present data show that the histamine H3 receptor system may be involved in the regulation of nociception during cholestasis in rats. Disclosure: None declared
T134 FORMALIN-INDUCED PAIN AND CORTICOSTERONE STRESS RESPONSES IN PRENATALLY STRESSED INFANT MALE RATS: EFFECTS OF MATERNAL BUSPIRONE DURING PREGNANCY I.P. Butkevich1 *, V.A. Mikhailenko1 , P.O. Semionov1 , T.R. Bagaeva2 . 1 Ontogeny of Nervous System, 2 Experimental Neuroendocrinology, I.P. Pavlov Institute of Physiology RAS, Saint Petersburg, Russia Background and Aims: Our recent paper demonstrates that maternal buspirone, a 5-HT1A receptor agonist, protects against the adverse effects of in utero stress on pain-related behavior in adult rat offspring. Using a similar maternal treatment with buspirone, we focus here on the infant stage characterized by stress hyporesponsiveness of the hypothalamo-pituitary-adrenal axis (HPA) which is intimately connected with the serotonergic system. Methods: Buspirone was chronically injected to rat dams before restraint stress during the last week of pregnancy. In 7-day-old male offspring, the number of flexes+shakes in the formalin test and plasma corticosterone levels were examined at 3, 9, 21, 30 and 60 min after injection of formalin. Results: Injection of formalin into the hindpaw immediately induced pain-related behavior and increased corticosterone to a greater extent than saline injection beginning with 21 min in all animals except buspirone+stress rats. Prenatally stressed rats had the greatest number of flexes+shakes. Maternal buspirone reversed this index and normalized pain-related behavior. The levels of corticosterone were significantly higher in buspirone+stress rats than in rats of other groups at 3 and 9 min of formalin-induced pain but during all the time intervals after saline injection into the hindpaw. In 24 hours after formalin test, the basal levels of corticosterone were higher than those before formalin test; there were no differences in corticosterone between the groups. Conclusions: Maternal treatment with buspirone during pregnancy evokes analgesic effect in formalin-induced pain in prenatally stressed 7-day-old offspring and disinhibits the HPA axis. Supported by grant RFBR 11–04–01381-a. Disclosure: None declared
T135 ANOTHER LOOK AT THE MECHANISM OF ACTION OF CRF RECEPTOR ANTAGONIST, SSR125543 P. Hassanzadeh1 *, A. Hassanzadeh2 . 1 Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti Univ. Med. Sci., Tehran, 2 Department of Molecular Biology, Azad University, Parand, Iran Background and Aims: Chronic pain syndromes including cancer pain have profound effects on the psychological well being of patients and are associated with increased rates of anxiety, depression and delirium. While the mainstay of pharmacological management of intense chronic pain is the aggressive use of narcotic analgesics, there is a growing appreciation for the role of adjuvant analgesic drugs in providing maximal comfort. In this context, psychotropic drugs such as tricyclic antidepressants, selective serotonin reuptake inhibitors, antipsychotics, and benzodiazepines have proved useful as adjuvant analgesic agents in the pharmacologic management of a wide variety of chronic pain syndromes. Corticotropin-releasing factor (CRF) antagonists which are used to treat mood disorders, have been recently suggested to exert analgesic and anti-inflammatory effects. Since pain and mood are closely linked, therefore studying the common molecular and cellular mechanisms as well as signal transduction pathways may lead to design more efficient therapeutic strategies.
POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
T132 CONDITIONED PAIN MODULATION (CPM) AND COGNITIVE DISTRACTION FROM PAIN SHOW DIFFERENTIAL FRONTAL CORTICAL CONTROL R. Moont1,2 , Y. Crispel1 , R. Lev1 , D. Pud3 , D. Yarnitsky1,4 *. 1 Laboratory for Clinical Neurophysiology, Rambam Health Care Campus, 2 The Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, 3 Faculty of Social Welfare and Health Sciences, University of Haifa, 4 Department of Neurology, Rambam Health Care Campus, Haifa, Israel Background and Aims: Experimental paradigms to induce conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls or DNIC) and methods to cognitively distract subjects from pain have each highlighted activity changes in closely overlapping cortical areas. This is the first study to compare cortical activation changes during these two manipulations in the same experimental set-up. Methods: Phasic noxious heat stimuli were applied to the left volar forearm in 30 healthy young right handed males. These test stimuli were performed under conditioning hot-water pain to the right hand (CPM) and visual cognitive distraction tasks, both individually and simultaneously. Dynamic changes in localized cortical potentials evoked by the test stimuli were determined by investigating brief consecutive time windows of 50 ms using EEGbased sLORETA. Results: Previously we have shown that for CPM, there is increased activity in frontal cortical regions followed by reduced activation of the somatosensory areas, suggesting a pain inhibitory role for these frontal regions. We now observed that distraction caused a higher early activation of frontal areas (DLPFC, OFC and caudal ACC 250– 350 ms post-stimulus), yet lesser reduction in the somatosensory cortices, ACC, PCC, SMA and posterior insula after 350 ms poststimulus, compared to CPM. Both CPM and distraction similarly reduced subjective pain scores. Combining CPM and distraction further reduced pain ratings compared to CPM and distraction alone. Conclusions: The results suggest a dissimilarity in the mechanisms of pain modulation under CPM and distraction. Varying functional roles of the prefrontal cortex may explain the differential cortical activity under these two manipulations. Disclosure: None declared
T133 HISTAMINE H3 RECEPTOR MODULATES NOCICEPTION IN A RAT MODEL OF CHOLESTASIS P. Hasanein *. Bu-Ali Sina University, Hamedan, Iran Background and Aims: Cholestasis is associated with changes including analgesia. The histaminergic system regulates pain perception. The involvement of histamine H3 receptors in modulation of nociception in a model of elevated endogenous opioid tone, cholestasis, was investigated in this study using immepip and thioperamide as selective H3 receptor agonist and antagonist respectively. Methods: Cholestasis was induced by ligation of main bile duct using two ligatures and transsection the duct between them. Tailflick latencies were measured at 30 minutes after injection of the drugs in experimental groups. Results: Cholestatic rats had increased tail-flick latencies (TFLs) compared to non-cholestatics. Administration of immepip (5 and 30 mg/kg) and thioperamide (10 and 20 mg/kg) to the cholestatic groups significantly increased and decreased TFLs compared to the saline treated cholestatic group. Immepip antinociception in cholestatic animals was attenuated by co-administration of naloxone. Immepip and thioperamide injections into noncholestatic animals did not alter TFLs. At the doses used here, none of the drugs impaired motor coordination, as revealed by the rotarod test.
Conclusions: The present data show that the histamine H3 receptor system may be involved in the regulation of nociception during cholestasis in rats. Disclosure: None declared
T134 FORMALIN-INDUCED PAIN AND CORTICOSTERONE STRESS RESPONSES IN PRENATALLY STRESSED INFANT MALE RATS: EFFECTS OF MATERNAL BUSPIRONE DURING PREGNANCY I.P. Butkevich1 *, V.A. Mikhailenko1 , P.O. Semionov1 , T.R. Bagaeva2 . 1 Ontogeny of Nervous System, 2 Experimental Neuroendocrinology, I.P. Pavlov Institute of Physiology RAS, Saint Petersburg, Russia Background and Aims: Our recent paper demonstrates that maternal buspirone, a 5-HT1A receptor agonist, protects against the adverse effects of in utero stress on pain-related behavior in adult rat offspring. Using a similar maternal treatment with buspirone, we focus here on the infant stage characterized by stress hyporesponsiveness of the hypothalamo-pituitary-adrenal axis (HPA) which is intimately connected with the serotonergic system. Methods: Buspirone was chronically injected to rat dams before restraint stress during the last week of pregnancy. In 7-day-old male offspring, the number of flexes+shakes in the formalin test and plasma corticosterone levels were examined at 3, 9, 21, 30 and 60 min after injection of formalin. Results: Injection of formalin into the hindpaw immediately induced pain-related behavior and increased corticosterone to a greater extent than saline injection beginning with 21 min in all animals except buspirone+stress rats. Prenatally stressed rats had the greatest number of flexes+shakes. Maternal buspirone reversed this index and normalized pain-related behavior. The levels of corticosterone were significantly higher in buspirone+stress rats than in rats of other groups at 3 and 9 min of formalin-induced pain but during all the time intervals after saline injection into the hindpaw. In 24 hours after formalin test, the basal levels of corticosterone were higher than those before formalin test; there were no differences in corticosterone between the groups. Conclusions: Maternal treatment with buspirone during pregnancy evokes analgesic effect in formalin-induced pain in prenatally stressed 7-day-old offspring and disinhibits the HPA axis. Supported by grant RFBR 11–04–01381-a. Disclosure: None declared
T135 ANOTHER LOOK AT THE MECHANISM OF ACTION OF CRF RECEPTOR ANTAGONIST, SSR125543 P. Hassanzadeh1 *, A. Hassanzadeh2 . 1 Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti Univ. Med. Sci., Tehran, 2 Department of Molecular Biology, Azad University, Parand, Iran Background and Aims: Chronic pain syndromes including cancer pain have profound effects on the psychological well being of patients and are associated with increased rates of anxiety, depression and delirium. While the mainstay of pharmacological management of intense chronic pain is the aggressive use of narcotic analgesics, there is a growing appreciation for the role of adjuvant analgesic drugs in providing maximal comfort. In this context, psychotropic drugs such as tricyclic antidepressants, selective serotonin reuptake inhibitors, antipsychotics, and benzodiazepines have proved useful as adjuvant analgesic agents in the pharmacologic management of a wide variety of chronic pain syndromes. Corticotropin-releasing factor (CRF) antagonists which are used to treat mood disorders, have been recently suggested to exert analgesic and anti-inflammatory effects. Since pain and mood are closely linked, therefore studying the common molecular and cellular mechanisms as well as signal transduction pathways may lead to design more efficient therapeutic strategies.