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165 ELECTRICAL STIMULATION OF THE INSULAR CORTEX DIMINISHES NOCICEPTIVE BEHAVIOUR AND INCREASES THETA FREQUENCY BAND IN RATS
Poster Sessions / European Journal of Pain 13 (2009) S55–S285
164 DEPRESSIVE-LIKE BEHAVIOUR IN NEUROPATHIC PAIN IS ASSOCIATED WITH DECREASED GLIAL AND NEURONAL CELLS IN THE PREFRONTAL CORTEX OF THE RAT V. Cardoso, F. Pinto-Ribeiro *, N. Sousa, J.J. Cerqueira, A. Almeida. Life and Health Sciences Research Institute, Braga, Portugal Depression is commonly observed in patients with chronic pain. Pain can be divided into a sensitive and emotional component processed by different neural circuitries; the emotional component is largely modulated by the structures within the limbic system. The consolidation of pain-related aversive behaviours is attributed to the anterior cingulated cortex, where it has been showed that decreased glial cell density is associated with the development of depressive-like behaviour in stressed animals. Our aim was to investigate the possibility of an association between alterations in cell density in the prefrontal cortex (PFC) and depressive-like behaviour in neuropathic rats. One and two months after inducing spared nerve injury (SNI), neuropathic animals were tested for the presence of depressive-like behaviour (forced-swimming test) and evaluation of locomotor activity (open field test). Stereological analysis of the PFC considered three major areas, the cingulated I (CgI), the pre-limbic (PrL) and the infralimbic (IL) cortices, which were subdivided in three cortical areas, for quantification. The development of depressive-like behaviour was paralleled by a decrease in the number of glial cells in layer II (external granular layer) of the CgI, PrL and IL. Moreover there was a specific decrease in neurone numbers in IL layer II. These data indicate that alterations of glial and neuronal cell content in the PFC contribute to the development of depressive-like behaviour. 165 ELECTRICAL STIMULATION OF THE INSULAR CORTEX DIMINISHES NOCICEPTIVE BEHAVIOUR AND INCREASES THETA FREQUENCY BAND IN RATS 1 K. Simon-Arceo ´ *, U. Coffeen1,2 , M. Palma1 , J.M. Ortega-Legaspi1 , A. Lopez-Avila1,3 , F. Pellicer1 . 1 Instituto Nacional de Psiquiatr´ıa Ram´ on de la Fuente, Mexico, Mexico; 2 Departamento de Farmacobiolog´ıa, Cinvestav-Sede Sur, Mexico, Mexico; 3 Departamento de Atenci´ on a la Salud, Universidad Aut´ onoma Metropolitana, Mexico, Mexico
The role of the insular cortex (IC) in pain processing has been suggested in both human and animal studies. Electrical stimulation of the human IC induces painful sensations. Also, painful stimuli activate the IC. The aim of this work is to determine if electrical stimulation of the IC modifies nociceptive behaviour and if this modification correlates with EEG features. For rat IC stimulation, a bipolar steel electrode was implanted. The stimulation parameters were: square pulses of 0.2 ms at 100 Hz for 1 s every 5 s. The stimulation was applied 10 min daily over 5 days. Immediately after electrical stimulation, acute thermal stimulation was applied with a plantar test apparatus to measure nociception as paw withdrawal latency (PWL) and EEG recordings were performed. After five days of IC electrical stimulation, secondary inflammatory hyperalgesia was induced by an intraplantar injection of carrageenan (CAR) 1% in 250 mml and PWL was measured. The results show that IC stimulation significantly increases PWL after the induction of both acute thermonociception and secondary inflammatory hyperalgesia. Also, the change in spectral measures of electrical activity in the IC consisted of increased relative power of the theta frequency band (3–7 Hz). IC increases potency in low frequencies which may correlate with a decreased nociceptive behaviour. This work highlights the role of the IC in the modulation of acute thermonociception and secondary inflammatory hyperalgesia.
S57
166 INTRATHECAL INJECTION OF A CANNABINOID CB2 RECEPTOR SELECTIVE AGONIST GW405833 BLOCKS INDUCTION OF ALLODYNIA BY SCIATIC INFLAMMATORY NEURITIS (SIN) J. Ashton1 *, P. Brownjohn1 , J. Wilkerson2 , M. Dowie3 , M. Glass3 , E. Milligan2 . 1 Department of Pharmacology & Toxicology, University of Otago., Dunedin, New Zealand; 2 Department of Neurosciences, School of Medicine, University of Mexico., Albuquerque, United States; 3 Department of Pharmacology, University of Auckland., Auckland, New Zealand Intrathecal injection of a Cannabinoid CB2 Receptor Selective Agonist GW405833 Blocks Induction of Allodynia by Sciatic Inflammatory Neuritis (SIN). Cannabinoids have been shown to ameriolate neuropathic pain through both the CB1 receptor, found on neurons and the CB2R receptor, found on immune cells in the CNS. CB2-selective agonists reduce pain after peripheral nerve injury, and CB2 activation does not cause the psychoactivity associated with CB1 activation, making CB2 agonists attractive candidates for treating neuropathic pain. However, the precise mechanism of action in the pain pathways by CB2 remains controversial. Sciatic inflammatory neuritis (SIN) lead to allodynia. We found that (intrathecal, i.t.) injection of GW405833 was efficacious in blocking the development of allodynia after SIN, assessed using von Frey filaments. However, immunohistochemical analysis using a range of polyclonal antibodies for CB2, and mRNA in situ hybridization of spinal cords failed to show any evidence of CB2 expression in the spinal cord at the acute stage of injury. Ongoing studies are aimed at evaluating the ex vivo effect of GW405833 on DRG neuron action potentials and on spinal cord G-protein activation, in order to determine the mechanism of action of GW405833 in the spinal cord in blocking the development of allodynia in SIN. 167 BEHAVIOURAL AND BIOCHEMICAL EFFECTS OF THE FATTY ACID AMIDE HYDROLASE INHIBITOR URB597 IN THE RAT FORMALIN TEST G. Ford1 *, B. Harhen2 , E. Tully1 , A. Mulcahy1 , D. Finn1 . 1 Department of Pharmacology and Therapeutics, NCBES Neuroscience Cluster and Centre for Pain Research, National University of Ireland, Galway, Galway, Ireland; 2 Centre for Bioanalytical Sciences, National University of Ireland, Galway, Galway, Ireland Fatty acid amide hydrolase (FAAH) catalyses the degradation of several endocannabinoids and fatty acid amides which are known to modulate nociception and hippocampal activity. Here, the effect of systemic administration of the FAAH inhibitor URB597 on formalinevoked nociceptive behaviour in rats was investigated. Associated changes in endocannabinoid/fatty acid amide concentrations in the ventral hippocampus and brain monoamines in regions comprising the descending inhibitory pain pathway were also determined. Intraplantar injection of formalin (50 ml 2.5% into the right hindpaw under brief 3% isoflurane anaesthesia) was used to evoke nociceptive behaviour in male Lister-Hooded rats (n = 7/group) which was scored for a 30 minute period (30–60 min postformalin). Immediately following formalin, animals received an intra-peritoneal injection of either the FAAH inhibitor URB597 (0.3 mg/kg), the cannabinoid-1 receptor antagonist rimonabant (1 mg/kg), or vehicle (ethanol:crempohor:saline). Post-mortem brain tissue monoamine levels were measured by HPLC coupled to electrochemical detection and endocannabinoid/fatty acid amide concentrations were determined by LC/MS/MS. Data were analysed by ANOVA and Tukey’s or Student-Newman-Keuls post-hoc test. URB597 significantly reduced formalin-evoked nociceptive behaviour over the entire trial, an effect accompanied by elevated levels of oleoylethanolamide and palmitoylethanolamide in the ventral hippocampus compared with vehicle-treated animals. Monoamine levels in all regions examined were not altered
164 DEPRESSIVE-LIKE BEHAVIOUR IN NEUROPATHIC PAIN IS ASSOCIATED WITH DECREASED GLIAL AND NEURONAL CELLS IN THE PREFRONTAL CORTEX OF THE RAT V. Cardoso, F. Pinto-Ribeiro *, N. Sousa, J.J. Cerqueira, A. Almeida. Life and Health Sciences Research Institute, Braga, Portugal Depression is commonly observed in patients with chronic pain. Pain can be divided into a sensitive and emotional component processed by different neural circuitries; the emotional component is largely modulated by the structures within the limbic system. The consolidation of pain-related aversive behaviours is attributed to the anterior cingulated cortex, where it has been showed that decreased glial cell density is associated with the development of depressive-like behaviour in stressed animals. Our aim was to investigate the possibility of an association between alterations in cell density in the prefrontal cortex (PFC) and depressive-like behaviour in neuropathic rats. One and two months after inducing spared nerve injury (SNI), neuropathic animals were tested for the presence of depressive-like behaviour (forced-swimming test) and evaluation of locomotor activity (open field test). Stereological analysis of the PFC considered three major areas, the cingulated I (CgI), the pre-limbic (PrL) and the infralimbic (IL) cortices, which were subdivided in three cortical areas, for quantification. The development of depressive-like behaviour was paralleled by a decrease in the number of glial cells in layer II (external granular layer) of the CgI, PrL and IL. Moreover there was a specific decrease in neurone numbers in IL layer II. These data indicate that alterations of glial and neuronal cell content in the PFC contribute to the development of depressive-like behaviour. 165 ELECTRICAL STIMULATION OF THE INSULAR CORTEX DIMINISHES NOCICEPTIVE BEHAVIOUR AND INCREASES THETA FREQUENCY BAND IN RATS 1 K. Simon-Arceo ´ *, U. Coffeen1,2 , M. Palma1 , J.M. Ortega-Legaspi1 , A. Lopez-Avila1,3 , F. Pellicer1 . 1 Instituto Nacional de Psiquiatr´ıa Ram´ on de la Fuente, Mexico, Mexico; 2 Departamento de Farmacobiolog´ıa, Cinvestav-Sede Sur, Mexico, Mexico; 3 Departamento de Atenci´ on a la Salud, Universidad Aut´ onoma Metropolitana, Mexico, Mexico
The role of the insular cortex (IC) in pain processing has been suggested in both human and animal studies. Electrical stimulation of the human IC induces painful sensations. Also, painful stimuli activate the IC. The aim of this work is to determine if electrical stimulation of the IC modifies nociceptive behaviour and if this modification correlates with EEG features. For rat IC stimulation, a bipolar steel electrode was implanted. The stimulation parameters were: square pulses of 0.2 ms at 100 Hz for 1 s every 5 s. The stimulation was applied 10 min daily over 5 days. Immediately after electrical stimulation, acute thermal stimulation was applied with a plantar test apparatus to measure nociception as paw withdrawal latency (PWL) and EEG recordings were performed. After five days of IC electrical stimulation, secondary inflammatory hyperalgesia was induced by an intraplantar injection of carrageenan (CAR) 1% in 250 mml and PWL was measured. The results show that IC stimulation significantly increases PWL after the induction of both acute thermonociception and secondary inflammatory hyperalgesia. Also, the change in spectral measures of electrical activity in the IC consisted of increased relative power of the theta frequency band (3–7 Hz). IC increases potency in low frequencies which may correlate with a decreased nociceptive behaviour. This work highlights the role of the IC in the modulation of acute thermonociception and secondary inflammatory hyperalgesia.
S57
166 INTRATHECAL INJECTION OF A CANNABINOID CB2 RECEPTOR SELECTIVE AGONIST GW405833 BLOCKS INDUCTION OF ALLODYNIA BY SCIATIC INFLAMMATORY NEURITIS (SIN) J. Ashton1 *, P. Brownjohn1 , J. Wilkerson2 , M. Dowie3 , M. Glass3 , E. Milligan2 . 1 Department of Pharmacology & Toxicology, University of Otago., Dunedin, New Zealand; 2 Department of Neurosciences, School of Medicine, University of Mexico., Albuquerque, United States; 3 Department of Pharmacology, University of Auckland., Auckland, New Zealand Intrathecal injection of a Cannabinoid CB2 Receptor Selective Agonist GW405833 Blocks Induction of Allodynia by Sciatic Inflammatory Neuritis (SIN). Cannabinoids have been shown to ameriolate neuropathic pain through both the CB1 receptor, found on neurons and the CB2R receptor, found on immune cells in the CNS. CB2-selective agonists reduce pain after peripheral nerve injury, and CB2 activation does not cause the psychoactivity associated with CB1 activation, making CB2 agonists attractive candidates for treating neuropathic pain. However, the precise mechanism of action in the pain pathways by CB2 remains controversial. Sciatic inflammatory neuritis (SIN) lead to allodynia. We found that (intrathecal, i.t.) injection of GW405833 was efficacious in blocking the development of allodynia after SIN, assessed using von Frey filaments. However, immunohistochemical analysis using a range of polyclonal antibodies for CB2, and mRNA in situ hybridization of spinal cords failed to show any evidence of CB2 expression in the spinal cord at the acute stage of injury. Ongoing studies are aimed at evaluating the ex vivo effect of GW405833 on DRG neuron action potentials and on spinal cord G-protein activation, in order to determine the mechanism of action of GW405833 in the spinal cord in blocking the development of allodynia in SIN. 167 BEHAVIOURAL AND BIOCHEMICAL EFFECTS OF THE FATTY ACID AMIDE HYDROLASE INHIBITOR URB597 IN THE RAT FORMALIN TEST G. Ford1 *, B. Harhen2 , E. Tully1 , A. Mulcahy1 , D. Finn1 . 1 Department of Pharmacology and Therapeutics, NCBES Neuroscience Cluster and Centre for Pain Research, National University of Ireland, Galway, Galway, Ireland; 2 Centre for Bioanalytical Sciences, National University of Ireland, Galway, Galway, Ireland Fatty acid amide hydrolase (FAAH) catalyses the degradation of several endocannabinoids and fatty acid amides which are known to modulate nociception and hippocampal activity. Here, the effect of systemic administration of the FAAH inhibitor URB597 on formalinevoked nociceptive behaviour in rats was investigated. Associated changes in endocannabinoid/fatty acid amide concentrations in the ventral hippocampus and brain monoamines in regions comprising the descending inhibitory pain pathway were also determined. Intraplantar injection of formalin (50 ml 2.5% into the right hindpaw under brief 3% isoflurane anaesthesia) was used to evoke nociceptive behaviour in male Lister-Hooded rats (n = 7/group) which was scored for a 30 minute period (30–60 min postformalin). Immediately following formalin, animals received an intra-peritoneal injection of either the FAAH inhibitor URB597 (0.3 mg/kg), the cannabinoid-1 receptor antagonist rimonabant (1 mg/kg), or vehicle (ethanol:crempohor:saline). Post-mortem brain tissue monoamine levels were measured by HPLC coupled to electrochemical detection and endocannabinoid/fatty acid amide concentrations were determined by LC/MS/MS. Data were analysed by ANOVA and Tukey’s or Student-Newman-Keuls post-hoc test. URB597 significantly reduced formalin-evoked nociceptive behaviour over the entire trial, an effect accompanied by elevated levels of oleoylethanolamide and palmitoylethanolamide in the ventral hippocampus compared with vehicle-treated animals. Monoamine levels in all regions examined were not altered