- Email: [email protected]
F107 THE GATE THEORY OF PAIN REVISITED: INTRINSIC AND SYNAPTIC PLASTICITY IN A NOVEL NEUROCOMPUTATIONAL MODEL
POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
stronger BOLD-reductions were associated with stronger behavioral pain reductions (t(14) = 2.27, P = 0.02).
Fig. 1.
Conclusions: Our data reveal that one mechanism behind reduced pain perception during distraction is control of incoming nociceptive information already at the level of the spinal cord. Disclosure: None declared
F107 THE GATE THEORY OF PAIN REVISITED: INTRINSIC AND SYNAPTIC PLASTICITY IN A NOVEL NEUROCOMPUTATIONAL MODEL J. Ropero Pelaez1 , S. Taniguchi2 *. 1 Center of Mathematics, Computation and Cognition, Federal University of ABC, 2 Basics Sciences, Albert Einstein Hospital, S˜ ao Paulo, Brazil Background and Aims: In this paper, the gate theory of pain is revisited with a neurocomputational simulation that uses synaptic and intrinsic plasticity. The “gate theory” circuit becomes a learning system that adapts its parameters according to incoming nociceptive and sensory patterns. Methods: A computational model of the basic “gate circuit” was implemented in Matlab programming language. Rate-code neuron’s were used with strictly excitatory afferences. Grossberg’s presynaptic rule was used for modeling NMDA synaptic plasticity. An iterative equation was developed for modeling intrinsic plasticity. Nociceptive signal to the “gate circuit” were modeled as weaker inputs when compared to stronger sensory inputs arriving through myelinated axons. Results: Our hipothesis is that conventional sets of sensory and nociceptive patterns train the “gate circuit” for behaving in a conventional way, i.e., the gate closes the passage of pain if sensory and nociceptive stimuli appear together, whereas, with other stimuli combination, pain is allowed to freely pass through the gate. Our simulations show that the conventional behavior of the “gate circuit” is only achieved if both synaptic and intrinsic plasticity are considered. When these two types of plasticity are used together, synaptic weights and neuron’s firing-thresholds always converge to the same final values with independence of the initial setup of synaptic weights and neuron’s firing thresholds. Conclusions: The “gate theory of pain” proper functioning was obtained in the model when synaptic and intrinsic plasticity are considered. Disclosure: None declared
F108 CEREBROLYSIN ATTENUATES BLOOD–SPINAL CORD BARRIER DISRUPTION, ASTROCYTIC ACTIVATION AND NEURONAL DAMAGE IN THE RAT SPINAL CORD FOLLOWING FORMALIN NOCICEPTION H.S. Sharma1 *, R. Patnaik2 , A. Sharma1 , D.F. Muresanu3 . 1 Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden; 2 School of Biomedical Engineering, Inst Technology, Banaras Hindu University, Varanasi, India; 3 Neurology, University of Medicine & Pharmacy, Cluj-Napoca, Romania Background and Aims: Formalin administration in the hind-paw results in allodynia and hyperalgesia causing upregulation of spinal
105
cord microglial activity. However, whether formalin allodynia also disrupts blood-spinal cord barrier (BSCB) leading to neuronal or astrocytic dysfunction in the cord is unknown. Furthermore, it is not known whether exogenous supplement of neurotrophic factors could restore some of these pathological changes following formalin nociception. Methods: Rats were administered 50 ml (4%) formalin (s.c.) or saline into the planter surface of their right hind paw. Separate group of animals received Cerebrolysin (Ever NeuroPharma, Austria, 2.5 ml/kg or 5 ml/kg, i.v. a mixture of several neurotrophic factors and peptides) once on day 2, 4, and 6 after formalin injection. On the day 2, 4, 6, 8, 10 and 12, leakage of serum albumin and activation of astrocytes was examined using albumin and glial fibrillary acidic protein (GFAP) immunoreactivity in the cord. Neuronal damage was investigates by Nissl staining. Results: Pronounced leakage of serum albumin and upregulation of GFAP were seen in the spinal cord following 4 to 6 days reaching a peak value on the 10th day. Neuronal distortion and damage correlates well with the albumin immunoreactivity. Cerebrolysin treatment significantly attenuated albumin leakage, GFAP activation and neuronal damages in a dose related manner. Conclusions: These observations are the first to show that disruption of the BSCB is crucial in formalin induced spinal cord astrocytic activity and neuronal damage. Furthermore, cerebrolysin treatment could result in pronounced neuroprotection against BSCB disruption, astrocytic activation and cord pathology against formalin nociception. Disclosure: None declared
F109 THE ROLE OF BETA 1 AND BETA 2 ADRENORECEPTOR IN ACUTE PAIN MODULATION P. Lamothe Molina1,2,3 *, A. Melo-Carrillo1,2,3 , A. Castillo Tovar1,3 , A. Lopez-Avila4,5 . 1 Laboratorio de Neurofisiologia de la Percepcion, Instituto Nacional de Psiquiatria Ramon de la Fuente Mu˜ niz, 2 Universidad Nacional Autonoma de Mexico, 3 Universidad La Salle, 4 Laboratorio de Neurofisiologia de la Percepcion, Instituto Nacional de Psiquiatr´ıa Ram´ on de la Fuente Mu˜ niz, 5 Universidad Autonoma Metropolitana. Xochimilco, Mexico, Mexico The role of adrenergic receptors in pain modulation is not fully understood. Intrathecal clonidine, an a2-adrenoceptor agonist, is used as an adjuvant treatment in oncological pain. Recent studies have found that the b2-adrenoceptor is involved in the analgesic effect of dual serotonin/norepinephrine inhibitory reuptakers. Also, non-selective b-adrenergic receptor antagonists are used to treat fibromyalgia. The aim of this investigation was to determine the role of b1 and b2 adrenergic receptors in acute pain. Male Wistar rats (250–350 g) were used. A stereotaxic guided L2-L3 laminectomy was performed. The receptive field of the right hind paw was found descending the electrode from the meningeal tissue to a maximum depth of 500mm. Basal frequency of depolarization, and that induced by non-painful (Non-P) mechanical stimulus or painful (P) mechanical stimulus, was registered before and after drug administration. Groups: 1. Saline 0.9%, 2. Epinephrine 100 mg, 3. Metoprolol (b1adrenoceptor-antagonist) 10 mg, 4. Clenbuterol (b2adrenoceptor agonist) (100 mg). All drugs were administered topically on the spinal cord. Results: The frequency of depolarization evoked by P-stimuli was less after epinephrine (57% less, p < 0.01) and metoprolol (47% less, p < 0.001) administration, than before. There was no significant difference in the frequency of depolarization evoked by P-stimuli neither in the saline nor the clenbuterol group. These results show that the non-specific adrenergic agonism as well as the specific b1adrenoceptor antagonism produces an analgesic effect. We didn’t
stronger BOLD-reductions were associated with stronger behavioral pain reductions (t(14) = 2.27, P = 0.02).
Fig. 1.
Conclusions: Our data reveal that one mechanism behind reduced pain perception during distraction is control of incoming nociceptive information already at the level of the spinal cord. Disclosure: None declared
F107 THE GATE THEORY OF PAIN REVISITED: INTRINSIC AND SYNAPTIC PLASTICITY IN A NOVEL NEUROCOMPUTATIONAL MODEL J. Ropero Pelaez1 , S. Taniguchi2 *. 1 Center of Mathematics, Computation and Cognition, Federal University of ABC, 2 Basics Sciences, Albert Einstein Hospital, S˜ ao Paulo, Brazil Background and Aims: In this paper, the gate theory of pain is revisited with a neurocomputational simulation that uses synaptic and intrinsic plasticity. The “gate theory” circuit becomes a learning system that adapts its parameters according to incoming nociceptive and sensory patterns. Methods: A computational model of the basic “gate circuit” was implemented in Matlab programming language. Rate-code neuron’s were used with strictly excitatory afferences. Grossberg’s presynaptic rule was used for modeling NMDA synaptic plasticity. An iterative equation was developed for modeling intrinsic plasticity. Nociceptive signal to the “gate circuit” were modeled as weaker inputs when compared to stronger sensory inputs arriving through myelinated axons. Results: Our hipothesis is that conventional sets of sensory and nociceptive patterns train the “gate circuit” for behaving in a conventional way, i.e., the gate closes the passage of pain if sensory and nociceptive stimuli appear together, whereas, with other stimuli combination, pain is allowed to freely pass through the gate. Our simulations show that the conventional behavior of the “gate circuit” is only achieved if both synaptic and intrinsic plasticity are considered. When these two types of plasticity are used together, synaptic weights and neuron’s firing-thresholds always converge to the same final values with independence of the initial setup of synaptic weights and neuron’s firing thresholds. Conclusions: The “gate theory of pain” proper functioning was obtained in the model when synaptic and intrinsic plasticity are considered. Disclosure: None declared
F108 CEREBROLYSIN ATTENUATES BLOOD–SPINAL CORD BARRIER DISRUPTION, ASTROCYTIC ACTIVATION AND NEURONAL DAMAGE IN THE RAT SPINAL CORD FOLLOWING FORMALIN NOCICEPTION H.S. Sharma1 *, R. Patnaik2 , A. Sharma1 , D.F. Muresanu3 . 1 Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden; 2 School of Biomedical Engineering, Inst Technology, Banaras Hindu University, Varanasi, India; 3 Neurology, University of Medicine & Pharmacy, Cluj-Napoca, Romania Background and Aims: Formalin administration in the hind-paw results in allodynia and hyperalgesia causing upregulation of spinal
105
cord microglial activity. However, whether formalin allodynia also disrupts blood-spinal cord barrier (BSCB) leading to neuronal or astrocytic dysfunction in the cord is unknown. Furthermore, it is not known whether exogenous supplement of neurotrophic factors could restore some of these pathological changes following formalin nociception. Methods: Rats were administered 50 ml (4%) formalin (s.c.) or saline into the planter surface of their right hind paw. Separate group of animals received Cerebrolysin (Ever NeuroPharma, Austria, 2.5 ml/kg or 5 ml/kg, i.v. a mixture of several neurotrophic factors and peptides) once on day 2, 4, and 6 after formalin injection. On the day 2, 4, 6, 8, 10 and 12, leakage of serum albumin and activation of astrocytes was examined using albumin and glial fibrillary acidic protein (GFAP) immunoreactivity in the cord. Neuronal damage was investigates by Nissl staining. Results: Pronounced leakage of serum albumin and upregulation of GFAP were seen in the spinal cord following 4 to 6 days reaching a peak value on the 10th day. Neuronal distortion and damage correlates well with the albumin immunoreactivity. Cerebrolysin treatment significantly attenuated albumin leakage, GFAP activation and neuronal damages in a dose related manner. Conclusions: These observations are the first to show that disruption of the BSCB is crucial in formalin induced spinal cord astrocytic activity and neuronal damage. Furthermore, cerebrolysin treatment could result in pronounced neuroprotection against BSCB disruption, astrocytic activation and cord pathology against formalin nociception. Disclosure: None declared
F109 THE ROLE OF BETA 1 AND BETA 2 ADRENORECEPTOR IN ACUTE PAIN MODULATION P. Lamothe Molina1,2,3 *, A. Melo-Carrillo1,2,3 , A. Castillo Tovar1,3 , A. Lopez-Avila4,5 . 1 Laboratorio de Neurofisiologia de la Percepcion, Instituto Nacional de Psiquiatria Ramon de la Fuente Mu˜ niz, 2 Universidad Nacional Autonoma de Mexico, 3 Universidad La Salle, 4 Laboratorio de Neurofisiologia de la Percepcion, Instituto Nacional de Psiquiatr´ıa Ram´ on de la Fuente Mu˜ niz, 5 Universidad Autonoma Metropolitana. Xochimilco, Mexico, Mexico The role of adrenergic receptors in pain modulation is not fully understood. Intrathecal clonidine, an a2-adrenoceptor agonist, is used as an adjuvant treatment in oncological pain. Recent studies have found that the b2-adrenoceptor is involved in the analgesic effect of dual serotonin/norepinephrine inhibitory reuptakers. Also, non-selective b-adrenergic receptor antagonists are used to treat fibromyalgia. The aim of this investigation was to determine the role of b1 and b2 adrenergic receptors in acute pain. Male Wistar rats (250–350 g) were used. A stereotaxic guided L2-L3 laminectomy was performed. The receptive field of the right hind paw was found descending the electrode from the meningeal tissue to a maximum depth of 500mm. Basal frequency of depolarization, and that induced by non-painful (Non-P) mechanical stimulus or painful (P) mechanical stimulus, was registered before and after drug administration. Groups: 1. Saline 0.9%, 2. Epinephrine 100 mg, 3. Metoprolol (b1adrenoceptor-antagonist) 10 mg, 4. Clenbuterol (b2adrenoceptor agonist) (100 mg). All drugs were administered topically on the spinal cord. Results: The frequency of depolarization evoked by P-stimuli was less after epinephrine (57% less, p < 0.01) and metoprolol (47% less, p < 0.001) administration, than before. There was no significant difference in the frequency of depolarization evoked by P-stimuli neither in the saline nor the clenbuterol group. These results show that the non-specific adrenergic agonism as well as the specific b1adrenoceptor antagonism produces an analgesic effect. We didn’t