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Paresthesia as a new approach of study for panic disorder: basic and clinical research

Grant number: 14/10742-7
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2014
Effective date (End): March 29, 2018
Field of knowledge:Health Sciences - Medicine - Psychiatry
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Norberto Cysne Coimbra
Grantee:Audrey Franceschi Biagioni
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):16/18218-0 - Nano-materials as a potential tool to anxiety disorder treatment: A pre-clinical study of carbon-based nano materials modulating neurogenesis and synapses in the hippocampus, BE.EP.PD


Paresthesia, a tingling sensation or numbness, is a neurological symptom that often precedes panic attacks of a serious nature. Recently, several investigations have related ventilatory changes to panic attacks. The hyperventilation syndrome, characterized by increased frequency and intensity of breaths, is often observed during panic attacks, and is present in about 40 % of patients with panic disorder. Accordingly, it was reported that the induction of panic attacks by acute hyperventilation (30 breaths / min during 4 minutes) test is a simple method of validation of diagnosis for patients with panic disorder. This test induces anxiety, feelings of fear, tremors, dizziness, crying spells and paresthesia. Nonetheless, drug therapy used to treat panic disorder, such as selective serotonin reuptake inhibitors do not appear to be effective in the control of paresthesia, because patients treated with these classes of drugs have paresthesia up to 8 months after initiation of treatment. The lack of an animal model for the study of paresthesia impedes the advancement of studies in this context . The animal model of fear-induced antinociception may be an appropriate model for the study of this symptom, because as paresthesia as fear-induced antinociception is due to the modulation of synaptic transmission between sensory neurons located in the spinal cord, through the increased activity the endogenous pain modulation system . The objective of this work is to study the analgesic effect induced hyperventilation in rats and humans, for face validity of an animal model for the study of paresthesia and propose an adjunctive treatment of panic disorder for patients with paresthesia. Thus, studies of basic and clinical research will be conducted. In basic research, a study to evaluate the analgesic effect induced by hyperventilation caused by the administration of three different doses of NMDA in ventrolateral column of the periaqueductal gray matter of rats will be performed. Besides, the effect of neurochemical lesion with local administration of ibotenic acid in the nucleus of the solitary tract of rodents to assess the involvement of this neural substrate in control of hyperventilation in defensive behavioral responses and antinociception induced by fear will be held evoked by stimulation periaqueductal gray matter of the chemical in its ventrolateral column of rats. In separate groups of animals, it will be analysed the effect of treatment with naltrexone , 2 mg/kg in animals pretreated with paroxetine (10 mg/kg) in defensive behavioral responses in hyperventilation and antinociception induced by fear evoked by chemical stimulation the ventrolateral periaqueductal gray matter of rats. In clinical research, a study will be conducted to investigate the prevalence of paresthesia induced by acute hyperventilation (30 breaths/ min for 4 minutes), in patients receiving appropriate pharmacological treatment for panic disorder. Besides, it will also be assessed the correlation between analgesic effect and the paresthesia induced acute hyperventilation in patients diagnosed with panic disorder and treated appropriately. Finally, we will assess the effect of treatment with naltrexone, 50 mg orally in a single dose, the feelings of fear, paresthesia and analgesia induced by acute hyperventilation in patients with panic disorder . (AU)

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Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE OLIVEIRA, RITHIELE CRISTINA; DE OLIVEIRA, RICARDO; FALCONI-SOBRINHO, LUIZ LUCIANO; BIAGIONI, AUDREY FRANCESCHI; ALMADA, RAFAEL CARVALHO; DOS ANJOS-GARCIA, TAYLLON; BAZAGLIA-DE-SOUSA, GUILHERME; KHAN, ASMAT ULLAH; COIMBRA, NORBERTO CYSNE. Neurotoxic lesions of the pedunculopontine tegmental nucleus impair the elaboration of postictal antinociception. Physiology & Behavior, v. 194, p. 162-169, . (11/09850-1, 14/10742-7, 08/08955-1, 09/00668-6, 13/10984-8, 12/22681-7)
ULLAH, FARHAD; DOS ANJOS-GARCIA, TAYLLON; DOS SANTOS, IEDA REGINA; BIAGIONI, AUDREY FRANCISCO; COIMBRA, NORBERTO CYSNE. Relevance of dorsomedial hypothalamus, dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal gray matter in the organization of freezing or oriented and non-oriented escape emotional behaviors. Behavioural Brain Research, v. 293, p. 143-152, . (14/10742-7, 08/08955-1, 12/03798-0, 07/01174-1)
BIAGIONI, AUDREY FRANCESCHI; DE OLIVEIRA, RITHIELE CRISTINA; DE OLIVEIRA, RICARDO; DA SILVA, JULIANA ALMEIDA; DOS ANJOS-GARCIA, TAYLION; RONCON, CAMILA MARRONI; CORRADO, ALEXANDRE PINTO; ZANGROSSI, JR., HELIO; COIMBRA, NORBERTO CYSNE. 5-Hydroxytryptamine(1A) receptors in the dorsomedial hypothalamus connected to dorsal raphe nucleus inputs modulate defensive behaviours and mediate innate fear-induced antinociception. European Neuropsychopharmacology, v. 26, n. 3, p. 532-545, . (11/09850-1, 14/10742-7, 08/08955-1, 07/01174-1, 12/03798-0, 12/23238-0)
BIAGIONI, AUDREY FRANCISCO; DOS ANJOS-GARCIA, TAYLLON; ULLAH, FARHAD; FISHER, ISAAC RENE; FALCONI-SOBRINHO, LUIZ LUCIANO; DE FREITAS, RENATO LEONARDO; FELIPPOTTI, TATIANA TOCCHINI; COIMBRA, NORBERTO CYSNE. Neuroethological validation of an experimental apparatus to evaluate oriented and non-oriented escape behaviours: Comparison between the polygonal arena with a burrow and the circular enclosure of an open-field test. Behavioural Brain Research, v. 298, n. B, p. 65-77, . (14/10742-7, 08/08955-1, 11/05821-7, 07/01174-1, 12/03798-0, 09/17258-5, 13/10984-8, 11/06036-1)
DE OLIVEIRA, RITHIELE CRISTINA; DE OLIVEIRA, RICARDO; BIAGIONI, AUDREY FRANCISCO; FALCONI-SOBRINHO, LUIZ LUCIANO; COIMBRA, NORBERTO CYSNE. Dorsal raphe nucleus acetylcholine-mediated neurotransmission modulates post-ictal antinociception: The role of muscarinic and nicotinic cholinergic receptors. Brain Research, v. 1631, p. 80-91, . (14/10742-7, 08/08955-1, 09/00668-6, 08/09897-5)
DA SILVA, JULIANA ALMEIDA; BIAGIONI, AUDREY FRANCISCO; ALMADA, RAFAEL CARVALHO; DE SOUZA CRIPPA, JOSE ALEXANDRE; CECILIO HALLAK, JAIME EDUARDO; ZUARDI, ANTONIO WALDO; COIMBRA, NORBERTO CYSNE. Dissociation between the panicolytic effect of cannabidiol microinjected into the substantia nigra, pars reticulata, and fear-induced antinociception elicited by bicuculline administration in deep layers of the superior colliculus: The role of CB1-cannabinoid receptor in the ventral mesencephalon. European Journal of Pharmacology, v. 758, p. 153-163, . (09/02458-9, 14/10742-7, 09/54014-7, 10/15140-4, 12/03798-0, 07/01174-1, 12/22681-7)
DA SILVA, JULIANA ALMEIDA; BIAGIONI, AUDREY FRANCESCHI; ALMADA, RAFAEL CARVALHO; DE FREITAS, RENATO LEONARDO; COIMBRA, NORBERTO CYSNE. Panicolytic-like effects caused by substantia nigra pars reticulata pretreatment with low doses of endomorphin-1 and high doses of CTOP or the NOP receptors antagonist JTC-801 in male Rattus norvegicus. Psychopharmacology, v. 234, n. 20, p. 3009-3025, . (14/11869-0, 09/02458-9, 14/10742-7, 17/11855-8, 12/03798-0, 09/54014-7, 10/15140-4, 13/12916-0, 09/17258-5, 07/01174-1, 15/10313-1, 12/22681-7)

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