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

Abstract

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)