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1.
Brain Res ; 1844: 149134, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39097217

RESUMEN

RATIONALE: The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is a key structure in panic. OBJECTIVES: To evaluate the role of nitric oxide (NO) in defensive behaviour and antinociception. METHODS: Either Nω-propyl-L-arginine (NPLA) or Carboxy-PTIO was microinjected in the PrL cortex, followed by hypothalamic treatment with bicuculline. The exploratory behaviours, defensive reactions and defensive antinociception were recorded. Encephalic c-Fos protein was immunolabelled after escape behaviour. RESULTS: NPLA (an inhibition of nNOs) decreased panic-like responses and innate fear-induced antinociception. The c-PTIO (a membrane-impermeable NO scavenger) decreased the escape behaviour. PrL cortex pre-treatment with c-PTIO at all doses decreased defensive antinociception. c-Fos protein was labelled in neocortical areas, limbic system, and mesencephalic structures. CONCLUSION: The NPLA and c-PTIO in the PrL/mPFC decreased the escape behaviour and defensive antinociception organised by medial hypothalamic nuclei. The oriented escape behaviour recruits neocortical areas, limbic system, and mesencephalic structures. These findings suggest that the organisation of defensive antinociception recruits NO-signalling mechanisms within the PrL cortex. Furthermore, the present findings also support the role of NO as a retrograde messenger in the PrL cortex during panic-like emotional reactions.


Asunto(s)
Óxido Nítrico , Pánico , Corteza Prefrontal , Proteínas Proto-Oncogénicas c-fos , Ratas Wistar , Animales , Masculino , Óxido Nítrico/metabolismo , Pánico/fisiología , Pánico/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Corteza Prefrontal/metabolismo , Corteza Prefrontal/fisiología , Corteza Prefrontal/efectos de los fármacos , Arginina/farmacología , Arginina/análogos & derivados , Transducción de Señal/fisiología , Transducción de Señal/efectos de los fármacos , Reacción de Fuga/fisiología , Reacción de Fuga/efectos de los fármacos , Bicuculina/farmacología , Benzoatos , Imidazoles
2.
Methods Mol Biol ; 2831: 351-375, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39134862

RESUMEN

Fluorescent and non-fluorescent neural tract tracers enable the investigation of neural pathways in both peripheral and central nervous systems in laboratory animals demonstrating images with high resolution and great anatomic precision. Anterograde and retrograde viral tracers are important cutting-edge tools for neuroanatomical mapping. The optogenetic consists of an advanced alternative for in vivo neural tract tracing procedures, fundamentally considering the possibility to dissect and modulate pathways either exciting or inhibiting neural circuits in laboratory animals. The neurotractography by diffusion tensor imaging in vivo procedures enables the study of neural pathways in humans with reasonable accuracy. Here we describe the procedure of classical anatomic neural tract tracing and modern optogenetic technique performed in anima vili in addition to different diffusion tensor neurotractography performed in anima nobili.


Asunto(s)
Imagen de Difusión Tensora , Optogenética , Optogenética/métodos , Animales , Imagen de Difusión Tensora/métodos , Técnicas de Trazados de Vías Neuroanatómicas/métodos , Vías Nerviosas , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Encéfalo/metabolismo , Trazadores del Tracto Neuronal , Humanos , Ratones
3.
Artículo en Inglés | MEDLINE | ID: mdl-38797491

RESUMEN

BACKGROUND AND PURPOSE: Chronic neuropathic pain (NP) is commonly associated with cognitive and emotional impairments. Cannabidiol (CBD) presents a broad spectrum of action with a potential analgesic effect. This work investigates the CBD effect on comorbidity between chronic NP, depression, and memory impairment. EXPERIMENTAL APPROACH: The connection between the neocortex and the hippocampus was investigated with biotinylated dextran amine (BDA) deposits in the prelimbic cortex (PrL). Wistar rats were submitted to chronic constriction injury (CCI) of the sciatic nerve and CA1 treatment with CBD (15, 30, 60 nmol). KEY RESULTS: BDA-labeled perikarya and terminal buttons were found in CA1 and dentate gyrus. CCI-induced mechanical and cold allodynia increased c-Fos protein expression in the PrL and CA1. The number of astrocytes in PrL and CA1 increased, and the number of neuroblasts decreased in CA1. Animals submitted to CCI procedure showed increasing depressive-like behaviors, such as memory impairment. CBD (60 nmol) treatment decreased mechanical and cold allodynia, attenuated depressive-associated behaviors, and improved memory performance. Cobalt chloride (CoCl2: 1 nM), WAY-100635 (0.37 nmol), and AM251 (100 nmol) intra-PrL reversed the effect of CA1 treatment with CBD (60 nmol) on nociceptive, cognitive, and depressive behaviors. CONCLUSION: CBD represents a promising therapeutic perspective in the pharmacological treatment of chronic NP and associated comorbidities such as depression and memory impairments. The CBD effects possibly recruit the CA1-PrL pathway, inducing neuroplasticity. CBD acute treatment into the CA1 produces functional and molecular morphological improvements.


Asunto(s)
Cannabidiol , Disfunción Cognitiva , Hipocampo , Neocórtex , Neuralgia , Ratas Wistar , Animales , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , Masculino , Neuralgia/tratamiento farmacológico , Ratas , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Neocórtex/efectos de los fármacos , Hiperalgesia/tratamiento farmacológico , Vías Nerviosas/efectos de los fármacos , Síntomas Afectivos/tratamiento farmacológico , Síntomas Afectivos/etiología
4.
Neurosci Lett ; 820: 137572, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38072029

RESUMEN

BACKGROUND: Haloperidol (HAL) is an antipsychotic used in the treatment of schizophrenia. However, adverse effects are observed in the extrapyramidal tracts due to its systemic action. Natural compounds are among the treatment alternatives widely available in Brazilian biodiversity. Mygalin (MY), a polyamine that was synthesized from a natural molecule present in the hemolymph of the Acanthoscurria gomesian spider, may present an interesting approach. AIMS: This study aimed to evaluate the effect of MY in mice subjected to HAL-induced catalepsy. METHODS: Male Swiss mice were used. Catalepsy was induced by intraperitoneal administration of HAL (0.5 mg/kg - 1 mL/Kg) diluted in physiological saline. To assess the MY effects on catalepsy, mice were assigned to 4 groups: (1) physiological saline (NaCl 0.9 %); (2) MY at 0.002 mg/Kg; (3) MY at 0.02 mg/Kg; (4) MY at 0.2 mg/Kg. MY or saline was administered intraperitoneally (IP) 10 min b HAL before saline. Catalepsy was evaluated using the bar test at 15, 30, 60, 90, and 120 min after the IP administration of HAL. RESULTS: The latency time in the bar test 15, 30, 60, and 90 min increased (p < 0.05) after IP administration of HAL compared to the control group. Catalepsy was attenuated 15, 30, 90, and 120 min (p < 0.05) after the IP-administration of MY at 0.2 mg/Kg; while MY at 0.02 mg/Kg attenuated catalepsy 15 min after the HAL treatment. Our findings showed that MY attenuates the HAL-induced cataleptic state in mice.


Asunto(s)
Antipsicóticos , Arañas , Ratones , Masculino , Animales , Haloperidol/farmacología , Catalepsia/inducido químicamente , Catalepsia/tratamiento farmacológico , Antipsicóticos/efectos adversos
5.
Neurosci Lett, v. 820, 137572, jan. 2024
Artículo en Inglés | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5222

RESUMEN

Background: Haloperidol (HAL) is an antipsychotic used in the treatment of schizophrenia. However, adverse effects are observed in the extrapyramidal tracts due to its systemic action. Natural compounds are among the treatment alternatives widely available in Brazilian biodiversity. Mygalin (MY), a polyamine that was synthesized from a natural molecule present in the hemolymph of the Acanthoscurria gomesian spider, may present an interesting approach. Aims: This study aimed to evaluate the effect of MY in mice subjected to HAL-induced catalepsy. Methods: Male Swiss mice were used. Catalepsy was induced by intraperitoneal administration of HAL (0.5 mg/kg − 1 mL/Kg) diluted in physiological saline. To assess the MY effects on catalepsy, mice were assigned to 4 groups: (1) physiological saline (NaCl 0.9 %); (2) MY at 0.002 mg/Kg; (3) MY at 0.02 mg/Kg; (4) MY at 0.2 mg/Kg. MY or saline was administered intraperitoneally (IP) 10 min b HAL before saline. Catalepsy was evaluated using the bar test at 15, 30, 60, 90, and 120 min after the IP administration of HAL. Results: The latency time in the bar test 15, 30, 60, and 90 min increased (p < 0.05) after IP administration of HAL compared to the control group. Catalepsy was attenuated 15, 30, 90, and 120 min (p < 0.05) after the IP-administration of MY at 0.2 mg/Kg; while MY at 0.02 mg/Kg attenuated catalepsy 15 min after the HAL treatment. Our findings showed that MY attenuates the HAL-induced cataleptic state in mice.

7.
Exp Brain Res ; 241(11-12): 2591-2604, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37725136

RESUMEN

Neuropathic pain (NP) represents a complex disorder with sensory, cognitive, and emotional symptoms. The medial prefrontal cortex (mPFC) takes critical regulatory roles and may change functionally and morphologically during chronic NP. There needs to be a complete understanding of the neurophysiological and psychopharmacological bases of the NP phenomenon. This study aimed to investigate the participation of the infralimbic division (IFL) of the mPFC in chronic NP, as well as the role of the N-methyl-D-aspartic acid receptor (NMDAr) in the elaboration of chronic NP. Male Wistar rats were submitted to the von Frey and acetone tests to assess mechanical and cold allodynia after 21 days of chronic constriction injury (CCI) of the sciatic nerve or Sham-procedure ("false operated"). Electrical neurostimulation of the IFL/mPFC was performed by low-frequency stimuli (20 µA, 100 Hz) applied for 15 s by deep brain stimulation (DBS) device 21 days after CCI. Either cobalt chloride (CoCl2 at 1.0 mM/200 nL), NMDAr agonist (at 0.25, 1.0, and 2.0 nmol/200 nL) or physiological saline (200 nL) was administered into the IFL/mPFC. CoCl2 administration in the IFL cortex did not alter either mechanical or cold allodynia. DBS stimulation of the IFL cortex decreased mechanical allodynia in CCI rats. Chemical stimulation of the IFL cortex by an NMDA agonist (at 2.0 nmol) decreased mechanical allodynia. NMDA at any dose (0.25, 1.0, and 2.0 nmol) reduced the flicking/licking duration in the cold test. These findings suggest that the IFL/mPFC and the NMDAr of the neocortex are involved in attenuating chronic NP in rats.


Asunto(s)
Hiperalgesia , Neuralgia , Ratas , Masculino , Animales , N-Metilaspartato/farmacología , Dimensión del Dolor , Ratas Wistar , Neuralgia/terapia , Receptores de N-Metil-D-Aspartato/metabolismo , Corteza Prefrontal/metabolismo
8.
J Biochem Mol Toxicol ; 37(7): e23353, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37069807

RESUMEN

Depression has a high rate of comorbidity with neuropathic pain. This study aims to investigate the effect of Mygalin, an acylpolyamine synthesized from a natural molecule in the hemolymph of the Acanthoscurria gomesiana spider, injected into the prelimbic (PrL) region of the medial prefrontal cortex on chronic neuropathic pain and depression comorbidity in rats. To investigate that comorbidity, neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in male Wistar rats. The biotinylated biodextran amine (BDA) bidirectional neural tract tracer was microinjected into the PrL cortex to study brain connections. Rodents were further subjected to von Frey (mechanical allodynia), acetone (cold allodynia), and forced swim (depressive-like behavior) tests. BDA neural tract tracer-labeled perikarya were found in the dorsal columns of the periaqueductal gray matter (dPAG) and the dorsal raphe nucleus (DRN). Neuronal activity of DRN neurons decreased in CCI rats. However, PrL cortex treatment with Mygalin increased the number of spikes on DRN neurons. Mygalin treatment in the PrL cortex decreased both mechanical and cold allodynia and immobility behavior in CCI rats. PrL cortex treatment with N-methyl-D-aspartate (NMDA) receptor receptors attenuated the analgesic and antidepressive effects caused by Mygalin. The PrL cortex is connected with the dPAG and DRN, and Mygalin administration into the PrL increased the activity of DRN neurons. Mygalin in the PrL cortex produced antinociceptive and antidepressive-like effects, and the NMDA agonist reversed these effects.


Asunto(s)
Neuralgia , Arañas , Ratas , Masculino , Animales , Depresión , Hiperalgesia , N-Metilaspartato/farmacología , Ratas Wistar , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Receptores de N-Metil-D-Aspartato , Comorbilidad , Corteza Prefrontal
9.
Neuromodulation ; 26(8): 1622-1636, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36057495

RESUMEN

BACKGROUND AND AIMS: The dysgranula parts of the posterior insular cortex (PIC) stimulation (PICS) has been investigated as a new putative cortical target for nonpharmacologic therapies in patients with chronic and neuropathic pain (NP). This work investigates the neural bases of insula neurostimulation-induced antinociception and glutamatergic neurochemical mechanisms recruited by the PICS in animals with neuropathy. MATERIALS AND METHODS: Male Wistar rats were submitted to the von Frey and acetone tests to assess mechanical and cold allodynia after 21 days of chronic constriction injury (CCI) of the sciatic nerve or Sham procedure ("false operated"). Either the Cascade Blue 3000 MW lysine-fixable dextran (CBD) or the biotinylated dextran amine 3000 MW (BDA) neural tract tracer was microinjected into the PIC. The electrical PICS was performed at a low frequency (20 µA, 100 Hz) for 15 seconds by a deep brain stimulation device. PIC N-methyl-D-aspartate (NMDA) receptors (NMDAR) blockade with the selective antagonist LY235959 (at 2, 4, and 8 nmol/200 nL) followed by PICS was investigated in rats with CCI. RESULTS: PIC sends projections to the caudal pontine reticular nucleus, alpha part of the parvicellular reticular nucleus, dorsomedial tegmental area, and secondary somatosensory cortex (S2). PICS decreased both mechanical and cold allodynia in rats with chronic NP. Blockade of NMDAR in the PIC with LY235959 at 8 nmol attenuated PICS-produced antinociception. CONCLUSION: Neuroanatomic projections from the PIC to pontine reticular nuclei and S2 may contribute to chronic NP signaling. PICS attenuates the chronic NP, and the NMDA glutamatergic system in the PIC may be involved in PICS-induced antinociception in rodents with NP conditions.


Asunto(s)
N-Metilaspartato , Neuralgia , Humanos , Ratas , Masculino , Animales , N-Metilaspartato/uso terapéutico , Hiperalgesia/terapia , Corteza Insular , Ratas Wistar , Neuralgia/tratamiento farmacológico , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/uso terapéutico
10.
J Biochem Mol Toxicol, v. 37, n. 7, e23353, jul. 2023
Artículo en Inglés | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-4968

RESUMEN

Depression has a high rate of comorbidity with neuropathic pain. This study aims to investigate the effect of Mygalin, an acylpolyamine synthesized from a natural molecule in the hemolymph of the Acanthoscurria gomesiana spider, injected into the prelimbic (PrL) region of the medial prefrontal cortex on chronic neuropathic pain and depression comorbidity in rats. To investigate that comorbidity, neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in male Wistar rats. The biotinylated biodextran amine (BDA) bidirectional neural tract tracer was microinjected into the PrL cortex to study brain connections. Rodents were further subjected to von Frey (mechanical allodynia), acetone (cold allodynia), and forced swim (depressive-like behavior) tests. BDA neural tract tracer-labeled perikarya were found in the dorsal columns of the periaqueductal gray matter (dPAG) and the dorsal raphe nucleus (DRN). Neuronal activity of DRN neurons decreased in CCI rats. However, PrL cortex treatment with Mygalin increased the number of spikes on DRN neurons. Mygalin treatment in the PrL cortex decreased both mechanical and cold allodynia and immobility behavior in CCI rats. PrL cortex treatment with N-methyl-D-aspartate (NMDA) receptor receptors attenuated the analgesic and antidepressive effects caused by Mygalin. The PrL cortex is connected with the dPAG and DRN, and Mygalin administration into the PrL increased the activity of DRN neurons. Mygalin in the PrL cortex produced antinociceptive and antidepressive-like effects, and the NMDA agonist reversed these effects.

11.
Behav Brain Res ; 415: 113522, 2021 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-34391797

RESUMEN

BACKGROUND: Motor cortex stimulation (MCS) is proper as a non-pharmacological therapy for patients with chronic and neuropathic pain (NP). AIMS: This work aims to investigate if the MCS in the primary motor cortex (M1) produces analgesia and how the MCS could interfere in the MCS-induced analgesia. Also, to elucidate if the persistent activation of N-methyl-d-aspartic acid receptor (NMDAr) in the periaqueductal grey matter (PAG) can contribute to central sensitisation of the NP. METHODS: Male Wistar rats were submitted to the von Frey test to evaluate the mechanical allodynia after 21 days of chronic constriction injury (CCI) of the sciatic nerve. The MCS was performed with low-frequency (20 µA, 100 Hz) currents during 15 s by a deep brain stimulation (DBS) device. Moreover, the effect of M1-treatment with an NMDAr agonist (at 2, 4, and 8 nmol) was investigated in CCI rats. The PAG dorsomedial column (dmPAG) was pretreated with the NMDAr antagonist LY 235959 (at 8 nmol), followed by MCS. RESULTS: The MCS decreased the mechanical allodynia in rats with chronic NP. The M1-treatment with an NMDA agonist at 2 and 8 nmol reduced the mechanical allodynia in CCI rats. In addition, dmPAG-pretreatment with LY 235959 at 8 nmol attenuated the mechanical allodynia evoked by MCS. CONCLUSION: The M1 cortex glutamatergic system is involved in the modulation of chronic NP. The analgesic effect of MCS may depend on glutamate signaling recruitting NMDAr located on PAG neurons in rodents with chronic NP.


Asunto(s)
Dolor Crónico/terapia , Estimulación Encefálica Profunda , Agonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Corteza Motora/efectos de los fármacos , Neuralgia/terapia , Sustancia Gris Periacueductal/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/fisiología , Analgesia , Animales , Modelos Animales de Enfermedad , Isoquinolinas/farmacología , Masculino , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores
12.
Pain Med ; 22(2): 338-351, 2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-32875331

RESUMEN

BACKGROUND: Chronic constriction injury (CCI) is a model of neuropathic pain induced by four loose ligatures around the sciatic nerve. This work aimed to investigate the sensory, affective, cognitive, and motor changes induced by an adaptation of the CCI model by applying a single ligature around the sciatic nerve. METHODS: Mechanical allodynia was measured from day 1 to day 28 postsurgery by the von Frey test. The beam walking test (BWT) was conducted weekly until 28 days after surgery. Anxiety- and depression-like behaviors, and cognitive performance were assessed through the open field (OF), forced swimming (FS), and novel object recognition (NOR) tests, respectively, 21 days after surgery. RESULTS: The two CCI models, both Bennett and Xie's model (four ligatures of the sciatic nerve) and a modification of it (one ligature), induced mechanical allodynia, increased immobility in the FS, and reduced recognition index in the NOR. The exploratory behavior and time spent in the central part of the arena decreased, while the defensive behavior increased in the OF. The animals subjected to the two CCI models showed motor alterations in the BWT; however, autotomy was observed only in the group with four ligatures and not in the group with a single ligature. CONCLUSIONS: Overall these results demonstrate that our adapted CCI model, using a single ligature around the sciatic nerve, induces sensory, affective, cognitive, and motor alterations comparable to the CCI model with four ligatures without generating autotomy. This adaptation to the CCI model may therefore represent an appropriate and more easily performed model for inducing neuropathic pain and study underlying mechanisms and effective treatments.


Asunto(s)
Disfunción Cognitiva , Mononeuropatías , Neuralgia , Animales , Constricción , Modelos Animales de Enfermedad , Hiperalgesia/epidemiología , Neuralgia/epidemiología , Neuralgia/etiología , Ratas , Nervio Ciático
13.
Psicol. pesq ; 14(3): 66-82, dez. 2020. ilus
Artículo en Portugués | LILACS-Express | LILACS, Index Psicología - Revistas | ID: biblio-1149495

RESUMEN

Dor é uma experiência pessoal e subjetiva que pode apenas ser sentida pelo sofredor. A dor aguda tem a finalidade de avisar o indivíduo que algo está errado. Contudo, a dor crônica (DC) é um problema global de saúde, que afeta a qualidade de vida e torna o indivíduo parcial ou totalmente incapacitado. A pesquisa básica utiliza diversos modelos animais para o estudo da dor aguda ou crônica, bem como para o estudo das principais comorbidades oriundas de sua cronificação como a ansiedade e a depressão. Esta revisão aborda os modelos animais mais comumente utilizados neste contexto.


Pain is a personal and subjective experience that can only be felt by the sufferer. Acute pain is intended to warn the individual that something is wrong. However, chronic pain (CP) is a global health problem, affecting the quality of life and making the individual parts or disabled. Basic research uses several animal models for the study of acute or chronic pain, as well as for the study of the main comorbidities arising from their chronicity, such as anxiety and depression. This review focuses on the animal models most commonly used in this context.


El dolor es una experiencia personal y subjetiva que solo puede sentir la víctima. El dolor agudo está destinado a advertir al individuo que algo está mal. Sin embargo, el dolor crónico (EC) es un problema de salud global, que afecta la calidad de vida y hace que el individuo esté parcial o totalmente discapacitado. La investigación básica utiliza varios modelos animales para el estudio del dolor agudo o crónico, así como para el estudio de las principales comorbilidades resultantes de su cronicidad, como la ansiedad y la depresión. Esta revisión se centra en los modelos animales más utilizados en este contexto.

14.
SciELO Preprints; nov. 2020.
Preprint en Portugués | SciELO Preprints | ID: pps-1414

RESUMEN

BACKGROUND AND OBJECTIVES: The International Association for the Study of Pain recommends revising the definition of pain to "An unpleasant sensory and emotional experience associated with, or similar to that associated with actual or potential tissue damage." In fact, pain is a personal experience influenced to varying degrees by biological, psychological and social factors.1 The pandemic caused by (SARS-CoV-2) exposed health professionals who were not prepared for the unprecedented challenges. Many focused on ventilators, intensive care beds, but others will remain at the forefront of pain management. The aim of this paper was to present a review of the impact of the COVID-19 pandemic on pain management, in addition to proposing an alternative to the present context, such as telerehabilitation. CONTENTS: This is an integrative review carried out on the databases: LILACS, Scielo, Pubmed, Scopus, Web of Science, PubCovid and databases dedicated to the publication of Preprints on the COVID-19 theme, such as Psyarxiv and Preprint MedRxiv. In this review we intend to highlight the cognitive, emotional and behavioral impairments related to pain during a pandemic caused by COVID-19. CONCLUSION: The pandemic context and social isolation can negatively interfere in the sensitivity responses and in the treatment of pain, either by the increase in pain events in the population, impacted by social and psychological losses or by the interruption of face-to-face care during a pandemic. At this point, we recommend a gradual advance in addressing current treatment today and propose a future roadmap to face challenges that may arise.


JUSTIFICATIVA E OBJETIVOS: A Associação Internacional para o Estudo da Dor recomendou a revisão da definição de dor para "Uma experiência sensorial e emocional desagradável associada com, ou semelhante àquela associada a dano real ou potencial do tecido". De fato, a dor é uma experiência pessoal influenciada em vários graus por fatores biológicos, psicológicos e sociais1. A pandemia provocada pela (SARS-CoV-2) expôs profissionais de saúde que não estavam preparados para os desafios sem precedentes. Muitos se concentraram em ventiladores, leitos de terapia intensiva, mas outros permaneceram na vanguarda do tratamento da dor. O objetivo deste trabalho foi apresentar uma revisão sobre o impacto da pandemia por COVID-19 no tratamento da dor, além da proposição de uma alternativa frente ao presente contexto, como a telereabilitação. CONTEÚDO: Trata-se de uma revisão integrativa realizada nas bases de dados: LILACS, Scielo, Pubmed, Scopus, Web of Science, PubCovid e bases de dados dedicadas a publicação de Preprints sobre a temática COVID-19, como Psyarxiv e Preprint MedRxiv. Na presente revisão pretendemos evidenciar os prejuízos cognitivos, emocionais e comportamentais relacionadas à dor durante a pandemia causada pela COVID-19. CONCLUSÃO: O contexto pandêmico e isolamento social pode interferir negativamente nas respostas de sensibilidade e no tratamento da dor, seja pelo aumento em eventos de dor na população, impactados pelos prejuízos sociais e psicológicos ou pela interrupção do atendimento presencial durante a pandemia. Neste ponto, recomendamos o avanço gradual na abordagem das limitações atuais do tratamento e propomos um roteiro futuro para enfrentar possíveis desafios que possam se apresentar.

15.
Brain Res Bull ; 165: 118-128, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33038420

RESUMEN

Neuropathic pain (NP) is a challenge due to our limited understanding of the mechanisms that initiate and maintain chronic pain. The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is an important area of the emotional and cognitive components of pain and pharmacological systems can interact into the neocortex to elaborate the chronic pain. This work aimed to investigate the pharmacological cross-talk between synaptic neurotransmission, neuroanatomical approaches and NP conditions. A bidirectional neural tract tracer, the 3000-molecular-weight biodextran (BDA) was microinjected into the PrL cortex. The mechanical withdrawal threshold (MWT) was recorded by a von Frey test, and the effect of prelimbic cortex CB1, NMDA, and TRPV1 receptor modulation was evaluated 21 days after chronic constriction injury (CCI) of the sciatic nerve in male Wistar rats. Microinjection of a bidirectional neurotracer in the PrL cortex showed connections with the lateral division of the mediodorsal thalamic nucleus (MDL), central division of the mediodorsal thalamic nucleus (MDC), centrolateral thalamic nucleus (CL), ventromedial thalamic nucleus (VM), and the paracentral thalamic nucleus (PC). In detail, AM251, a CB1 receptor antagonist (at 50, 100 and 200 pmol) microinjections intra-PrL cortex decreased the MWT. Administrations of 6-iodonordihydrocapsaicin (6-I-CPS), a transient receptor potential vanilloid type 1 (TRPV1) antagonist, at 3 nmol and the endocannabinoid anandamide (AEA) at 50 and 100 pmol increased the MWT. AEA at 200 pmol injected in the PrL cortex decreased the MWT, and this hyperalgesic effect was blocked by 6-I-CPS at 3 nmol. The AEA (at 100 pmol) anti-allodynic effect was attenuated by AM251 (at 5 pmol). The TRPV1 selective agonist N-oleoyldopamine (OLDA) at 10 µM decreased the MWT. The blockade of the NMDA receptor with LY235959 (at 8 nmol) and 6-I-CPS (at 3 nmol) reversed the OLDA (at 10 µM) hyperalgesic effect. These findings showed that the PrL cortex sends pathways to thalamic nuclei that can mediate the nociception. We also suggest that the PrL cortex is involved in the potentiation and maintenance of mechanical allodynia by NMDA and TRPV1 receptor activation and that attenuation of this allodynia depends on CB1 receptor activation during NP.


Asunto(s)
Corteza Cerebral/metabolismo , Neuralgia/metabolismo , Receptor Cannabinoide CB1/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Canales Catiónicos TRPV/metabolismo , Animales , Antagonistas de Receptores de Cannabinoides/farmacología , Capsaicina/análogos & derivados , Capsaicina/farmacología , Corteza Cerebral/efectos de los fármacos , Modelos Animales de Enfermedad , Antagonistas de Aminoácidos Excitadores/farmacología , Masculino , Ratas , Ratas Wistar
16.
SciELO Preprints; jun. 2020.
Preprint en Inglés | SciELO Preprints | ID: pps-710

RESUMEN

In response to the outbreak of the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), pathogen of the new coronavirus disease (COVID-19), several sectors and social activities have been affected, including education. At first, it is explained that educators and students can feel fragile during and after the SARS-CoV-2 outbreak. Subsequently, it is discussed that their relationship ought to be carefully established given the triggering of psychological and neuropsychiatric effects arising from neural coding and plasticity processes, which result in the formation of positive and negative memories in the short to long term. Finally, it is pointed out that the SARS-CoV-2 pandemic generates a need for adequacy and adaptation for the significant attention to students during the re-starting of studies, given that possible disorders of sensory modulation and involvement of limbic brain areas triggered in situations of risk of death, potential or real threat, can happen. It is assumed that at times of the SARS-CoV-2 pandemic, in addition to preserving life, one of the challenges is the behavioural (re)organisation, which includes habits from the educational context that need to contemplate a scientific perspective, seeking to transform the consequences of the pandemic fear on opportunities to reinforcement of familiar links. In the context of modern rationality, the SARS-CoV-2 pandemic is also a period to think about the relationship between scientific knowledge and common sense. With this logic, neurosciences can develop a new format for the teaching-learning process, so that educators and students experiencing the pandemic threatening do not manifest psychological distress and secondary consequences. Therefore, education can be considered a central space in decision-making in the face of SARS-CoV-2 pandemic. In this sense, the urgency of a multidisciplinary strategies development is highlighted, connecting the synergy between neurosciences and education after the COVID-19 pandemic.

17.
J Neurosci Res ; 98(2): 338-352, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31396990

RESUMEN

The chronic constriction injury (CCI) of the sciatic nerve is a nerve injury-based model of neuropathic pain (NP). Comorbidities of NP such as depression, anxiety, and cognitive deficits are associated with a functional reorganization of the medial prefrontal cortex (mPFC). Here, we have employed an adapted model of CCI by placing one single loose ligature around the sciatic nerve in mice for investigating the alterations in sensory, motor, affective, and cognitive behavior and in electrophysiological and biochemical properties in the prelimbic division (PrL) of the mPFC. Our adapted model of CCI induced mechanical allodynia, motor, and cognitive impairments and anxiety- and depression-like behavior. In the PrL division of mPFC was observed an increase in GABA and a decrease in d-aspartate levels. Moreover an increase in the activity of neurons responding to mechanical stimulation with an excitation, mPFC (+), and a decrease in those responding with an inhibition, mPFC (-), was found. Altogether these findings demonstrate that a single ligature around the sciatic nerve was able to induce sensory, affective, cognitive, biochemical, and functional alterations already observed in other neuropathic pain models and it may be an appropriate and easily reproducible model for studying neuropathic pain mechanisms and treatments.


Asunto(s)
Ácido Aspártico/metabolismo , Conducta Animal/fisiología , Neuralgia/fisiopatología , Umbral del Dolor/fisiología , Traumatismos de los Nervios Periféricos/fisiopatología , Nervio Ciático/lesiones , Ácido gamma-Aminobutírico/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/fisiopatología , Cognición/fisiología , Masculino , Ratones , Neuralgia/etiología , Neuralgia/metabolismo , Dimensión del Dolor , Traumatismos de los Nervios Periféricos/complicaciones , Traumatismos de los Nervios Periféricos/metabolismo , Estimulación Física
18.
Psicol. pesq ; 14(spe): 102-119, 2020.
Artículo en Portugués | LILACS-Express | LILACS, Index Psicología - Revistas | ID: biblio-1155175

RESUMEN

A esquizofrenia é um transtorno mental grave e incapacitante que tem como critérios diagnósticos sintomas positivos, negativos, discurso e pensamento desorganizado ou catatônico. Cursa com importantes disfunções cognitivas com impactos na atenção, na função executiva, em memória operacional e de trabalho, entre outras. Tais déficits podem estar presentes antes dos sintomas positivos ou mesmo, de maneira subsindrômica desde a infância desses indivíduos. A hipótese dopaminérgica é a mais aceita na gênese das disfunções neuroquímicas, mas há cada vez mais evidência do envolvimento de outros sistemas como o glutamatérgico e o serotoninérgico. No que se refere especificamente aos déficits cognitivos, destacam-se disfunções em córtex pré-frontal, especialmente sua porção dorsolateral e suas conexões com o hipocampo. Entende-se ainda que é muito importante a avaliação cognitiva das pessoas acometidas por essa patologia e existem baterias de testes neuropsicológicos disponíveis como é o caso do Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) e de testes validados no Brasil como o Brief Assessment of Cognition in Schizophrenia (BACS). Tendo em vista a elevada perda de funcionalidade e qualidade de vida desses pacientes, sobretudo daqueles mais acometidos na capacidade cognitiva, há uma necessidade de maiores esforços para o entendimento desse complexo transtorno com vistas a tratamentos mais eficazes e até mesmo desenvolvimento de estratégias preventivas.


Schizophrenia is a serious and disabling mental disorder whose diagnostic criteria are positive or negative symptoms, disorganized or catatonic speech and thinking. It takes place with important cognitive dysfunctions with impacts on attention, executive function, working memory, among others. Such deficits may be present before positive symptoms or even, in a subsyndromal manner since the childhood of these individuals. The dopaminergic hypothesis is the most accepted in the genesis of neurochemical disorders, but there is increasing evidence of the involvement of other systems such as glutamatergic and serotonergic. With regard specifically to cognitive deficits, dysfunctions in the prefrontal cortex stand out, especially its dorsolateral portion and its connections with the hippocampus. It is also understood that the cognitive test of people affected by this pathology is very important and there are neuropsychological tests batteries available, such as Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and tests validated in Brazil such as the Brief Assessment of Cognition in Schizophrenia (BACS). Considering the high loss of functionality and life quality of these patients, especially those more affected in cognitive ability, there is a need for greater efforts to understand this complex disorder aiming more effective treatments and even the development of preventive strategies.


La esquizofrenia es un trastorno mental grave e incapacitante cuyos criterios de diagnóstico son síntomas positivos, negativos, habla y pensamiento desorganizados o catatónicos. Se lleva a cabo con importantes disfunciones cognitivas con impactos en la atención, la función ejecutiva, el trabajo y la memoria de trabajo, entre otros. Tales déficits pueden estar presentes antes de los síntomas positivos o incluso, de manera subsindrómica desde la infancia de estos individuos. La hipótesis dopaminérgica es la más aceptada en la génesis de los trastornos neuroquímicos, pero cada vez hay más evidencia de la participación de otros sistemas como el glutamatérgico y el serotoninérgico. Con respecto específicamente a los déficits cognitivos, se destacan las disfunciones en la corteza prefrontal, especialmente su porción dorsolateral y sus conexiones con el hipocampo. También se entiende que la evaluación cognitiva de las personas afectadas por esta patología es muy importante y hay baterías de pruebas neuropsicológicas disponibles, como la Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) y pruebas validadas en Brasil como el Brief Assessment of Cognition in Schizophrenia (BACS). En vista de la alta pérdida de funcionalidad y calidad de vida de estos pacientes, especialmente los más afectados por la capacidad cognitiva, existe la necesidad de realizar mayores esfuerzos para comprender este complejo trastorno con miras a tratamientos más efectivos e incluso el desarrollo de estrategias preventivas.

19.
Neurochem Res ; 44(9): 2068-2080, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31317507

RESUMEN

The mechanisms underlying chronic and neuropathic pain pathology involve peripheral and central sensitisation. The medial prefrontal cortex (mPFC) seems to participate in pain chronification, and glutamatergic neurotransmission may be involved in this process. Thus, the aim of the present work was to investigate the participation of the prelimbic (PrL) area of the mPFC in neuropathic pain as well as the role of N-methyl D-aspartate (NMDA) glutamate receptors in neuropathic pain induced by a modified sciatic nerve chronic constriction injury (CCI) protocol in Wistar rats. Neural inputs to the PrL cortex were inactivated by intracortical treatment with the synapse blocker cobalt chloride (CoCl2, 1.0 mM/200 nL) 7, 14, 21, or 28 days after the CCI or sham procedure. The glutamatergic agonist NMDA (0.25, 1 or 4 nmol) or the selective NMDA receptor antagonist LY235959 (2, 4 or 8 nmol) was microinjected into the PrL cortex 21 days after surgery. CoCl2 administration in the PrL cortex decreased allodynia 21 and 28 days after CCI. NMDA at 1 and 4 nmol increased allodynia, whereas LY235959 decreased mechanical allodynia at the highest dose (8 nmol) microinjected into the PrL cortex. These findings suggest that NMDA receptors in the PrL cortex participate in enhancing the late phase of mechanical allodynia after NMDA-induced increases and LY235959-induced decreases in allodynia 21 days after CCI. The glutamatergic system potentiates chronic neuropathic pain by NMDA receptor activation in the PrL cortex. Mechanism of neuropathic pain. The infusion of CoCl2, a synapse activity blocker, into the prelimbic (PrL) division of the medial prefrontal cortex (mPFC) decreased the severity of mechanical allodynia, showing the late participation of the limbic cortex. The glutamatergic system potentiates chronic neuropathic pain via NMDA receptor activation in the PrL cortex.


Asunto(s)
Neuralgia/metabolismo , Nervios Periféricos/metabolismo , Corteza Prefrontal/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animales , Cobalto/farmacología , Hiperalgesia/tratamiento farmacológico , Isoquinolinas/farmacología , Masculino , N-Metilaspartato/farmacología , Neuralgia/tratamiento farmacológico , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Corteza Prefrontal/efectos de los fármacos , Ratas Wistar , Transmisión Sináptica/efectos de los fármacos
20.
J Psychopharmacol ; 33(1): 51-61, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30407114

RESUMEN

BACKGROUND: There is a controversy regarding the key role played by opioid peptide neurotransmission in the modulation of panic-attack-related responses. AIMS: Using a prey versus rattlesnakes paradigm, the present work investigated the involvement of the endogenous opioid peptide-mediated system of the inferior colliculus in the modulation of panic attack-related responses. METHODS: Wistar rats were pretreated with intracollicular administration of either physiological saline or naloxone at different concentrations and confronted with rattlesnakes ( Crotalus durissus terrificus). The prey versus rattlesnake confrontations were performed in a polygonal arena for snakes. The defensive behaviors displayed by prey (defensive attention, defensive immobility, escape response, flat back approach and startle) were recorded twice: firstly, over a period of 15 min the presence of the predator and a re-exposure was performed 24 h after the confrontation, when animals were exposed to the experimental enclosure without the rattlesnake. RESULTS: The intramesencephalic non-specific blockade of opioid receptors with microinjections of naloxone at higher doses decreased both anxiety- (defensive attention and flat back approach) and panic attack-like (defensive immobility and escape) behaviors, evoked in the presence of rattlesnakes and increased non-defensive responses. During the exposure to the experimental context, there was a decrease in duration of defensive attention. CONCLUSIONS: These findings suggest a panicolytic-like effect of endogenous opioid receptors antagonism in the inferior colliculus on innate (panic attack) and conditioned (anticipatory anxiety) fear in rats threatened by rattlesnakes.


Asunto(s)
Miedo/efectos de los fármacos , Colículos Inferiores/efectos de los fármacos , Naloxona/farmacología , Péptidos Opioides/fisiología , Trastorno de Pánico/tratamiento farmacológico , Animales , Reacción de Prevención/efectos de los fármacos , Crotalus , Mecanismos de Defensa , Reacción de Fuga/efectos de los fármacos , Miedo/psicología , Colículos Inferiores/fisiología , Masculino , Péptidos Opioides/antagonistas & inhibidores , Ratas , Ratas Wistar
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