Acetylcholine-mediated neurotransmission within the nucleus raphe magnus exerts a key role in the organization of both interictal and postictal antinociception

AbstractThe role of the acetylcholine-mediated system in the organization of postictal antinociception was investigated. For this purpose, nicotinic and muscarinic cholinergic receptor antagonists were microinjected into the nucleus raphe magnus (NRM), a key structure of the endogenous pain inhibitory system. After the tail-flick test baseline recording, male Wistar rats (N=8 per group) were submitted to stereotaxic surgery for the introduction of a guide cannula aiming at the NRM. Five days after surgery, atropine or mecamylamine (1µg/0.2µL, 3µg/0.2µL, or 5µg/0.2µL) was microinjected into the NRM. The tail-flick withdrawal latency was recorded immediately after peripheral treatment with pentylenetetrazole (PTZ) (64mg/kg), in two different interictal time windows, and for 130minutes after the last seizure evoked by intraperitoneal injection of PTZ. The blockade of GABA-mediated Cl– influx caused tonic–clonic convulsions in all animals followed by sustained postictal antinociception lasting 110minutes after seizures; the nociceptive threshold was also found to be high in interictal periods. Pretreatment of the NRM with either atropine or mecamylamine antagonized both interictal and postictal antinociception, suggesting the involvement of cholinergic mechanisms recruiting muscarinic and nicotinic cholinergic receptors of the NRM in the organization of tonic–clonic seizure-induced antinociception

Repeated exposure of naïve and peripheral nerve-injured mice to a snake as an experimental model of post-traumatic stress disorder and its co-morbidity with neuropathic pain

© 2020 Elsevier B.V. Confrontation of rodents by natural predators provides a number of advantages as a model for traumatic or stressful experience. Using this approach, one of the aims of this study was to investigate a model for the study of post-traumatic stress disorder (PTSD)-related behaviour in mice. Moreover, because PTSD can facilitate the establishment of chronic pain (CP), and in the same way, patients with CP have an increased tendency to develop PTSD when exposed to a traumatic event, our second aim was to analyse whether this comorbidity can be verified in the new paradigm. C57BL/6 male mice underwent chronic constriction injury of the sciatic nerve (CCI), a model of neuropathic CP, or not (sham groups) and were submitted to different threatening situations. Threatened mice exhibited enhanced defensive behaviours, as well as significantly enhanced risk assessment and escape behaviours during context reexposure. Previous snake exposure reduced open-arm time in the elevated plus-maze test, suggesting an increase in anxiety levels. Sham mice showed fear-induced antinociception immediately after a second exposure to the snake, but 1 week later, they exhibited allodynia, suggesting that multiple exposures to the snake led to increased nociceptive responses. Moreover, after reexposure to the aversive environment, allodynia was maintained. CCI alone produced intense allodynia, which was unaltered by exposure to either the snake stimuli or reexposure to the experimental context. Together, these results specifically parallel the behavioural symptoms of PTSD, suggesting that the snake/exuvia/reexposure procedure may constitute a useful animal model to study PTSD

PHYSICAL, EMOTIONAL, AND SOCIAL PAIN DURING COVID-19 PANDEMIC-RELATED SOCIAL ISOLATION

The recognition and management of the socio-emotional pain facing the COVID-19 pandemic refer to different, but interdependent, clues regarding cognitive and emotional aspects of the pandemic threat, considering the need of social distancing as a prophylactic procedure to avoid spreading the pathogen. The socio-emotional condition at the time of outbreak subsidizes the (re)modulation of interactive neural circuits underlying the risk assessment behaviour at physical, emotional, and social levels. Experiences of social isolation, exclusion or affective loss are generally considered to be some of the most “painful” things that people face. The threats of social disconnection are processed by some of the same neural structures that process basic threats to survival. The lack of social connection can be "painful" due to an overlap in the neural circuitry responsible for both physical and emotional pain related to feelings of social rejection. Indeed, many of us go to great lengths to avoid situations that may engender these experiences. Because of this, this work focusses on times of pandemic, the somatization mentioned above seeks the interconnection and/or interdependence between neural systems related to emotional and cognitive processes, so that the person involved in that aversive social environment becomes aware of himself, the others, and the threatening situation experienced to avoid daily psychological and neuropsychiatric effects. Social distancing during the isolation evokes the formation of social distress, raising the intensity of learned fear that people acquire, consequently enhancing the emotional and social pain

Antinociception induced by acute oral administration of sweet substance in young and adult rodents: The role of endogenous opioid peptides chemical mediators and mu(1)-opioid receptors

The present work aimed to investigate the effects of acute sucrose treatment on the perception of painful stimuli. Specifically, we sought to determine the involvement of the endogenous opioid peptide-mediated system as well as the role of the mu(1)-opioid receptor in antinociception organisation induced by acute sucrose intake. Nociception was assessed with the tail-flick test in rats (75, 150 and 250 g) of different ages acutely pre-treated with 500 mu L. of a sucrose solution (25, 50, 150 and 250 g/L) or tap water. Young and Adult rats (250 g) showed antinociception after treatment with 50 g/L (during 5 min) and 150 g/L and 250 g/L (during 20 min) sucrose solutions. Surprisingly, this antinociception was more consistent in mature adult rodents than in pups. To evaluate the role of opioid systems, mature adult rodents were pre-treated with different doses (0.25, 1 or 4mg/kg) of the non-selective opioid receptor antagonist naloxone, the selective pi-opioid receptor antagonist naloxonazine or vehicle followed by 250 g/L sucrose solution treatment. Sucrose-induced antinociception was reduced by pre-treatment with both naloxone and naloxonazine. The present findings suggest that sweet substance-induced hypo-analgesia is augmented by increasing sucrose concentrations in young and adult rodents. Acute oral sucrose treatment inhibits pain in laboratory animal by mediating endogenous opioid peptide and mu(1)-opioid receptor actions. (C) 2011 Elsevier Inc. All rights reserved.FAPESPFAPESP [proc. 03/03118-0, proc. 01/03752-6, proc. 03/05256-1, proc. 2009/17258-5, TT-2, proc. 02/01497-1]FAEPAFAEPA [proc. 1291/97, 355/2000, 68/2001, 15/2003, 6/2004]CNPq [proc. 301905/2010-0, proc. 501858/2005-9, proc. 372654/2006-1, proc. 372810/2008-0, proc. 372877/2010-9]CNPqCAPESCAPE

Paradoxical Kinesia Induced by Nightmare: Unique Case Report and Insights regarding the Neural Mechanism Based on Human and Rat Studies

Introduction: Bradykinesia, characterized by slowed movement, stands out as a primary symptom observed in individuals with Parkinson’s disease (PD). Nonetheless, there are instances where PD patients exhibit sudden and effective movements despite the presence of bradykinesia. This phenomenon, referred to as paradoxical kinesia, has remained a subject of interest for neuroscientists, who have struggled to unravel its underlying neural mechanisms for decades. Case Presentation: We describe a patient who is suffering from advanced PD. The patient has severe motor limitations, including difficulty rising from bed and walking, as well as cognitive decline and visual impairment. However, an interesting occurrence took place during a nightmare episode. Surprisingly, the patient was able to get out of bed and quickly run away from the perceived threat within the nightmare, without any assistance. Conclusion: This report presents the first documented case of paradoxical kinesia induced by nightmares in a patient with PD. This phenomenon raises questions about the neurological mechanisms involved, which are still not fully understood. Based on existing research conducted on both animal and human subjects, we propose that after processing the emotion of fear, the brain aversive system activates motor outputs to generate appropriate behavior. Thus, the brain aversive system converts the emotion of fear into action through projections from the inferior colliculus to motor-related areas such as the mesencephalic locomotor region, pontine nuclei, and substantia nigra

Physical, emotional, and social pain during COVID-19 pandemic-related social isolation

29 páginasThe socio-emotional condition during the COVID-19 pandemic subsidises the (re)modulation of interactive neural circuits underlying risk assessment behaviour at the physical, emotional, and social levels. Experiences of social isolation, exclusion, or affective loss are generally considered some of the most “painful” things that people endure. The threats of social disconnection are processed by some of the same neural structures that process basic threats to survival. The lack of social connection can be “painful” due to an overlap in the neural circuitry responsible for both physical and emotional pain related to feelings of social rejection. Indeed, many of us go to great lengths to avoid situations that may engender these experiences. Accordingly, this work focuses on pandemic times; the somatisation mentioned above seeks the interconnection and/or interdependence between neural systems related to emotional and cognitive processes such that a person involved in an aversive social environment becomes aware of himself, others, and the threatening situation experienced and takes steps to avoid daily psychological and neuropsychiatric effects. Social distancing during isolation evokes the formation of social distress, increasing the intensity of learned fear that people acquire, consequently enhancing emotional and social pain

Influence of treadmill training on motor performance and organization of exploratory behavior in Meriones unguiculatus with unilateral ischemic stroke: Histological correlates in hippocampal CA1 region and the neostriatum

This study examined the effects of motor stimulation via treadmill on the behavior of male gerbils after external carotid ischemic brain lesion. The animals were assigned to five groups; ischemic with no stimulation (SIG), ischemic with stimulation (SIG 12/24/48/72 It after surgery), non-ischemic with no stimulation (CC), non-ischemic with stimulation (CE) and sham, surgery without occlusion with no stimulation (SH). All the animals were tested in the open-field (OF) and rotarod (RR), 4 days after surgery in order to evaluate exploratory behaviors and motor performance. Data were submitted to one-way variance (ANOVA) and Dunnett`s post hoc comparisons. SIG and SIG 12 groups showed a significant decrease in motor response (crossing) when compared to the control group (CC) (F = 20.65, P < 0.05) in the OF. SIG 12 group showed an increase in grooming behavior (F = 23.136, P < 0.05) and all ischemia groups (SIG, SIG 12/24/48/72) spent less time on the RR (F = 10.40, P < 0.05), when compared to the control group (CC). Histological analyses show extensive lesions in the hippocampus and neostriatum for all groups with ischemia (SIG, SIG 12/24/48/72), which are structures involved in the organization of motor behavior. Interestingly, the most pronounced damage was found in animals submitted to motor stimulation 12 h after ischemia which can be correlated to the increased number of grooming behavior showed by them in the OF. These findings suggest that motor stimulation through treadmill training improve motor behavior after ischemia, except when it starts 12h after surgery. (c) 2007 Elsevier Ireland Ltd. All rights reserved

GABA(A) receptor blockade in dorsomedial and ventromedial nuclei of the hypothalamus evokes panic-like elaborated defensive behaviour followed by innate fear-induced antinociception

Dysfunction in the hypothalamic GABAergic system has been implicated in panic syndrome in humans. Furthermore, several studies have implicated the hypothalamus in the elaboration of pain modulation. Panic-prone states are able to be experimentally induced in laboratory animals to study this phenomenon. The aim of the present work was to investigate the involvement of medial hypothalamic nuclei in the organization of panic-like behaviour and the innate fear-induced oscillations of nociceptive thresholds. The blockade of GABA(A) receptors in the neuronal substrates of the ventromedial. or dorsomedial hypothalamus was followed by elaborated defensive panic-like reactions. Moreover, innate fear-induced antinociception was consistently elicited after the escape behaviour. The escape responses organized by the dorsomedial and ventromedial hypothalamic nuclei were characteristically more elaborated, and a remarkable exploratory behaviour was recorded during GABA(A) receptor blockade in the medial hypothalamus. The motor characteristic of the elaborated defensive escape behaviour and the patterns of defensive alertness and defensive immobility induced by microinjection of the bicuculline either into the dorsomedial. or into the ventromedial hypothalamus were very similar. This was followed by the same pattern of innate fear-induced antinociceptive response that lasted approximately 40 min after the elaborated defensive escape reaction in both cases. These findings suggest that dysfunction of the GABA-mediated neuronal system in the medial hypothalamus causes panic-like responses in laboratory animals, and that the elaborated escape behaviour organized in both dorsomedial and ventromedial hypothalamic nuclei are followed by significant innate-fear-induced antinociception. Our findings indicate that the GABA(A) receptor of dorsomedial and ventromedial hypothalamic nuclei are critically involved in the modulation of panic-like behaviour. (C) 2009 Elsevier B.V. All rights reserved.FAPESP[2007/01174-1]FAPESP[2009/01153-0]FAPESP[03/05256-1]FAPESP[TT-2]FAPESP[02/01497-1]CAPES-PROEXCNPq[304421/2007-3]CNPq[057/2005]CNPq[04/2008-AT]CNPq[501858/2005-9]CNPq[500896/2008-9]Pain Imaging Neuroscience (PaIN) Group, at the Physiology, Anatomy and Genetics Department[200629/2005-0]Clinical Neurology (FMRIB Centre) Department at the University of Oxford, United Kingdo