Enriched environment prevents hypernociception and depression-like behavior in a psychiatric disorder and neuropathic pain comorbidity experimental condition.

Pain is a multifactorial debilitating condition associated with some psychiatric comorbidities such as generalized anxiety and depression. Concerning pharmacological treatment, which is often inefficient or associated with intense side effects, the physical and social context may be fundamental for patient's health improvement. In this sense, we sought to assess the impact of an enriched environment (EE) on neuropathic pain (NP) and depression comorbid.

In Vivo Neural Tract Tracing Procedures: Unravelling Neural Hodology Using Fluorescent and Non-fluorescent Neural Tract Tracers, Optogenetic Approach, and Diffusion Tensor Neurotractography Protocols.

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.

Nitric oxide-signalling affects panic-like defensive behaviour and defensive antinociception neuromodulation in the prelimbic cerebral cortex.

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.

Cannabidiol in the dorsal hippocampus attenuates emotional and cognitive impairments related to neuropathic pain: The role of prelimbic neocortex-hippocampal connections.

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.

Mygalin, an Acanthoscurria gomesiana spider-derived synthetic, modulates haloperidol-induced cataleptic state in mice.

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.

Effect of electrical and chemical (activation versus inactivation) stimulation of the infralimbic division of the medial prefrontal cortex in rats with chronic neuropathic pain.

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.

Acanthoscurria gomesiana spider-derived Mygalin in the prelimbic prefrontal cortex modulates neuropathic pain and depression comorbid.

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.

Cortical Neurostimulation and N-Methyl-D-Aspartate Glutamatergic Receptor Activation in the Dysgranular Layer of the Posterior Insular Cortex Modulate Chronic Neuropathic Pain.

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").

Infralimbic medial prefrontal cortex alters electroacupuncture effect in animals with neuropathic chronic pain.

Introduction: Morphological reorganization in the neural networks of the medial prefrontal cortex (mPFC) may be involved in the development of chronic neuropathic pain (NP).

Objectives: We investigated whether inactivation and neurostimulation of the infralimbic division (IFL) of the mPFC alter electroacupuncture-induced analgesia (EIA) at 2 Hz and 2/100 Hz in animals with chronic NP.

Methods: Wistar rats were submitted to chronic constrictor injury of the ischiadicus nerve (CCI).

The primary motor cortex electrical and chemical stimulation attenuates the chronic neuropathic pain by activation of the periaqueductal grey matter: The role of NMDA receptors.

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 (M) 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.

CB-cannabinoid-, TRPV-vanilloid- and NMDA-glutamatergic-receptor-signalling systems interact in the prelimbic cerebral cortex to control neuropathic pain symptoms.

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.

An Adapted Chronic Constriction Injury of the Sciatic Nerve Produces Sensory, Affective, and Cognitive Impairments: A Peripheral Mononeuropathy Model for the Study of Comorbid Neuropsychiatric Disorders Associated with Neuropathic Pain in Rats.

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.

Characterization of the sensory, affective, cognitive, biochemical, and neuronal alterations in a modified chronic constriction injury model of neuropathic pain in mice.

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.

Intraperitoneal cannabidiol attenuates neonatal germinal matrix hemorrhage-induced neuroinflamation and perilesional apoptosis.

. As the survival of preterm infants has increased significantly, germinal matrix hemorrhage (GMH) has become an important public health issue. Nevertheless, treatment strategies for the direct neuronal injury are still scarce.

N-methyl-D-aspartate Receptors in the Prelimbic Cortex are Critical for the Maintenance of Neuropathic Pain.

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.

The endogenous opioid system modulates defensive behavior evoked by Crotalus durissus terrificus: Panicolytic-like effect of intracollicular non-selective opioid receptors blockade.

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 Rodent-versus-wild Snake Paradigm as a Model for Studying Anxiety- and Panic-like Behaviors: Face, Construct and Predictive Validities.

Using an innovative approach to study the neural bases of psychiatric disorders, this study investigated the behavioral, morphological and pharmacological bases of panic attack-induced responses in a prey-versus-coral snake paradigm. Mesocricetus auratus was chronically treated with intraperitoneal administration of the selective serotonin uptake inhibitor paroxetine or the gamma aminobutyric acid (GABA)/benzodiazepine receptor agonist alprazolam at three different doses and were then confronted with a venomous coral snake (Micrurus frontalis, Reptilia, Elapidae). The threatened rodents exhibited defensive attention, flat back approaches, defensive immobility, and escape defensive responses in the presence of the venomous snake, followed by increases in Fos protein in limbic structure neurons.

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.

Rationale: Gamma-aminobutyric acid (GABA)ergic neurons of the substantia nigra pars reticulata (SNpr) are connected to the deep layers of the superior colliculus (dlSC). The dlSC, in turn, connect with the SNpr through opioid projections. Nociceptin/orphanin FQ peptide (N/OFQ) is a natural ligand of a Gi protein-coupled nociceptin receptor (ORL1; NOP) that is also found in the SNpr.

Connexions between the dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal grey matter are critical in the elaboration of hypothalamically mediated panic-like behaviour.

The electrical and chemical stimulation of the dorsal periaqueductal grey matter (dPAG) elicits panic-like explosive escape behaviour. Although neurons of the ventromedial hypothalamus (VMH) seem to organise oriented escape behaviour, when stimulated with excitatory amino acids at higher doses, non-oriented/explosive escape reactions can also be displayed. The aim of this work was to examine the importance of reciprocal projections between the VMH and the dPAG for the organisation of this panic-like behaviour.

µ -Opioid receptors in the dorsomedial and ventrolateral columns of the periaqueductal grey matter are critical for the enhancement of post-ictal antinociception.

Generalised tonic and tonic-clonic seizures are followed by significant increase in nociceptive thresholds in both laboratory animals and humans. The endogenous opioid peptides play a role in antinociceptive signalling, and the periaqueductal grey matter (PAG) is recruited to induce analgesia. Thus, the aim of this investigation was to evaluate the role of µ -opioid receptors in the dorsomedial (dm) and ventrolateral (vl) columns of PAG in post-ictal antinociception.

The μ-opioid receptor and 5-HT- and 5HT-serotonergic receptors of the locus coeruleus are critical in elaborating hypoalgesia induced by tonic and tonic-clonic seizures.

It has been proposed that the post-ictal state is associated with the expression of hypoalgesia. It is clear that the projections among the periaqueductal gray matter (PAG), dorsal raphe nucleus (DRN) and locus coeruleus (LC) play a role in pain management. These mesencephalic structures have direct reciprocal opioid and monoaminergic projections to the LC that can possibly modulate post-ictal hypoalgesia.

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.

Inhibition of GABAergic neural inputs to dorsal columns of the periaqueductal grey matter (dPAG), posterior (PH) and dorsomedial (DMH) hypothalamic nuclei elicits distinct types of escape behavioural reactions. To differentiate between the variety and intensity of panic-related behaviours, the pattern of defensive behaviours evoked by blockade of GABAA receptors in the DMH, PH and dPAG were compared in a circular open-field test and in a recently designed polygonal arena. In the circular open-field, the defensive behaviours induced by microinjection of bicuculline into DMH and PH were characterised by defensive alertness behaviour and vertical jumps preceded by rearing exploratory behaviour.

The role of dorsomedial and ventrolateral columns of the periaqueductal gray matter and in situ 5-HT₂A and 5-HT₂C serotonergic receptors in post-ictal antinociception.

The periaqueductal gray matter (PAG) consists in a brainstem structure rich in 5-hydroxytryptamine (5-HT) inputs related to the modulation of pain. The involvement of each of the serotonergic receptor subtypes found in PAG columns, such as the dorsomedial (dmPAG) and the ventrolateral (vlPAG) columns, regarding post-ictal antinociception have not been elucidated. The present work investigated the participation of the dmPAG and vlPAG columns in seizure-induced antinociception.

Neuroanatomical and neuropharmacological approaches to postictal antinociception-related prosencephalic neurons: the role of muscarinic and nicotinic cholinergic receptors.

Several studies have suggested the involvement of the hippocampus in the elaboration of epilepsy. There is evidence that suggests the hippocampus plays an important role in the affective and motivational components of nociceptive perception. However, the exact nature of this involvement remains unclear.

Involvement of prelimbic medial prefrontal cortex in panic-like elaborated defensive behaviour and innate fear-induced antinociception elicited by GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei: role of the endocannabinoid CB1 receptor.

It has been shown that GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei (DMH and VMH, respectively) induces elaborated defensive behavioural responses accompanied by antinociception, which has been utilized as an experimental model of panic attack. Furthermore, the prelimbic (PL) division of the medial prefrontal cortex (MPFC) has been related to emotional reactions and the processing of nociceptive information. The aim of the present study was to investigate the possible involvement of the PL cortex and the participation of local cannabinoid CB1 receptors in the elaboration of panic-like reactions and in innate fear-induced antinociception.