Cristofer André Caous

Neuronal connections of the paratrigeminal nucleus: a topographic analysis of neurons projecting to bulbar, pontine and thalamic nuclei related to cardiovascular, respiratory and sensory functions

The paratrigeminal nucleus, which receives sensory input from trigeminal, glossopharyngeal and vagus nerves, has efferent projections to bulbar, pontine and possibly to thalamic structures associated with nociception, thermoregulation and cardiovascular control. Anterograde neuronal tracers were used to study paratrigeminal efferent connections. Labeled terminal fibers, evidencing bilateral efferent paratrigeminal projections were observed in the medial and caudal solitary tract (sol), lateral reticular nucleus (LRt), ambiguus nucleus (Amb), rostroventrolateral reticular nucleus (RVL), while ipsilateral projections were found in the parabrachial (PB) nuclei and ventral portion of the ventral posteromedial thalamic nucleus (VPM). This extends other findings that describe paratrigeminal projections. Retrograde neuronal transport tracers, microinjected in the defined projection areas were used to map distribution of the paratrigeminal neurons originating different efferent connections. Microinjection of latex microspheres containing fluorescein or rhodamine and Fluoro-gold in the ventral VPM, PB, RVL, Amb, LRt and NTS revealed sets of labeled paratrigeminal nucleus neurons respectively organised in a rostral-caudal sequence. The largest extent of the paratrigeminal nucleus (medial portion) contained neurons projecting to the RVL/Amb, structures associated with cardiovascular regulation. The data show a segmented topographical organization of the nucleus, with different sets of neurons within delimited segments, projecting to neuronal structures associated with different functions. This points to a complex and extensive role for the paratrigeminal nucleus in the integration of somatosensory reflexes related to cardiovascular, respiratory and pain mechanisms. The nucleus may act as a medullary relay interposed between sensory afferents and different structures related to homoeostatic functions.

Projections of the paratrigeminal nucleus to the ambiguus, rostroventrolateral and lateral reticular nuclei, and the solitary tract

The paratrigerminal nucleus (Pa5), a constituent of the spinal interstitial system, was linked to the pressor effect caused by bradykinin injected in the dorsal lateral medulla of the rat. The nucleus receives primary afferent sensory fibers contained in branches of the trigeminal, glossopharyngeal and vagus nerves. In this investigation connections of the paratrigeminal nucleus to other medullary structures were studied with the use of retrograde and anterograde neuronal tracers. Fluorescent light microscopy analyses of medullary sections of rats injected with the retrograde transport tracer Fluoro-gold in the nucleus of the solitary tract (NTS) or in the pressor area of the rostral ventrolateral medulla (RVLM) revealed labeled neuronal cell bodies in the ipsi- and contralateral Pa5. FluoroGold microinjections in the caudal ventrolateral medulla (CVLM) did not produce fluorescent labeling of Pa5 neurons. Microinjection of the anterograde transport neuronal tracer biocytin in the Pa5 produced bilateral labeling of the solitary tract (sol). rostroventrolateral reticular nucleus (RVL), ambiguus nucleus (Amb), lateral reticular nucleus (LRt) and ipsilateral parabrachial nuclei, but not the contralateral Pa5. Confocal laser microscopy showed fluorescence labeling of fibers and presumptive terminal varicosities in the NTS, RVL, Amb and LRt. The present findings showing the paratrigeminal nucleus interposed between sensory afferent and stuctures associated to cardiovascular and respiratory functions, suggest that the structure may act as a medullary relay nucleus for sensory stimuli directly connecting primary afferents to structures mediating cardiovascular and respiratory reflexes.

A importância da integração da espiritualidade e da religiosidade no manejo da dor e dos cuidados paliativos

Background: Pain is one of the most common physical complaints which negatively affects the patient’s quality of life. Patients with chronic pain are difficult and often frustrating to treat. Objective: To describe the current strategies for approaching patients with chronic pain based on scientific literature, emphasizing measures related to spirituality and religiosity. Method: For the present work, authors reviewed data supporting the application of clinical procedures regarding to chronic pain and palliative care with the importance of spirituality background incorporation based on indexed Medline data. Results: Many studies have demonstrated a positive association between spirituality and religiosity and improvement of chronic diseases’ variables and markers. Conclusion: As religiosity and spirituality are notoriously related to the patient’s clinical improvement, it is highly important that the recognition of these aspects and their incorporation in the management of patients with chronic pain be conducted by health professionals.

Cardiovascular responses to sciatic nerve stimulation are blocked by paratrigeminal nucleus lesion

The paratrigeminal nucleus (Pa5) receives primary sensory inputs from the vagus, glossopharyngeal, and trigeminal nerves and has efferent projections to the nucleus of the solitary tract (NTS), rostroventrolateral reticular nucleus (RVL), as well as to the nucleus ambiguus (Amb), lateral reticular (LRt), parabrachial (PB) and ventral posteromedial thalamic (VPM) nuclei, suggesting that it may play a significant role in cardiovascular responses to nociceptive stimuli. The aim of the present study was to evaluate the effects of unilateral lesions of the Pa5 on cardiovascular alterations induced by afferent somatic sensory nerve stimulation (SNS), also known as the somatosympathetic reflex (SSR). Cardiovascular responses were recorded in rats following either sham operation or unilateral lesions of the Pa5 with ibotenic acid. Mean arterial blood pressure (MAP) increased after SNS, which in sham-lesioned animals raised from 95 +/- 4 to 115 +/- 2 mmHg. Ipsilateral Pa5 lesion did not significantly reduce the pressor response to SNS (from 91 +/- 7 to 107 +/- 4 mmHg increase of baseline MAP). On the other hand, contralateral Pa5 lesion significantly reduced the response to SNS (from 99 +/- 5, to 104 +/- 2 mmHg). Sciatic nerve stimulation did not alter heart rate (HR) neither did ipsi- or contralateral Pa5 lesion HR baseline response level. These findings support a crucial role for the Pa5 in cardiovascular regulation, by relaying SSR input evoked by peripheral nerve stimulation.

Sensory sciatic nerve afferent inputs to the dorsal lateral medulla in the rat

Investigations show the paratrigeminal nucleus (Pa5) as an input site for sensory information from the sciatic nerve field. Functional or physical disruption of the Pa5 alters behavioral and somatosensory responses to nociceptive hindpaw stimulation or sciatic nerve electrostimulation (SNS), both contralateral to the affected structure. The nucleus, an input site for cranial and spinal nerves, known for orofacial nociceptive sensory processing, has efferent connections to structures associated with nociception and cardiorespiratory functions. This study aimed at determining the afferent sciatic pathway to dorsal lateral medulla by means of a neuronal tract-tracer (biocytin) injected in the iliac segment of the sciatic nerve. Spinal cord samples revealed bilateral labeling in the gracile and pyramidal or cuneate tracts from survival day 2 (lumbar L1/L2) to day 8 (cervical C2/C3 segments) following biocytin application. From day 10 to day 20 medulla samples showed labeling of the contralateral Pa5 to the injection site. The ipsilateral paratrigeminal nucleus showed labeling on day 10 only. The lateral reticular nucleus (LRt) showed fluorescent labeled terminal fibers on day 12 and 14, after tracer injection to contralateral sciatic nerve. Neurotracer injection into the LRt of sciatic nerve-biocytin-treated rats produced retrograde labeled neurons soma in the Pa5 in the vicinity of biocytin labeled nerve terminals. Therefore, Pa5 may be considered one of the first sites in the brain for sensory/nociceptive inputs from the sciatic nerve. Also, the findings include Pa5 and LRt in the neural pathway of the somatosympathetic pressor response to SNS and nocifensive responses to hindpaw stimulation.

Kinin and opioid receptors in the paratrigeminal nucleus modulate the somatosensory reflex to rat sciatic nerve stimulation

The influence of kinin and opioid receptor blockade in the paratrigeminal nucleus (Pa5) on the somatosensory reflex (SSR) to sciatic nerve stimulation (SNS) was assessed in anaesthetized-paralyzed rats. SNS (square 1 ms pulses at 0.6 mA and 20 Hz for 10s) increased mean arterial pressure from 87+/-3 to 106+/-3 mmHg. Pressor responses to SNS were reduced 40-60% by HOE-140 and LF 16-0687 (B2 receptor antagonists; 20 and 100 pmol respectively), CTOP or nor-binaltorphimine (mu and kappa opioid receptor antagonists, respectively; 1 microg) but potentiated by naltrindole (delta opioid receptor antagonist) receptor antagonist microinjections into the contralateral (but not ipsilateral) Pa5. The SSR to sciatic nerve stimulation was not changed by B1 kinin receptor or NK1, NK2 and NK3 tachykinin receptor antagonists administered to the Pa5. Capsaicin pretreatment (40 mg/kg/day, 3 days) abolished the effects of the opioid receptor antagonists, but did not change the effect of kinin B2 receptor blockade on the SSR. Thus, the activity of B2 and opioid receptor-operated mechanisms in the Pa5 contribute to the SSR in the rat, suggesting a role for these endogenous peptides in the cardiovascular responses to SNS.

The role of the paratrigeminal nucleus in the pressor response to sciatic nerve stimulation in the rat

The paratrigeminal nucleus (Pa5), an input site for spinal, trigeminal, vagus and glossopharyngeal afferents, is a recognized site for orofacial nociceptive sensory processing. It has efferent connections to brain structures associated with nociception and cardiorespiratory functions. This study aimed at determining the function of the Pa5 on the cardiovascular component of the somatosensory reflex (SSR) to sciatic nerve stimulation (SNS) in paralyzed and artificially-ventilated rats following Pa5 chemical lesions (ibotenic acid), synaptic transmission blockade (CoCl(2)), local anaesthetics (lidocaine) or desensitization of primary afferent fibers (capsaicin). The pressor response to sciatic nerve stimulation at 0.6 mA and 20 Hz (14+/-1 mm Hg) was strongly attenuated by contra- (-80%) or bilateral (-50%) paratrigeminal nucleus lesions. Ipsilateral Pa5 lesions only attenuated the response to 0.1 mA, 20 Hz SNS (-55%). Cobalt chloride or lidocaine injected in the contralateral paratrigeminal nucleus also attenuated the SSR. In capsaicin-treated animals, the pressor responses to 0.1 mA were abolished, whereas the responses to SNS at 0.6 mA were increased from 65 to 100% depending on the stimulus frequency. The paratrigeminal nucleus receives both, excitatory and inhibitory components; the later apparently involving capsaicin-sensitive fiber inputs mostly to the ipsilateral site whereas the capsaicin insensitive excitatory components that respond to high or low frequency stimulation, respectively, target the contralateral and ipsilateral sites. Thus, the paratrigeminal nucleus mediates excitatory and inhibitory components of the somatosensory reflex, representing a primary synapse site in the brain for nociceptive inputs from the sciatic innervation field.

Ultrastructural transneuronal degeneration study of axonal elements within the paratrigeminal nucleus in sinoaortic deafferented rats

OBJECTIVE Morphological study that searched to authenticate the presence of sinoaortic baroreceptor inputs within the dorsolateral medullary nucleus under electron microscopy analysis. METHODS After a 5-day survival period, 9 baroreceptor-denervated rats deeply anaesthetized with equithesin were transcardially perfused and their brains were histologically processed. RESULTS The neuronal cytoarchitecture of the paratrigeminal nucleus comprehends afferent projections from other nuclei that have a distributive character regarding visceral and nociceptive functions in the cardiovascular reflex integration response. CONCLUSION The medial portion of the nucleus receives afferent projections of the rostral ventrolateral medulla, as shown by retrograde neurotracing studies. The present results show that the medial extent of the paratrigeminal nucleus contains degenerated axoplasmic cellular components in sinoaortic deafferented rats. The number of degenerated axonal fibers was also larger in this area of the nucleus.

Return on Scientific Investment RoSI: a PMO dynamical index proposal for scientific projects performance evaluation and management

OBJECTIVE To propose a measure (index) of expected risks to evaluate and follow up the performance analysis of research projects involving financial and adequate structure parameters for its development. METHODS A ranking of acceptable results regarding research projects with complex variables was used as an index to gauge a project performance. In order to implement this method the ulcer index as the basic model to accommodate the following variables was applied: costs, high impact publication, fund raising, and patent registry. The proposed structured analysis, named here as RoSI (Return on Scientific Investment) comprises a pipeline of analysis to characterize the risk based on a modeling tool that comprises multiple variables interacting in semi-quantitatively environments. RESULTS This method was tested with data from three different projects in our Institution (projects A, B and C). Different curves reflected the ulcer indexes identifying the project that may have a minor risk (project C) related to development and expected results according to initial or full investment. CONCLUSION The results showed that this model contributes significantly to the analysis of risk and planning as well as to the definition of necessary investments that consider contingency actions with benefits to the different stakeholders: the investor or donor, the project manager and the researchers.