Mecanismos de modulación central del dolor: revisión de la literatura / Mechanisms of central pain modulation: literature review

RESUMEN: La percepción del dolor resulta de múltiples y dinámicos mecanismos en el sistema nervioso central (SNC) y periférico que inhiben o facilitan el estímulo y respuesta nociceptiva. Sin embargo, la principal capacidad de modulación esta a cargo del SNC. Los estímulos nociceptivos son detectados por terminaciones nerviosas libres de neuronas periféricas que sinaptan con neuronas aferentes secundarias de la médula espinal. Luego estas fibras decusan para formar las vías nociceptivas ascendentes. Una vez alcanzadas las estructuras subcorticales, se activan las neuronas del tálamo, quienes envían el estímulo hacia la corteza somatosensorial, desencadenando la percepción consciente del dolor y activando el sistema inhibitorio descendente. Para que la modulación nociceptiva se realice, es necesaria la participación de diversas sustancias o neurotransmisores que conectan áreas del SNC especializadas. Por lo tanto, el objetivo de este estudio fue realizar una revisión de la literatura respecto de los mecanismos que participan en los procesos de modulación central del dolor.

SUMMARY: Pain perception results from multiple and dynamic mechanisms in the central nervous system (CNS) and peripheral nervous system that inhibit or facilitate stimulation and nociceptive response. However, neuromodulation is mainly a function of the CNS. Nociceptive stimulus is detected by peripheral neurons receptors that synapse with the secondary afferent neurons of the spinal cord. These fibers cross to conform the ascending nociceptive pathways. Once the subcortical structures are reached, the thalamus`s neurons are activated; the thalamus send the stimulus to the somatosensory cortex, triggering the conscious perception of pain and activating the descending inhibitory system. For the nociceptive modulation to be carried out, the participation of various substances or neurotransmitters that connect specialized CNS areas is necessary. Therefore, the aim of this study was to review the literature regarding the mechanisms involved in central pain modulation processes.

Descripción de las propiedades funcionales del sistema nociceptivo trigeminal en relación con el dolor pulpar / Description of the functional properties of the nociceptive trigeminal system in relation to pulpal pain

El sistema trigeminal nociceptivo es un componente del sistema sensorial somestésico que tiene la capacidad de discriminar cuatro variables básicas de los estímulos que provocan daño tisular, ellas son: cualidad, curso temporal, localización e intensidad. Las fibras A delta y C, vinculadas a la nocicepción están presentes en la pulpa dental. Se utilizan varias clasificaciones del dolor, atendiendo a diversos criterios: calidad de la sensación, velocidad de transmisión por las fibras, en relación con el lugar del cuerpo donde se exprese, y a la ubicación del nociceptor. La evolución de las condiciones pulpares se clasifican como: pulpitis reversible, pulpitis transicional, pulpitis irreversible y pulpa necrótica.Según su cualidad, el dolor pulpar puede ser punzante o continuo; atendiendo a su aparición, provocado o espontáneo; por su curso, intermitente o continuo; por su localización puede ser limitado a una región, irradiado y referido; y en relación con su intensidad se considera leve, moderado o severo. La capacidad del sistema sensorial nociceptivo en cuanto a discriminar la modalidad, curso temporal, localización e intensidad del estímulo, permite conocer las diferentes etapas de un proceso inflamatorio pulpar(AU)

The nociceptive trigeminal system is a component of the somatosensory system capable of distinguishing four basic variables of stimuli causing tissue damage: quality, time course, location and intensity. A-delta and C fibers, which are related to nociception, are present in dental pulp. Several classifications of pain are used, based on various criteria: quality of the sensation, transmission velocity along fibers, body part where it is expressed, and location of the nociceptor. According to their evolution, pulpal conditions are classified into reversible pulpitis, transitional pulpitis, irreversible pulpitis and necrotic pulp. Pulpal pain has been classified according to the following variables: quality: sharp or continuous; cause: provoked or spontaneous; course: intermittent or continuous; location: limited to a region, radiating or referred; and intensity: mild, moderate or severe. The capacity of the nociceptive sensory system to distinguish the mode, time course, location and intensity of the stimulus makes it possible to recognize the different stages of a pulpal inflammatory process(AU)

Increased multiple sclerosis relapses related to lower prevalence of pain / Aumento nos surtos de esclerose múltipla relacionado com menor prevalência de dor

Objective The study aims to investigate the presence of pain amongst multiple sclerosis (MS) patients. Method One hundred MS patients responded to questionnaires evaluating neuropathic and nociceptive pain, depression and anxiety. Statistical analysis was performed using the Mann–Whitney U, Chi-Square and two-tailed Fisher’s exact tests and multivariate logistic regression. Results Women had a statistically higher prevalence of pain (p = 0.037), and chances of having pain after the age of 50 reduced. Women with pain had a statistically significant lower number of relapses (p = 0.003), restricting analysis to those patients with more than one relapse. After the second relapse, each relapse reduced the chance of having pain by 46%. Presence of pain was independent of Expanded Disability Status Scale (EDSS) anxiety, and depression. Conclusion Our findings suggest a strong inverse association between relapses and pain indicating a possible protective role of focal inflammation in the control of pain. .

Objetivo O estudo tem como objetivo investigar a presença de dor entre pacientes com esclerose múltipla (EM). Método Cem pacientes com EM responderam a questionários avaliando dor neuropática e nociceptiva, depressão e ansiedade. A análise estatística foi realizada através dos testes de Mann-Whitney U, Qui-Quadrado, two tailed Fisher exact test e regressão logística multivariada. Resultados As mulheres apresentaram estatisticamente uma maior prevalência de dor (p = 0,037), e as chances de ter dor após a idade de 50 reduziram. As mulheres com dor tinham um número com significância estatística reduzido de surtos (p = 0,003), restringindo a análise aos pacientes com mais de um surto. Após o segundo surto, cada surto reduziu a chance de ter dor em 46%. A presença de dor foi independente da Expanded Disability Status Scale (EDSS) ansiedade e depressão. Conclusão Nossos resultados sugerem uma forte associação inversa entre o surto e a dor, indicando um possível papel protetor da inflamação focal no controle da dor. .

An interleukin-33/ST2 signaling deficiency reduces overt pain-like behaviors in mice

Interleukin (IL)-33, the most recent member of the IL family of cytokines, signals through the ST2 receptor. IL-33/ST2 signaling mediates antigen challenge-induced mechanical hyperalgesia in the joints and cutaneous tissues of immunized mice. The present study asked whether IL-33/ST2 signaling is relevant to overt pain-like behaviors in mice. Acetic acid and phenyl-p-benzoquinone induced significant writhing responses in wild-type (WT) mice; this overt nociceptive behavior was reduced in ST2-deficient mice. In an antigen-challenge model, ST2-deficient immunized mice had reduced induced flinch and licking overt pain-like behaviors. In the formalin test, ST2-deficient mice also presented reduced flinch and licking responses, compared with WT mice. Naive WT and ST2-deficient mice presented similar responses in the rota-rod, hot plate, and electronic von Frey tests, indicating no impairment of motor function or alteration in basal nociceptive responses. The results demonstrate that IL-33/ST2 signaling is important in the development of overt pain-like behaviors.

Exercise alleviates hypoalgesia and increases the level of calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats

OBJECTIVE: The aim of this study was to evaluate the effects of treadmill training on nociceptive sensitivity and immunoreactivity to calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats. METHODS: Male Wistar rats were divided into three groups: control, diabetic and trained diabetic. Treadmill training was performed for 8 weeks. The blood glucose concentrations and body weight were evaluated 48 h after diabetes induction and every 30 days thereafter. The nociceptive sensitivity was evaluated using the tail-flick apparatus. The animals were then transcardially perfused, and the spinal cords were post-fixed, cryoprotected and sectioned in a cryostat. Immunohistochemistry for calcitonin gene-related peptide analysis was performed on the dorsal horn of the spinal cord. RESULTS: The nociceptive sensitivity analysis revealed that, compared with the control and trained diabetic animals, the latency to tail deflection on the apparatus was longer for the diabetic animals. Optical densitometry demonstrated decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord in diabetic animals, which was reversed by treadmill training. CONCLUSION: We concluded that treadmill training can alleviate nociceptive hypoalgesia and reverse decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord of diabetic animals without pharmacological treatment.