Neuronas participantes en la modalidad sensorial del dolor bucofacial de la periferia hasta el encéfalo / Neurons involved in the sensory modality of orofacial pain from periphery to encephalon

Introducción: El dolor proveniente de cabeza y cuello se vincula a la vía trigeminal, y participan tres neuronas: neurona de primer orden ubicada en ganglio trigeminal; neurona de segundo orden, en el subnúcleo caudal del nervio trigémino; y la neurona de tercer orden que parte de la zona medial del complejo ventrobasal de tálamo y termina en la corteza cerebral. Objetivo: Interpretar que el daño tisular, mediante impulsos nerviosos es transmitido por una cadena de neuronas hasta el encéfalo. Contenido: Las neuronas de primer orden, sus cuerpos neuronales se encuentran ubicados en el ganglio espinal del trigémino, en hueso temporal. En el subnúcleo caudal, se ubican las neuronas de segundo orden que reciben estímulos nociceptivos y de temperatura de la cara y la boca; sus axones se cruzan en la extensión de este subnúcleo, y ascienden contralateralmente, y establecen sinapsis en el tálamo con neuronas de tercer orden. En el encéfalo no hay un único "centro del dolor", las neuronas de tercer orden, terminan en diferentes áreas de la corteza cerebral que se reconocen como "matriz del dolor". Consideraciones finales: Tres conjuntos de neuronas conforman la vía nociceptiva trigeminal, la primera ubicada en el ganglio trigeminal fuera del sistema nervioso central y los otros dos conjuntos neuronales conforman núcleos dentro del mismo(AU)

Introduction: Pain from the head and neck is linked to the trigeminal pathway and three neurons participate: a first-order neuron located in the trigeminal ganglion, a second-order neuron from the subnucleus caudalis of the trigeminal nerve, and a third-order neuron which starts from the medial area of the ventrobasal thalamus complex and ends in the cerebral cortex. Objective: Describe the way in which a chain of neurons transmit tissue damage to the encephalon by means of nerve impulses. Content: In first-order neurons, their neuronal bodies are located in the trigeminal spinal ganglion, in temporal bone. In the subnucleus caudalis, second-order neurons are found which receive nociceptive and temperature stimuli from the face and mouth. Their axons cross over the extension of this subnucleus, ascend contralaterally and establish synapses with third-order neurons in the thalamus. In the encephalon there is not a single "pain center": third-order neurons end in different areas of the cerebral cortex recognized as the "pain matrix". Final considerations: Three sets of neurons make up the trigeminal nociceptive pathway. The first one is located in the trigeminal ganglion outside the central nervous system whereas the other two form nuclei within it(AU)

Analgesic effect of quetiapine in a mouse model of cancer-induced bone pain

BACKGROUND/AIMS: Cancer-induced bone pain (CIBP) is one of the most common pains in patients with advanced neoplasms. Because of treatment-associated side effects, more than half of cancer patients are reported to have inadequate and undermanaged pain control. New mechanism-based therapies must be developed to reduce cancer pain. Quetiapine is a commonly used atypical antipsychotic drug. We report a study of the potential analgesic effects of quetiapine in a mouse model of CIBP and examine the mechanism of bone pain by analyzing the expression of various nociceptors. METHODS: Fifteen male C3H/HeN mice were arbitrarily divided into five groups: control and, CIBP with no treatment, quetiapine treatment, opioid treatment, and melatonin treatment. The mice were tested for mechanical hyperalgesia by determining the nociceptive hind paw withdrawal pressure threshold. Tissues from tibia were removed and subjected to quantitative and qualitative evaluations of transient receptor potential vanilloid 1 (TRPV1), TRPV4, acid-sensing ion channel 1 (ASIC1), ASIC2, and ASIC3 expression. RESULTS: Paw withdrawal pressure threshold was improved in the quetiapine treatment group compared with the CIBP group. Expression of TRPV1, TRPV4, ASIC1, ASIC2, and ASIC3 in the CIBP with quetiapine treatment group was significantly lower than that in the CIBP group. CONCLUSIONS: Our results suggest an analgesic effect of quetiapine in the CIBP animal model and implicate TRPV and ASICs as potential targets for cancer pain management.

Clinical value of analgesia/nociception index in evaluating analgesic effect during lobectomy performed via video-assisted thoracoscope / 中华麻醉学杂志

Objective To primarily investigate the clinical value of analgesia/nociception index (ANI) in evaluating the analgesic effect during lobectomy performed via video-assisted thoracoscope.Methods Forty ASA physical status Ⅰ or Ⅱ patients,aged 25-64 yr,weighing 45-80 kg,undergoing elective lobectomy performed via video-assisted thoracoscope,were enrolled in this study.After induction of anesthesia with propofol,sufentanil and cisatracurium,patients received double lumen endotracheal intubation.Anesthesia was maintained with targetcontrolled infusion of propofol,and iv infusion of remifentanil and cisatracurium.The concentration of propofol was adjusted to maintain the bispectral index (BIS) value in the range of 40-60.ANI,HR,systolic blood pressure (SBP),diastolic blood pressure (DBP) and BIS value were recorded within 5 min before and after the predefined time points including posture change between lateral and supine position,ventilatory pattern change between onelung and double-lung ventilation,skin incision and trocars insertion,lymph node dissection and pleural lavage.At skin incision and during trocars insertion,lymph node dissection and pleural lavage,the development of hemodynamic responses (increase in HR and SBP ＞ 20％ of baseline value) were recorded.Results The incidence of hemodynamic responses was 100％ at skin incision and trocars insertion,and 84 ％ during No.4,7,10 groups of lymph node dissection and after pleural lavage and difference was found in ANI during these stimuli.ANI was significantly decreased within 5 min after skin incision,trocars insertion,No.4,7,10 groups of lymph node dissection and pleural lavage than that before the procedures (P ＜ 0.05).The BIS value was maintained at 40-60,and no significant changes were found between before and after the procedures (P ＞ 0.05).No significant changes were found in ANI,HR,SBP,and DBP between before and after the changes of posture and respiratory pattern (P ＞ 0.05).Conclusion ANI can be used to evaluate the analgesic effect during lobectomy performed via video-assisted thoracoscope in patients and is unaffected by the changes of posture and ventilatory pattern.

Pain threshold assessment in relation to neural mobilization therapy / Avaliação do limiar de dor frente à terapia com mobilização neural

Nervous System Mobilization is used to restore the biomechanics of the nervous system and adjacent structures, promoting the return to their duties. This study evaluated the pain threshold to pressure, to cold, and the cold pain intensity in healthy subjects that underwent intervention with neural mobilization. The sample consisted of 20 volunteers with a mean age of 19.5 ± 1.0 years. The participants were divided randomly into two groups: group 1 (G1) and group 2 (G2); the first group received intervention by means of neural mobilization, and the second, by means of conventional stretching exercises, on the first day; on the subsequent day the procedures were reversed for the groups. The volunteers were evaluated using the pain threshold to pressure and to cold, and the cold pain intensity, prior, immediately after, 20, and 40 minutes after the intervention. No significant differences were found between any assessments. In conclusion, the pain threshold to pressure and to cold, and the cold pain intensity had no significantly change after neural mobilization.

A mobilização do Sistema Nervoso é utilizada para restabelecer a biomecânica do sistema nervoso e também de estruturas adjacentes, o que promove o retorno às suas funções. O objetivo do presente estudo foi avaliar o limiar de dor à pressão e ao frio e a intensidade da dor ao frio, em indivíduos saudáveis submetidos à intervenção com mobilização neural. A amostra foi composta por 20 voluntárias, com idade média de 19,5 ± 1,0 anos. As participantes foram divididas, aleatoriamente, em dois grupos, o grupo 1 (G1) e o grupo 2 (G2), sendo que o primeiro recebeu intervenção por meio de mobilização neural e o segundo por meio de alongamentos convencionais, no primeiro dia, já no dia posterior os grupos inverteram os procedimentos. As voluntárias foram avaliadas por meio do limiar de dor à pressão e ao frio, além da intensidade de dor ao frio, antes das intervenções, imediatamente após, 20 e 40 minutos depois das intervenções. Os resultados demonstraram que em todas as avaliações não houve diferenças significantes. Desta maneira concluiu-se que o limiar de dor à pressão e ao frio e a intensidade de dor ao frio não foram alterados significativamente após mobilização neural.

Actividad espontánea de nociceptores cutáneos en pacientes con neuropatía de fibras delgadas / Spontaneous activity of cutaneous nociceptors in patients with painful polyneuropathy. Report of three patients

Background: Painful polyneuropathy may result from selective impairment of small diameter nerve fibers, while tactile and motor functions are preserved. In these patients clinical and electrophysiological assessment is usually unrevealing. We report three patients with a pure painful polyneuropathy. One of them had neurogenic pruritus additionally. Quantitative sensory analysis disclosed a slight warm hypoesthesia (3/3) and paradoxical hot sensation (2/3) in the feet. Intraneural recordings from the peroneal nerve demonstrated abnormal spontaneous activity in 8 of 17 nociceptive afferents. One of them displayed double firing reflecting impulse multiplication. These results support the notion that patients with pain or pruritus with a distal distribution similar to a polyneuropathy, could have small diameter afferent fiber damage, despite normal function of large diameter fibers.

Citocinas e dor: [revisão] / Cytokines and pai: [review]

JUSTIFICATIVA E OBJETIVOS: As citocinas são substâncias necessárias para a resposta inflamatória, favorecendo a cicatrização apropriada da ferida. No entanto, a produção exagerada de citocinas pró-inflamatórias a partir da lesão pode manifestar-se sistemicamente com instabilidade hemodinâmica ou distúrbios metabólicos. O objetivo desta revisão foi descrever os efeitos das citocinas na dor. CONTEÚDO: Este artigo faz uma revisão dos efeitos das citocinas na dor. Em doenças que cursam com processo inflamatório agudo ou crônico, as citocinas podem ser reconhecidas por neurônios e utilizadas para desencadear diversas reações celulares que influenciam na atividade, proliferação e sobrevida da célula imunológica, bem como na produção e atividade de outras citocinas. As citocinas podem ser pró-inflamatórias e anti-inflamatórias. As pró-inflamatórias estão relacionadas com a fisiopatologia das síndromes dolorosas. Foram descritas as células que secretam as citocinas, as citocinas pró-inflamatórias (IL-1, IL-2, IL-6, IL-7 e FNT) e anti-inflamatórias (IL-4, IL-10, IL-13 e FTCβ), as funções de cada citocina e como ocorre a ação dessas substâncias no processamento da dor. CONCLUSÕES: As citocinas desempenham importante papel na dor, agindo através de diferentes mecanismos em vários locais das vias de transmissão da dor.

BACKGROUND AND OBJECTIVES: Cytokines are necessary for the inflammatory response, favoring proper wound healing. However, exaggerated proinflammatory cytokine production can manifest systemically as hemodynamic instability or metabolic derangements. The objective of this review was to describe the effects of cytokines in pain. CONTENTS: This article reviews the effects of cytokines in pain. In diseases with acute or chronic inflammation, cytokines can be recognized by neurons and used to trigger several cell reactions that influence the activity, proliferation, and survival of immune cells, as well as the production and activity of other cytokines. Cytokines can be proinflammatory and anti-inflammatory. Proinflammatory cytokines are related with the pathophysiology of pain syndromes. Cells that secrete proinflammatory (IL-1, IL-2, IL-6, IL-7, and TNF) and anti-inflammatory (IL-4, IL-10, IL-13, and TGFβ) cytokines, the functions of each cytokine, and the action of those compounds on pain processing, have been described. CONCLUSIONS: Cytokines have an important role in pain through different mechanisms in several sites of pain transmission pathways.

JUSTIFICATIVA Y OBJETIVOS: Las citocinas son sustancias necesarias para la respuesta inflamatoria, favoreciendo la cicatrización apropiada de la herida. Sin embargo, la producción exagerada de citocinas proinflamatorias a partir de la lesión puede manifestarse sistémicamente con la inestabilidad hemodinámica o disturbios metabólicos. El objetivo de esta revisión fue describir los efectos de las citocinas en el dolor. CONTENIDO: Este artículo intenta hacer una revisión de los efectos de las citocinas en el dolor. En enfermedades que se manifiestan con un proceso inflamatorio agudo o crónico, las citocinas pueden ser reconocidas por las neuronas y utilizadas para desencadenar diversas reacciones celulares que influyen en la actividad, proliferación y sobrevida de la célula inmunológica, como también en la producción y en la actividad de otras citocinas. Las citocinas pueden ser proinflamatorias y antiinflamatorias. Las proinflamatorias tienen una relación con la fisiopatología de los síndromes dolorosos. Ya se han descrito las células que segregan las citocinas, las citocinas proinflamatorias (IL-1, IL-2, IL-6, IL-7 y FNT) y antiinflamatorias (IL-4, IL-10, IL-13 y FTCβ), las funciones de cada citocina y también cómo ocurre la acción de esas sustancias en el proceso del dolor. CONCLUSIONES: Las citocinas desempeñan un rol muy importante en el dolor, actuando por medio de diferentes mecanismos en varios locales de las vías de transmisión del dolor.

Periosteal nociceptors induced hypotension and bradycardia under spinal anesthesia: A report of two cases / 대한마취과학회지

The sudden hemodynamic disturbance in the perioperative period can occur because of various surgical and anesthetic reasons but hemodynamic collapse due to noxious stimulus of periosteum stripping has not been described. We report two cases of severe hypotension and bradycardia during periosteum stripping in orthopedic surgery under subarachnoid block even though the block level was adequate. In our patients, hemodynamic collapse occurred specifically at a moment when surgeons manipulated periosteum and fall in blood pressure and heart rate was sudden in onset. The hemodynamic disturbance did not appear to be related to vagally mediated or due to blockade of sympathetic fibers but appeared to be related to periosteal nociceptors.

The study on pain evoked potentials in patients with amyotrophic lateral sclerosis / 中华神经科杂志

Objective To study the features of pain evoked potentials in patients with amyotrophic lateral sclemsis(ALS)and evaluate the pain pathway in these patients.Methods Sixty patients with ALS and 60 controls were set on supine position.The contact heat evoked potential stimulator with a diameter of 27 mm and an area of 573 mm2was used to elicit pain and contact heat evoked potentials(CHEP)in an accelerating speed of 70 ℃/s.Thermal stimuli were given at 54.5 ℃ to three body sites:the dorsum of hand,proximal volar for aml and C7. CHEP was recorded at spots of Cz and Pz.The features of CHEP was observed At the same time,somatosensory evoked potential(SEP)was assesed.Results The figure and latency of CHEP in ALS patients were normal.The latency was:the dorsum of hand:(561.2±28.6)ms; proximal volar forarm:(540.1±39.2)ms;C7:(512.7±31.4)ms.There were no significant differences of latency and SEP between tlle ALS patients and the controls((558.7±30.2),(536.6±23.5), (501.8±26.0)ms,t=4.23,4.51,3.74,P＞0.05).Conclusion Patients with ALS have a normal CHEP,suggesting that the pain pathway in patient with ALS is intact.

Bases fisiopatológicas del dolor / Physiopathological bases of the pain

El dolor es un signo de enfermedad y un motivo frecuente de consulta; se clasifica en agudo o crónico, nociceptivo o neuropático, y según la velocidad de conducción en rápido o lento. Los estímulos causantes del dolor son detectados por receptores nociceptores; los cuales son identificados como fibras C y fibras Aδ. El proceso neural de la transmisiσn del dolor comprende: La transducciσn; es el proceso por el cual el estνmulo nociceptivo es convertido en seρal elιctrica en los nociceptores. La transmisiσn; es el proceso por el cual los estímulos nociceptivos son referidos al asta dorsal de la medula espinal, donde se liberan los neurotransmisores del dolor: Glutamato, sustancia P, péptido relacionado al gen de la calcitonina. Seguidamente el estímulo cruza al lado contralateral de la medula espinal y viaja en el haz espinotálamico hasta el tálamo y luego a la corteza cerebral. La modulación; es el proceso por el cual la señal nociceptiva en el asta dorsal de la medula puede ser inhibida y modificada para los centros superiores del dolor. Los opiodes endógenos y exógenos dan lugar a un bloqueo indirecto de los canales de calcio y apertura de los canales de potasio, con hiperpolarización celular e inhibición de la liberación de mediadores del dolor. La activación del sistema neural descendente da lugar a la liberación de b endorfinas, encefalinas, dinorfinas; que alivian el dolor.

Pain is a sign of illness and a common complain that bring patients to a health care facility. It is classified in acute or chronic pain, nociceptive or neuropathic, and according to conduction velocity, fast or slowly. C and Aδ- fibers respond to stimuli and produce the experience of pain, this defines them as nociceptors. Central pathways of pain include: nociceptors respond to stimuli and produce the experience of pain when they are electrically stimulated (Transduction); axons of nociceptors enter the spinal cord via the dorsal root, where Glutamate are Substance P are released, spinal neurons send their axons to the contralateral thalamus (Transmission); the perceived intensity of pain can be modulated by brain circuits (Modulation). Pain inhibition is achieved by calcium channel blockage and open potassium channel by endogenous and exogenous opioids, due hyperpolarization of the cell and inhibition of pain mediators. b endorphins, enkephalins and dinorphins are released due to activation of neural descending pathway causing pain relief.

The Chemical Markers of Plant Lectin B4 in the Enteric Nervous System of Mice / 医学研究杂志

Objective To investigate the relationship of the chemical coding enteric nervous system of the mice and expression for neurotransmittor of enteric primary afferent neurons for Nociceptors.Methods Immunocytochemical and morphometric techniques were used to quantify the distribution of IB4-containing neurons in mice enteric nervous system using three mice chiocing every vision 50 neurons undering confocal microscopy IB4 immunolabelling and colocalized with calretinin and lectin B4.Results IB4 being binded to primary afferent neurons of enteric pleuxes happend in small intestin and colon of mice,where it was selective for nociceptive neurons.IB4 revealed large round or oval(Dogiel type II)neurons,type I neurons with prominent laminar dendrites and small neurons of myenteric ganglia.The type II neurons were immunoreactive for calretinin,and some type I neurons were immunoreactive for nitric oxide synthase.Most neurons in the submucosal ganglia bound IB4,and some of these were vasoactive intestinal peptide immunoreactive.Conclusion The results indicate that IB4 labels specific subgroups of enteric neurons in the enteric nervous system of the mice.These include intrinsic primary afferent neurons,but other neurons,including secretomotor neurons,are labeled.The results suggest that IB4 is not a specific label for enteric nociceptive neurons.

Effects of Different Concentrations of Formalin on Paw Edema and Pain Behaviors in Rats

The aim of this study was to determine whether formalin reliably provokes a paw edema and pain behavior. The paw of male Sprague-Dawley rats were injected with 100 microliter of formalin with 2.5% (F2.5), 5% (F5), and 10% (F10) concentrations. Following the formalin (n=8) or saline (control, n=6) injection, the flinching or licking of the paw was recorded for the phase 1 response (0-5 min after injection) and phase 2 response (20-60 min). The formalin-induced paw edema was assessed by measuring the diameters of the injected paws at 4 hr after injection. As for flinching, phase 1 and 2 of all three groups showed higher frequency than those of the control group (p<0.05). As for licking, phase 1 cumulative time of the F2.5 and F10 groups, and phase 2 cumulative time of the F2.5 and F5 groups showed a longer duration than those in the control group (p<0.05). The diameters of the paw in the F10 group were significantly larger than those in the control group (p<0.05). Flinching behavior was more reliably expressed the biphasic response than licking response at all formalin concentrations. Peak of the licking was reached at 2.5% and that of flinching was reached at 5%, whereas the paw edema peaked at 10% concentration. This suggests that there may be some dissociation of nociception from the edema formation.

Nuevo enfoque de la interpretación del dolor en una pulpitis aguda

El dolor es probablemente el principal motivo de consulta en las urgencias estomatológicas y es precisamente el dolor de la pulpitis aguda el que comentamos en este trabajo. El dolor pulpar en sí mismo es similar al dolor que resulta por inflamación de los órganos viscerales y, por lo tanto, podrían ser inadecuados los intentos de explicarlos por comparación con los nociceptores de estructuras somáticas. Se propone analizar el comportamiento del dolor como consecuencia de una pulpitis aguda, con un nuevo enfoque, asimilándolo como el dolor proveniente de estructuras viscerales con manifestaciones dolorosas alejadas del sitio o zona dañada y en el propio diente en que el tejido ha sido injuriado y evoluciona rápidamente hacia la necrosis. Establecemos una analogía entre el dolor visceral como el generado de la pulpa y el del tipo somático profundo como el correspondiente a la afectación periapical por rápida evolución de la inflamación hacia la necrosis.

Pain is probably the chief complaint in dental emergencies and this paper deals precisely with the pain caused by acute pulpitis. The pulpar pain itself is similar to the one resulting from inflammation of the visceral organs and, therefore, the attempts to explain these pains by comparing them with the nociceptors of somatic structures may be inappropiate. It is our objective to analyze the behaviour of pain caused by acute pulpitis with a new approach, assimilating it as the pain from visceral structures with painful manifestations far from the damaged site or zone and it is the own tooth whose tissue has been affected and evolves rapidly to necrosis.We establish an analogy between the visceral pain as the one generated by the pulpa and that of deep somatic type as the corresponding to the periapical affection by the fast evolution of inflammation to necrosis.

The Alterations of Unit Discharges of Hippocampal Formation in Acupuncture Analgesia / 第三军医大学学报

The actions of the hippocampal formation were studied by recording the electrical activities of a single neuron of that area. Two different reactions of some neurons in CAl, CA2 and the dentate gyrus might occur after peripheral noxious stimulations, that is, the increasing of the reaction frequency of the nociceptive excited neurons(NEN) and the decreasing of the reaction frequency of the nociceptive inhibited neurons (NIN). Electrical acupuncture of the "points" would result in inhibiting effect on most of the NENs but disinhibiting effect on NINs, Identical effect to that of acupuncture could be created by injecting morphine to the experimental animals. Electrical stimulation of the nucleus raphe magnus or para-aqueduct gray matter(PAG) could affect the NENs and NINs in the hippocampus, and the results were similar to that of acupuncture. When 5-HT was injected into the lateral ventricle or applied to the hippocampal neurons through micro-iontophoresis, effects similar to that of acupuncture also occurred. These facts imply that the effects of peripheral "point" acupuncture on the electrical activities of the neurons of the hippocampal formation might be related to the activities of the endogenous 5-HTergic neurons, or to the endogenous morphine-like substance. The NENs would be inhibited after large amounts of GABA were injected into the lateral ventricle. The inter-relationship between this phenomenon and the activities of GABAergic interneu.rons in the hippocampus awaits further investigation.