Guia prático para o manejo da dor / Guia prático para o manejo da dor

O estudo da dor e suas particularidades é de grande importância para o tratamento de diversas patologias e para a melhora na qualidade de vida dos pacientes. A maioria das disfunções orgânicas tem a dor como um ponto importante da sua manifestação. Dessa maneira, é justificável a elaboração de conteúdo para auxiliar os profissionais da saúde no entendimento e tratamento das principais causas de dores agudas e crônicas. Este livro foi elaborado com o objetivo de servir como um guia prático para o manejo da dor por profissionais e acadêmicos de Medicina. Engloba temas como conceitos e aspectos biopsicossociais da dor, além de questões mais complexas como a fisiologia da dor e o tratamento medicamentoso com o arsenal terapêutico existente. Finalmente, também trata dos diversos tipos de dor mais prevalentes e o conhecimento básico que envolve seu manejo.

Role of neuron and non-neuronal cell communication in persistent orofacial pain

It is well known that trigeminal nerve injury causes hyperexcitability in trigeminal ganglion neurons, which become sensitized. Long after trigeminal nerve damage, trigeminal spinal subnucleus caudalis and upper cervical spinal cord (C1/C2) nociceptive neurons become hyperactive and are sensitized, resulting in persistent orofacial pain. Communication between neurons and non-neuronal cells is believed to be involved in these mechanisms. In this article, the authors highlight several lines of evidence that neuron-glial cell and neuron macrophage communication have essential roles in persistent orofacial pain mechanisms associated with trigeminal nerve injury and/or orofacial inflammation.

Depolarizing Effectors of Bradykinin Signaling in Nociceptor Excitation in Pain Perception

Inflammation is one of the main causes of pathologic pain. Knowledge of the molecular links between inflammatory signals and pain-mediating neuronal signals is essential for understanding the mechanisms behind pain exacerbation. Some inflammatory mediators directly modulate the excitability of pain-mediating neurons by contacting the receptor molecules expressed in those neurons. For decades, many discoveries have accumulated regarding intraneuronal signals from receptor activation through electrical depolarization for bradykinin, a major inflammatory mediator that is able to both excite and sensitize pain-mediating nociceptor neurons. Here, we focus on the final effectors of depolarization, the neuronal ion channels, whose functionalities are specifically affected by bradykinin stimulation. Particular G-protein coupled signaling cascades specialized for each specific depolarizer ion channels are summarized. Some of these ion channels not only serve as downstream effectors but also play critical roles in relaying specific pain modalities such as thermal or mechanical pain. Accordingly, specific pain phenotypes altered by bradykinin stimulation are also discussed. Some members of the effector ion channels are both activated and sensitized by bradykinin-induced neuronal signaling, while others only sensitized or inhibited, which are also introduced. The present overview of the effect of bradykinin on nociceptor neuronal excitability at the molecular level may contribute to better understanding of an important aspect of inflammatory pain and help future design of further research on the components involved and pain modulating strategies.

Orexin-A inhibits capsaicin-induced changes in cyclooxygenase-2 and brain-derived neurotrophic factor expression in trigeminal nucleus caudalis of rats

BACKGROUND: The trigeminal nucleus caudalis (Vc) is a primary central site for trigeminal transmitting. Noxious stimulation of the trigeminal nociceptors alters the central synaptic releases and neural expression of some inflammatory and trophic agents. Orexin-A and the orexin 1 receptor (OX1R) are expressed in pain pathways including trigeminal pain transmission. However, the the mechanism(s) underling orexin-A effects on trigeminal pain modulation have not been fully clarified. METHODS: Trigeminal pain was induced by subcutaneous injection of capsaicin in the upper lip in rats. The effect of trigeminal pain on cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) expression in the Vc of animals was determined by immunofluorescence. Subsequently, OX1R agonist (orexin-A) and antagonist (SB-334867-A) was administrated in the Vc to investigate the possible roles of the Vc OX1R on changes in COX-2 and BDNF levels following pain induction. RESULTS: The data indicated an increase in COX-2 and decrease in BDNF immuno-reactivity in the Vc of capsaicin, and capsaicin- pretreated with SB-334867-A (80 nM), groups of rat. However, the effect of capsaicin on COX-2 and BDNF expressions was reversed by a Vc microinjection of orexin-A (100 pM). CONCLUSIONS: Overall, the present data reveals that orexin-A can attenuate capsaicin-induced trigeminal pain through the modulation of pain effects on COX-2 and BDNF expressions in the Vc of rats.

Participation of central GABAA receptors in the trigeminal processing of mechanical allodynia in rats

Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta (IL-1β) (1 ng/10 µL) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A (GABAA) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions. However, intracisternal administration of bicuculline (50 ng) produced a paradoxical anti-allodynic effect under inflammatory pain conditions. Pretreatment with resiniferatoxin (RTX), which depletes capsaicin receptor protein in primary afferent fibers, did not alter the paradoxical anti-allodynic effects produced by the intracisternal injection of bicuculline. Intracisternal injection of bumetanide, an Na-K-Cl cotransporter (NKCC 1) inhibitor, reversed the IL-1β-induced mechanical allodynia. In the control group, application of GABA (100 µM) or muscimol (3 µM) led to membrane hyperpolarization in gramicidin perforated current clamp mode. However, in some neurons, application of GABA or muscimol led to membrane depolarization in the IL-1β-treated rats. These results suggest that some large myelinated Aβ fibers gain access to the nociceptive system and elicit pain sensation via GABA(A) receptors under inflammatory pain conditions.

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.

Activation of C-fiber nociceptors by low-power diode laser / Ativação por laser de diodo de baixa potência de nociceptores relacionados a fibras C

ABSTRACT Objective The evaluation of selective activation of C-fibers to record evoked potentials using the association of low-power diode laser (810 nm), tiny-area stimulation and skin-blackening. Method Laser-evoked potentials (LEPs) were obtained from 20 healthy young subjects. An aluminum plate with one thin hole was attached to the laser probe to provide tiny-area stimulation of the hand dorsum and the stimulated area was covered with black ink. Results The mean intensity used for eliciting the ultra-late laser-evoked potential (ULEP) was 70 ± 32 mW. All subjects showed a clear biphasic potential that comprised a negative peak (806 ± 61 ms) and a positive deflection (1033 ± 60 ms), corresponding to the ULEP related to C-fiber activation. Conclusion C-fiber-evoked responses can be obtained using a very low-power diode laser when stimulation is applied to tiny areas of darkened skin. This strategy offers a non-invasive and easy methodology that minimizes damage to the tissue.

RESUMO Objetivo Avaliação da ativação de fibras C para o registro de potenciais evocados utilizando-se laser de baixa potência, áreas pequenas de estimulação e escurecimento da pele. Método Potenciais evocados foram obtidos de 20 sujeitos. Uma placa de alumínio com uma pequena abertura foi acoplada à ponteira do laser para estimular área escurecida do dorso da mão. Resultados A intensidade média utilizada para estimulação foi de 70 ± 32 mW. Todos os sujeitos apresentaram respostas claras compreendendo dois picos um negativo (806 ± 61 ms) seguido por outro positivo (1033 ± 60 ms), correspondendo ao potencial evocado tardio por estimulação de fibras C. Conclusão Respostas de fibras C podem ser obtidas utilizando-se laser de baixa potência quando a estimulação é aplicada a pequenas áreas de pele escurecida. Esta estratégia oferece uma metodologia não invasiva que minimiza danos teciduais.

Temperature Distributions of the Lumbar Intervertebral Disc during Laser Annuloplasty : A Cadaveric Study

OBJECTIVE: Low back pain, caused intervertebral disc degeneration has been treated by thermal annuloplasty procedure, which is a non-surgical treatement. The theoretical backgrounds of the annuloplasty are thermal destruct of nociceptor and denaturization of collagen fiber to induce contraction, to shrink annulus and thus enhancing stability. This study is about temperature and its distribution during thermal annuloplasty using 1414 nm Nd : YAG laser. METHODS: Thermal annuloplasty was performed on fresh human cadaveric lumbar spine with 20 intact intervertebral discs in a 37℃ circulating water bath using newly developed 1414 nm Nd : YAG laser. Five thermocouples were attached to different locations on the disc, and at the same time, temperature during annuloplasty was measured and analyzed. RESULTS: Thermal probe's temperature was higher in locations closer to laser fiber tip and on lateral locations, rather than the in depth locations. In accordance with the laser fiber tip and the depth, temperatures above 45.0℃ was measured in 3.0 mm depth which trigger nociceptive ablation in 16 levels (80%), in accordance with the laser fiber end tip and laterality, every measurement had above 45.0℃, and also was measured temperature over 60.0℃, which can trigger collagen denaturation at 16 levels (80%). CONCLUSION: When thermal annuloplasty is needed in a selective lesion, annuloplasty using a 1414 nm Nd : YAG laser can be one of the treatment options.

Efeito da toxina botulínica tipo A sobre a expressão de neuropeptídeos e o transporte mucociliar nasal em coelhos / Effect of botulinum toxin type A on nasal neuropeptides and mucociliary clearance in rabbits

INTRODUÇÃO: A toxina botulínica tipo A (TXB-A) tem sido testada no tratamento da rinite, principalmente nos casos de rinite idiopática. Sugere-se que um estado de hiper-reatividade do nervo trigêmeo esteja envolvido na fisiopatologia da rinite idiopática. O nervo trigêmeo possui fibras sensitivas não mielinizadas tipo C (FSNMT-C) que contém os neuropeptídeos substância P (SP) e peptídeo relacionado ao gene da calcitonina (CGRP). O óxido nítrico (NO) produzido pelas enzimas óxido nítrico sintase (NOS) também está envolvido nesse processo de neurorregulação nasal. O transporte mucociliar, mecanismo primário de defesa do sistema respiratório, é formado pelo batimento ciliar e muco nasal, e esses componentes podem ser influenciados por diferentes neuropeptídeos e neurotransmissores presentes na mucosa nasal. OBJETIVO: O objetivo deste estudo foi avaliar o efeito da TXB-A sobre a expressão da SP, CGRP e óxido nítrico sintase neural (nNOS), além de sua influência sobre o transporte mucociliar nasal em coelhos. MÉTODOS: Coelhos machos saudáveis da linhagem Nova Zelândia foram divididos em dois grupos: o grupo tratamento recebeu TXB-A (25UI) na concha nasomaxilar (CNM) do lado direito e soro fisiológico a 0,9% (SF0,9%) na CNM esquerda. O grupo controle recebeu SF0,9% na CNM direita e nenhuma intervenção na CNM esquerda. Foram investigados os efeitos da TXB-A sobre a expressão da SP, CGRP e nNOS no tecido de CNM por meio da imuno-histoquímica. Para esta análise, dividiu-se o tecido em camada externa (CE, acima da membrana basal) e camada interna (CI, abaixo da membrana basal). Avaliou-se também a presença de apoptose celular, a frequência de batimento ciliar (FBC), o perfil histoquímico do muco nasal (glicoproteínas ácidas e neutras) e a espessura do epitélio (ESP-CE). RESULTADOS: Foi observado um aumento significativo na quantidade de células apoptóticas na CNM do grupo tratamento que recebeu TXB-A em comparação aos controles (p <= 0,001). A CNM do grupo tratamento...(au)

INTRODUCTION: Botulinum toxin type A (BoNT-A) has been assessed in the treatment of rhinitis, especially in cases of idiopathic rhinitis. Trigeminal hyper-responsiveness appears to be involved in the pathological process of idiopathic rhinitis. Trigeminal nociceptive type C unmyelinated sensory fibers contain the neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP). Nitric oxide (NO) produced by the enzyme nitric oxide synthase (NOS) are also involved in this nasal neurorregulation process. The mucociliary clearance, primary defense system of the respiratory system, is composed by the ciliary beat and nasal mucus. These components can be influenced by different nasal neuropeptides and neurotransmitters. OBJECTIVE: The aim of this study was to evaluate the effect of BoNT-A on the expression of SP, CGRP and neural nitric oxide synthase (nNOS), and its influence on nasal mucociliary clearance in rabbits. METHODS: Healthy New Zealand male rabbits were divided into two groups: the treatment group was challenged with BoNT-A (25UI) in the right nasomaxillary turbinate (NMT) and saline (SF0.9%) in the left NMT. The control group received SF0.9% in the right NMT and no-intervention in the left NMT. We investigated the effects of BoNT-A on SP, CGRP and nNOS expression in the NMT tissue by immunohistochemistry. Each area of interest was subdivided into an internal layer (IL: below the basement membrane) and outer layer (OL: above the basement membrane) for analysis. It was also assessed signs of cellular apoptosis, ciliary beat frequency (CBF), mucus histochemical profile (acidic and neutral glycoproteins) and epithelial thickness (EP-TH). RESULTS: It was observed a significant increase in the amount of apoptotic cells in the BoNT-A-challanged NMT compared with controls (p <= 0.001). The NMT of treatment group which received only SF0.9% showed an increase in the amount of apoptotic cells in the IL compared with controls (NMT SF0.9%, p = 0.035)...

The central mechanisms underlying the phenomenon of acupoint sensitization evoked by visceral nociceptive afferent / 中国针灸

The physiological mechanism underlying the acupoint sensitization was evaluated systemically by using the method of electric physiology at spinal cord, medulla, and thalamus levels; the dynamic change of acupoint from the relative "silence" to the relative "activation" function was explained through the study on the dynamic process of acupoint sensitization; the biological process of the therapeutic effect of acupoint stimulation was illuminated through the research of the central mechanism underlining the dose effect relationship between the sensitive acupoint and the related brain area, thus scientific evidence for the functional link between the acupoint and internal organs as well as the nature of the acupoint were provided.

Expression of Pain Receptors by Arthritis Treatment in Collagen Induced Murine Model of Rheumatoid Arthritis

OBJECTIVE: Rheumatoid arthritis, the most common form of arthritis, is typically characterized by induced inflammatory pain in joints. Recent studies have reported on the expression of pain receptors such as transient receptor potential vanilloid 1 (TRPV1) and acid sensing ion channel 3 (ASIC3), which are related to pain induction and regulation. This study was conducted to investigate the expression of TRPV1 and ASIC3 in response to the analgesic effect of an arthritis treatment in a collagen-induced arthritis (CIA). METHODS: Mice were divided into 3 groups: Control, CIA, and CIA with arthritis treatment. Mice received intraperitoneal injection with 10 mg/kg infliximab and 10 mg/kg meloxicam five times per week for 3 weeks. Mechanical hyperalgesia, histologic examination of the feet, serum levels of inflammatory cytokine such as interleukin-6 (IL-6), and interleukin-17 (IL-17), TRPV1 and ASIC3 expression were investigated. RESULTS: The serum levels of IL-6 and IL-17 were lower in the treatment group (73.77+/-10.11 pg/mL and 26.75+/-7.17 pg/mL, respectively) compared to the CIA group (p<0.001). Histological analysis showed decreased synovial cell proliferation, leukocyte infiltration, and cartilage destruction in the treatment group compared with the CIA group. The CIA group that underwent arthritis treatment showed a significantly increased withdrawal threshold of mechanical nociception on the hind paw and increased expression of TRPV1 and ASIC3 compared to the CIA group. CONCLUSION: Arthritis treatment resulted in an anti-inflammatory and analgesic effect through upregulation of the activity of TRPV1 and ASIC3 in CIA mice.

TWIK-Related Spinal Cord K+ Channel Expression Is Increased in the Spinal Dorsal Horn after Spinal Nerve Ligation

PURPOSE: The TWIK-related spinal cord K+ channel (TRESK) has recently been discovered and plays an important role in nociceptor excitability in the pain pathway. Because there have been no reports on the TRESK expression or its function in the dorsal horn of the spinal cord in neuropathic pain, we analyzed TRESK expression in the spinal dorsal horn in a spinal nerve ligation (SNL) model. MATERIALS AND METHODS: We established a SNL mouse model by using the L5-6 spinal nerves ligation. We used real-time polymerase chain reaction and immunohistochemistry to investigate TRESK expression in the dorsal horn and L5 dorsal rot ganglion (DRG). RESULTS: The SNL group showed significantly higher expression of TRESK in the ipsilateral dorsal horn under pain, but low expression in L5 DRG. Double immunofluorescence staining revealed that immunoreactivity of TRESK was mostly restricted in neuronal cells, and that synapse markers GAD67 and VGlut2 appeared to be associated with TRESK expression. We were unable to find a significant association between TRESK and calcineurin by double immunofluorescence. CONCLUSION: TRESK in spinal cord neurons may contribute to the development of neuropathic pain following injury.

Comparison of membrane electrical properties of somatic nociceptive and non-nociceptive neurons of the anterior cingulate gyrus in cats / 生理学报

Using intracellular potential recording technique in vivo, a series of hyperpolarizing and depolarizing currents at different intensities with a 50-ms duration were injected to somatic nociceptive neurons (SNNs) and somatic non-nociceptive neurons (SNNNs) in the anterior cingulate gyrus (ACG) of cats. The membrane electrical responses of the neurons were recorded, and the membrane electrical parameters of the neurons were calculated for comparative study on membrane electrical properties of SNNs and SNNNs of the ACG. A total of 188 ACG neurons from 57 cats were recorded. Among the 188 neurons, 172 (91.5%) and 16 (8.5%) were SNNs and SNNNs, respectively. The I-V curves of SNNs and SNNNs in the ACG were "S" shapes. When the absolute value of injected current intensity was less than or equal to 1 nA (≤ 1 nA), the I and V of I-V curves of both SNNs and SNNNs were linearly correlated (rSNNs = 0.99, rSNNNs = 0.99). When the absolute value of injected current intensity was more than 1 nA, both SNNs and SNNNs showed a certain inward or outward rectification behavior. Compared with SNNNs, SNNs had stronger rectification and lower adaptability (P < 0.01). With the increase of injected current intensity, the changes of frequency of discharges of SNNs were higher than those of SNNNs. In addition, the membrane resistance (Rm), the membrane capacity (Cm) and the time constant (τ) of SNNs were larger than those of SNNNs (P < 0.05 or P < 0.01). The differences in the membrane electrical properties between SNNs and SNNNs in the ACG suggested the disparity in neuronal cell size and cell membrane structure between them. The results of this study provided the experimental basis for deeply elucidating the mechanisms of somatic nociceptive sensation and characteristics on the membrane electrical aspects of ACG neurons.

El abordaje homeopático de la tos / The homeopathic approach cough

El organismo humano posee distintos mecanismos de defensa natural para sus diversos sistemas, los que son conocidos como signos clínicos o lo que Hahnemann llamaba en los §6 y 7 del Organon la expresión de la fuerza vital. La tos es un fenómeno producido por un mecanismo reflejo que emerge en los receptores vagales situados a lo largo del tracto respiratorio. Se han descrito tres tipos diferentes de receptores, los receptores de estiramiento de adaptación lenta (REAL), receptores de estiramiento de adaptación rápida (REAR) y las fibras C. Este reflejo tusígeno consiste en tres fases: inspiratoria, compresiva y espiratoria. Es importante tener muy en cuenta que la tos es tan sólo un síntoma de un cuadro clínico complejo e individual que se desarrolla en la totalidad del organismo. Incluso la medicina convencional reconoce que la tos, aunque puede ser un síntoma problemático, es una forma de curación del cuerpo; en este sentido, se debe hacer lo posible por no erradicarla, menos aún en menores de seis años, a través de antitusígenos de venta libre.

Human organism has different natural defense mechanisms for its various systems,these mechanisms are known as clinical signs or what Hahnemann called in § 6and 7 of Organon “expression of the vital force”. Cough is a phenomenon caused by a reflection mechanism emerges vagal receptors along the respiratory tract have been described three types of receptors, slowly adapting stretch receptors (SARs), rapidly adapting stretch receptors (RARs) and C-fibers. This cough reflex consists of three phases, the first “inspiratory”, “compression” and “expiratory”. It is important to bear in mind that the cough is just a symptom of a complex clinical picture and individual that develops in the whole organism, even conventional medicine recognizes that cough, but can be a troubling symptom, it is a form of healing the body, in this regard, it should be possible not eradicate it, even less in children under six years antitussives through counter.

The Role of Protease Activated Receptors and Proteases in Subtly Inflamed Diarrhea-Predominant Irritable Bowel Syndrome / 대한소화기학회지

No abstract available.

A aspirina, os opiáceos e a maconha no sistema endógeno de controle da dor / Aspirin, opiates and marijuana in the system of endogenous pain control

Tradução de Diego Molina e revisão do Prof. Dr. Luiz Roberto Giorgetti de Britto. O original em espanhol - "La aspirina, los opioides y la marijuana en el sistema endógeno de control del dolor" - encontra-se à disposição do leitor no Instituto de Estudos Avançados da USP para eventual consulta.

P2X3, but not P2X1, receptors mediate ATP-activated current in neurons innervating tooth-pulp / 华中科技大学学报（医学）（英德文版）

We developed a method that allows us to label nociceptive neurons innervating tooth-pulp in rat trigeminal ganglion neurons using a retrograde fluorescence-tracing method, to record ATP-activated current in freshly isolated fluorescence-labeled neurons and to conduct single cell immunohistochemical staining for P2X1 and P2X3 subunits in the same neuron. Three types of ATP-activated current in these neurons (F, I and S) were recorded. The cells exhibiting the type F current mainly showed positive staining for P2X3, but negative staining for P2X1. The results provide direct and convincing evidence at the level of single native nociceptive neurons for correlation of the characteristics of ATP-activated currents with their composition of P2X1 and P2X3 subunits and cell size. The results also suggest that the P2X3, but not P2X1, is the main subunit that mediates the fast ATP-activated current in nociceptive neurons.

Descending modulation of cardiac nociception by the rostral ventromedial medulla in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the descending modulation of cardiac nociception by the rostral ventromedial medulla (RVM) in rats.</p><p><b>METHODS</b>A rat model of cardiosomatic motor reflex (CMR) was established by injecting capsaicin into the pericardial sac to induce cardiac nociception, and the electromyogram (EMG) response of the dorsal spinotrapezius muscle was studied. The RVM was electrically stimulated (25, 75 and 100 µA) or destroyed to examine whether RVM exerted descending modulation on cardiac nociception.</p><p><b>RESULTS</b>Electrical stimulation of the RVM at 8 sites produced intensity-dependent inhibition of EMG responses to noxious cardiac stimulus (F[2,21]=43.188, P=0.001). Electrical stimulation at 3 sites caused facilitated EMG responses, but the increased magnitude of the EMG was not dependent on stimulation intensity (F[2,6]=0.884, P=0.461). Stimulation at 11 sites produced biphasic effects: at a low intensity (25 µA), the elicited EMG magnitude was significantly larger than baseline (P<0.05), and at greater intensities (75/100 µA), the stimulation caused suppression of the EMG magnitude to a level significantly lower than the baseline (P<0.05). Electrolytic lesion of the RVM resulted in significantly increased EMG responses compared with the baseline and sham lesion group.</p><p><b>CONCLUSION</b>Cardiac nociception evoked by capsaicin stimulation is subjected to descending biphasic modulation by the RVM, which produces predominantly descending inhibition on heart pain.</p>

The role of HO/CO in the spinal nociception transmission and hyperalgesia of rats induced by formalin / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the role of heme oxygenase and carbon monoxide (HO/CO) in the development of spontaneous pain and hyperalgesia of rats induced by formalin injection.</p><p><b>METHODS</b>Zinc protoporphyrin Znpp (the inhibitor of HO) was intrathecally injected to the rats with formalin inflammatory pain. Hemin (the agonist of HO) was intrathecally injected to the normal rats. The weighted pain scores were used to evaluate the degree of pain response. Thermal withdrawal latency and mechanical withdrawal threshold were observed to assess the degree of thermal hyperalgesia and mechanical allodynia.</p><p><b>RESULTS</b>After the intrathecal injection of Znpp, the weighted pain score obviously reduced in a dose-dependent manner compared with the rats with formalin inflammatory pain. Intrathecal injection of Znpp had no obvious effect on thermal withdrawal latency and mechanical withdrawal threshold in injected feet compared with formalin group. But there was a prolongation in a dose-dependent manner in non injected feet. Intrathecal injection of Hemin to normal rats could shorten the thermal withdrawal latency and reduce the mechanical withdrawal threshold on both sides of hindpaws.</p><p><b>CONCLUSION</b>Intrathecal injection of the HO inhibitor produced prominent inhibition to pain related behavior and thermal and mechanical hyperalgesia induced by formalin injection. Intrathecal injection of HO inductor could induce thermal and mechanical hyperalgesia in normal rats. The results indicated that HO/CO took part in the processes of spinal cord nociceptive information transmission and the development of thermal and mechanical hyperalgesia.</p>