Combination ART-Induced Oxidative/Nitrosative Stress, Neurogenic Inflammation and Cardiac Dysfunction in HIV-1 Transgenic (Tg) Rats: Protection by Mg.

Chronic effects of a combination antiretroviral therapy (cART = tenofovir/emtricitatine + atazanavir/ritonavir) on systemic and cardiac oxidative stress/injury in HIV-1 transgenic (Tg) rats and protection by Mg-supplementation were assessed. cART (low doses) elicited no significant effects in normal rats, but induced time-dependent oxidative/nitrosative stresses: 2.64-fold increased plasma 8-isoprostane, 2.0-fold higher RBC oxidized glutathione (GSSG), 3.2-fold increased plasma 3-nitrotyrosine (NT), and 3-fold elevated basal neutrophil superoxide activity in Tg rats. Increased NT staining occurred within cART-treated HIV-Tg hearts, and significant decreases in cardiac systolic and diastolic contractile function occurred at 12 and 18 weeks. HIV-1 expression alone caused modest levels of oxidative stress and cardiac dysfunction. Significantly, cART caused up to 24% decreases in circulating Mg in HIV-1-Tg rats, associated with elevated renal NT staining, increased creatinine and urea levels, and elevated plasma substance P levels. Strikingly, Mg-supplementation (6-fold) suppressed all oxidative/nitrosative stress indices in the blood, heart and kidney and substantially attenuated contractile dysfunction (>75%) of cART-treated Tg rats. In conclusion, cART caused significant renal and cardiac oxidative/nitrosative stress/injury in Tg-rats, leading to renal Mg wasting and hypomagnesemia, triggering substance P-dependent neurogenic inflammation and cardiac dysfunction. These events were effectively attenuated by Mg-supplementation likely due to its substance P-suppressing and Mg's intrinsic anti-peroxidative/anti-calcium properties.

Fish oil supplementation attenuates neuroinflammation and alleviates depressive-like behavior in rats submitted to repeated lipopolysaccharide.

PURPOSE: Depression is frequently associated with inflammation, whereas omega-3 polyunsaturated fatty acids (PUFAs) primarily found in fish oil possess anti-inflammatory properties. Although converging studies suggest an antidepressant effect of PUFAs, there is limited evidence directly linking the neuro-immune modulating features of PUFAs to the antidepressant actions. METHODS: Therefore, we assessed the effects of fish oil (FO) supplementation on behavioral changes, inflammatory cytokine expression and oxidative reactions in frontal cortex and hippocampus of rats following repeated peripheral immune challenge by lipopolysaccharide (LPS) for 2 weeks (500 µg/kg every other day). RESULTS: Repeated LPS administration induced the rats to a depressive-like state and increased mRNA expression of pro-inflammatory cytokines, including 1L-1ß, 1L-6 and TNF-α, in frontal cortex and hippocampus. FO supplementation attenuated the LPS-induced abnormal behavior and brain inflammatory response. Concurrent with the antidepressant action, FO also reduced LPS-induced oxidative reactions and neural apoptosis in the rat brain, as evidenced by decreased malondialdehyde (MDA) production, increased catalase activities and inhibited pro-apoptotic protein Bax mRNA expression. In addition, FO inhibited activation of NF-κB and iNOS induced by LPS. Interestingly, we found FO suppressed the activation of the inflammasome NLRP3 and ionotropic purinergic receptor P2X7R evoked by LPS, suggesting a potential anti-inflammatory mechanism for PUFAs. Besides, FO also restored the LPS-induced neurochemical disturbance, especially the balance between serotonin and kynurenine branches of tryptophan metabolism, which is tightly associated with depression. CONCLUSIONS: These findings provide novel insights into the antidepressant action of PUFAs and further strengthen the link between inflammation and depression.

Central nervous system mast cells in peripheral inflammatory nociception.

BACKGROUND: Functional aspects of mast cell-neuronal interactions remain poorly understood. Mast cell activation and degranulation can result in the release of powerful pro-inflammatory mediators such as histamine and cytokines. Cerebral dural mast cells have been proposed to modulate meningeal nociceptor activity and be involved in migraine pathophysiology. Little is known about the functional role of spinal cord dural mast cells. In this study, we examine their potential involvement in nociception and synaptic plasticity in superficial spinal dorsal horn. Changes of lower spinal cord dura mast cells and their contribution to hyperalgesia are examined in animal models of peripheral neurogenic and non-neurogenic inflammation. RESULTS: Spinal application of supernatant from activated cultured mast cells induces significant mechanical hyperalgesia and long-term potentiation (LTP) at spinal synapses of C-fibers. Lumbar, thoracic and thalamic preparations are then examined for mast cell number and degranulation status after intraplantar capsaicin and carrageenan. Intradermal capsaicin induces a significant percent increase of lumbar dural mast cells at 3 hours post-administration. Peripheral carrageenan in female rats significantly increases mast cell density in the lumbar dura, but not in thoracic dura or thalamus. Intrathecal administration of the mast cell stabilizer sodium cromoglycate or the spleen tyrosine kinase (Syk) inhibitor BAY-613606 reduce the increased percent degranulation and degranulated cell density of lumbar dural mast cells after capsaicin and carrageenan respectively, without affecting hyperalgesia. CONCLUSION: The results suggest that lumbar dural mast cells may be sufficient but are not necessary for capsaicin or carrageenan-induced hyperalgesia.

Effect of neonatal capsaicin treatment on orthodontic tooth movement in male Sprague-Dawley rats.

INTRODUCTION: In this study, we examined the effect of neonatal administration of capsaicin on the magnitude of orthodontic tooth movement in rats. METHODS: Twelve timed pregnant Sprague-Dawley rats were randomized between the capsaicin group and the vehicle group. The pups received treatment with either capsaicin or vehicle on day 2 of life. Capsaicin treatment has been shown to produce a selective destruction of fine myelinated and unmyelinated Aδ and C sensory nerve fibers, causing an inhibition of the effects from neurogenic inflammation. Tooth-movement experiments began at 12 weeks of age. A mesial tipping force was applied to the maxillary first molar by using a 3-mm length of Sentalloy closed-coil spring (Dentsply GAC Intl, Bohemia, NY) activated from a bonded molar cleat to the maxillary incisors; this appliance delivers a constant tipping force of 50 g. Diastema measurements between the first and second molars were made at 2 and 4 weeks after appliance placement. Measurements were made indirectly from stone models by using a charge-coupled device microscope camera and Optimas 5.2 measurement software (Media Cybernetics, Bethesda, Md). Two-way repeated-measures analysis of variance (ANOVA) was used to analyze the differences between the groups. RESULTS: The capsaicin-treated rats and the controls did not differ in the amount of tooth movement at the collected time points (P >0.05). Similarly, the magnitude of change of tooth movement from 2 to 4 weeks did not differ between the groups (P >0.05). An increase in average diastema size was observed between 2 and 4 weeks after appliance activation in both treatment groups (P <0.0001). CONCLUSIONS: These results suggest that neonatal capsaicin desensitization in the rat does not affect the rate of orthodontic tooth movement after the application of a 50-g tipping force to the maxillary first molar. This might be due in part to the development of compensatory mechanisms in the chronically desensitized rat. Further studies are necessary to determine the reproducibility and histologic characteristics of this treatment.

A peripheral neuroimmune link: glutamate agonists upregulate NMDA NR1 receptor mRNA and protein, vimentin, TNF-alpha, and RANTES in cultured human synoviocytes.

Human primary and clonal synovial cells were incubated with glutamate receptor agonists to assess their modulating influence on glutamate receptors N-methyl-d-aspartate (NMDA) NR1 and NR2 and inflammatory cytokines to determine potential for paracrine or autocrine (neurocrine) upregulation of glutamate receptors, as has been shown for bone and chondrocytes. Clonal SW982 synoviocytes constitutively express vimentin, smooth muscle actin (SMA), and NMDA NR1 and NR2. Coincubation (6 h) with glutamate agonists NMDA (5 microM), and the NMDA NR1 glycine site activator (+/-)1-aminocyclopentane-cis-1,3-dicarboxylic acid (5 muM), significantly increases cellular mRNA and protein levels of glutamate receptors, as well as increasing vimentin, SMA, tumor necrosis factor-alpha, and RANTES (regulated on activation, normal T-cell expressed and secreted), assessed qualitatively and quantitatively with nucleotide amplification, image analysis of immunocytochemical staining, fluorescein-activated cell sorting, Western blotting, and immunoassays. Human primary synovial cells harvested from patients with arthritic conditions also constitutively expressed NMDA NR1 with increases after agonist treatment. Glutamate receptor agonist-induced increases were blocked by the noncompetitive glutamate antagonist MK-801 (8 microg/ml) and NR1 blocking antibody. Coincubation with glutamate agonists and phorbol 12-myristate 13-acetate, a protein kinase C activator, significantly enhanced mean levels of TNF-alpha and RANTES in SW982 cell supernatants compared with incubation with either agent alone. Increases were diminished with protein kinase inhibitor and NR1 blocking antibody. The functional activation of glutamate receptors on human synoviocytes establishes a neurogenic cell signaling link between neurotransmitter glutamate released from nerve terminals and target cells in the joint capsule. The influence of glutamate on subsequent release of cellular proinflammatory mediators in non-neural tissue for activation of downstream immune events supports a peripheral neuroimmune link in arthritis.

Accuracy of hippocampal network activity is disrupted by neuroinflammation: rescue by memantine.

Understanding how the hippocampus processes episodic memory information during neuropathological conditions is important for treatment and prevention applications. Previous data have shown that during chronic neuroinflammation the expression of the plasticity related behaviourally-induced immediate early gene Arc is altered within the CA3 and the dentate gyrus; both of these hippocampal regions show a pronounced increase in activated microglia. Low doses of memantine, a low to moderate affinity open channel uncompetitive N-Methyl-d-aspartate receptor antagonist, reduce neuroinflammation, return Arc expression to control levels and attenuate cognitive deficits induced by lipopolysaccharide. Here we investigate whether neuroinflammation affects the accuracy of information processing in the CA3 and CA1 hippocampal regions and if this is modified by memantine treatment. Using the immediate early gene-based brain-imaging method called cellular analysis of temporal activity by fluorescence in situ hybridization, it is possible to detect primary transcripts at the genomic alleles; this provides exceptional temporal and cellular resolution and facilitates the mapping of neuronal activity. Here, we use this method to compare the neuronal populations activated by two separate experiences in CA1 and CA3 and evaluate the accuracy of information processing during chronic neuroinflammation. Our results show that the CA3 pyramidal neuron activity is not stable between two exposures to the same environment context or two different contexts. CA1 networks, however, do not differ from control conditions. These data suggest that during chronic neuroinflammation, the CA3 networks show a disrupted ability to encode spatial information, and that CA1 neurons can work independently of CA3. Importantly, memantine treatment is able to partially normalize information processing in the hippocampus, suggesting that when given early during the development of the pathology memantine confers neuronal and cognitive protection while indirectly prevents pathological microglial activation.

Anti-inflammatory effects of electronic signal treatment.

Inflammation often plays a key role in the perpetuation of pain. Chronic inflammatory conditions (e.g. osteoarthritis, immune system dysfunction, micro-circulatory disease, painful neuritis, and even heart disease) have increased as baby boomers age. Medicine's current anti-inflammatory choices are NSAIDs and steroids; the value in promoting cure and side effect risks of these medications are unclear and controversial, especially considering individual patient variations. Electricity has continuously been a powerful tool in medicine for thousands of years. All medical professionals are, to some degree, aware of electrotherapy; those who directly use electricity for treatment know of its anti-inflammatory effects. Electronic signal treatment (EST), as an extension of presently available technology, may reasonably have even more anti-inflammatory effects. EST is a digitally produced alternating current sinusoidal electronic signal with associated harmonics to produce theoretically reasonable and/or scientifically documented physiological effects when applied to the human body. These signals are produced by advanced electronics not possible even 10 to 15 years ago. The potential long-lasting anti-inflammatory effects of some electrical currents are based on basic physical and biochemical facts listed in the text below, namely that of stimulating and signaling effective and long-lasting anti-inflammatory effects in nerve and muscle cells. The safety of electrotherapeutic treatments in general and EST in particular has been established through extensive clinical use. The principles of physics have been largely de-emphasized in modern medicine in favor of chemistry. These electrical treatments, a familiar application of physics, thus represent powerful and appropriate elements of physicians' pain care armamentaria in the clinic and possibly for prescription for use at home to improve overall patient care and maintenance of quality of life via low-risk and potentially curative treatments.

Prurito / Pruritus

El prurito es la causa más común de consulta en Dermatología. En el presente articulo se hace una revisión de los estudios más relevantes sobre el prurito y se revisan la fisiopatogenia y la relación con enfermedades de distinto tipo. Es importante recalcar la relación entre el prurito y la respuesta del SNC, en lo que se ha llamado la inflamación neurobiológica. Establecemos una forma racional de enfrentar el prurito tanto desde el punto de vista de laboratorio como de terapéutica.

Pruritus is the most common symptom in dermatology. We present a review of the most relevant studies of pruritus its physiopathology and relations with other types of diseases. It is important to emphasize the relation between pruritus the CNS in what is known as neurobiological. Additionally we. Additionally we propase a rational means of facing pruritus from both laboratory and therapeutic perspectives.

Diphenyl diselenide attenuates acute thermal hyperalgesia and persistent inflammatory and neuropathic pain behavior in mice.

Experiments were designed to address whether diphenyl diselenide (PhSe)(2) has antiallodynic and antihyperalgesic properties. The neuropathic pain was caused by a partial tying (2/3) of sciatic nerve and the inflammatory pain was induced by an intraplantar (i.pl.) injection of 20 microl of Freund's Complete Adjuvant (CFA) in mice. Seven days after sciatic nerve constriction and 24 h after CFA intraplantar (i.pl.) injection, mouse pain threshold was evaluated through tactile allodynia, using Von Frey Hair (VHF) filaments. The acute thermal hyperalgesia was induced by intrathecal (i.t.) injection of glutamate, N-methyl-d-aspartate (NMDA), bradykinin (BK) and prostaglandin E(2) (PGE(2)), and the nociceptive response was assessed using hot-plate test. (PhSe)(2) administered by oral route (p.o.) (10 mg/kg) decreased the paw withdrawal response on the ipsilateral side of the partial sciatic nerve ligation 30 min after drug administration (64+/-7%) and this effect was kept for 1 h after treatment. (PhSe)(2) (10 mg/kg, p.o.) produced a reduction in mechanical allodynia induced by CFA started 30 min after (PhSe)(2) administration (71+/-5%) and this effect was maintained for up 4 h. (PhSe)(2) (0.1-50 mg/kg, p.o.) caused a significant inhibition of glutamate-, NMDA- and BK-(PGE(2))-induced acute thermal hyperalgesia in mice. Together, the present results indicate that (PhSe)(2) produces systemic antiallodynic action when assessed in mechanical stimulus (VHF) in the hindpaw and also attenuates acute thermal hyperalgesia. Thus, this compound might be potentially interesting in the development of new clinically relevant drugs for the management of pain.

The effect of sensory nerve stimulation on sensory nerve function in people with peripheral neuropathy associated with diabetes.

OBJECTIVE: To assess the effect of sensory nerve stimulation in older people with peripheral neuropathy associated with diabetes (DPN). MATERIALS AND METHODS: A randomized, placebo controlled, double blind trial was used to assess the effect of 12 weeks of low frequency sensory nerve stimulation (LF-SNS) in the lower limb [International Patent Application No. PCT/AU2004/001079: 'nerve function and tissue healing' (Z. Khalil)]. Response to capsaicin, basal microvascular blood flow, electric cutaneous threshold and oxygen tension were assessed pre- and post-treatment and between limbs. PARTICIPANTS: People 55 years of age or older diagnosed with DPN: 35 active and 31 placebo participants. RESULTS: Between groups comparisons: no significant differences occurred between stimulation groups. Within subject comparisons: in the active LF-SNS group, comparing stimulated to contralateral legs, there were significant increases in size of capsaicin flare [t(1,33)=3.65, p<0.05] and capillary blood flow [t(1,34)=-0.33, p<0.05]. There was a trend to improvement in time to initial flare response [t(1,34)=-1.86, p=0.07]. No changes were evident in the placebo group. RESPONDER ANALYSES: In a group of 'responders', the time to initial flare response (p<0.05, r=0.64), size of capsaicin flare (p<0.05 r=1.0) and microvascular blood flow (p<0.05, r=0.60) improved significantly after LF-SNS. CONCLUSIONS: The observed data suggest that LF-SNS improves nerve function in a subset of people with DPN. Targeting toward probably 'responders' may deliver the greatest benefit from short-term therapy. Testing optimal application in others seems warranted.

[Mechanisms by which acute orofacial pain becomes chronic]. / Mécanismes de la chronicisation de la douleur oro-faciale aiguë.

Pain is a complex, multidimensional experience encompassing sensory-discriminative, cognitive, emotional and motivational dimensions. These dimensions in the orofacial region have particular expression since the face and mouth have special biological, emotional and psychological meaning to each individual. Orofacial pain is frequent. Epidemiological studies reveal a high prevalence of severe pain in syndromes such as temporomandibular disorders (TMD), burning mouth syndrome and toothaches, as well as an important role of psychosocial influences, contributing to the persistence of these syndromes. Many of the difficulties experienced by clinicians with the diagnosis and management of acute and chronic orofacial pain stem from a lack of recognition and understanding of these complex conditions, the various intricate bio-psycho-social interactions and the neurobiology behind the chronicisation of acute pain. This text strives to review the important advances and insights into the peripheral processes by which noxious stimuli activates or modulates nociceptive afferent input into the brainstem, the neural pathways in the brainstem and higher levels of the trigeminal (V) somatosensory system and the mechanisms involved in the plasticity of nociceptive transmission. We shall link this knowledge to clinical correlates and suggest a therapeutic approach in acute orofacial pain, in the attempt to avoid the development of chronic pain.

Substance P does not play a critical role in neurogenic inflammation in the rat masseter muscle.

In this study, we performed a series of experiments to investigate whether substance P (SP) contributes to neurogenic inflammation in the skeletal muscle tissue. Intramuscular injection of an inflammatory irritant, mustard oil (MO), induces significant edema formation in the rat masseter muscle. In order to study the contribution of endogenous SP in the MO-induced edema, groups of rats were pretreated with two different doses (100 nmol; 1 microl) of either peptidergic (Sendide) or non-peptidergic (L703, 606) neurokinin 1 (NK1) receptor antagonist in one masseter muscle 15 min prior to the MO injection in the same muscle. The extent of edema was assessed as the percent weight difference of the injected muscle compared to the non-injected muscle. Neither Sendide nor L703,606 pretreatment resulted in a significant inhibition of the MO-induced edema in the masseter muscle. Exogenous application of SP also produced a significant swelling of the muscle, which was blocked by L703,606 (1 microl) pretreatment, suggesting that evoked release of SP following MO injection is not sufficient to induce significant edema formation. Capsaicin (1% in 25 microl), which is known to cause neurogenic inflammation, failed to produce edema formation in the masseter muscle. The same concentration of capsaicin injected into the hindpaw produced significant swelling of the injected paw. Taken together, these results provide compelling evidence that, unlike cutaneous or joint tissue, SP does not play a critical role in inducing neurogenic inflammation in the skeletal muscle tissue.

["Sickness behavior"--mechanisms of origin and significance]. / "Sickness Behavior"--mechanizmy powstania i znaczenie.

Psychoneuroimmunology, a combination of immunology and neurobiology, is a new field that has emerged over the past 20 years. There is now overwhelming evidence suggesting that the central nervous system is capable of regulating the immune response via two pathways--the autonomic and the neuroendocrine. It is also well documented that the immune system can influence the central nervous system by regulatory molecules or cytokines produced by activated immune cells. In this way, there is a bi-directional communication pathway between the two systems. Sickness behavior seems to present excellent evidence for the existence of immune-system-brain communication. Nonspecific symptoms of infection and inflammation include not only profound physiological but also behavioral changes. Behavioral changes can include anorexia, adipsia, increased sleepiness and depression in social, sexual exploration and general activity. These behavioral changes triggered by pro-inflammatory cytokines are thought to have evolved to conserve the energy necessary to fight infection. They may also minimize infection of conspecifics and reduce susceptibility to predation. Taken together, sickness behavior represents a behavioral reorganization highly motivated to promote survival and recovery. Knowing the mechanisms of neuroimmunomodulation allow us to better understand both the behavioral changes associated with immunotherapy and the changes in immune activation in major depression and other mental disorders.

Attenuation of knee joint inflammation by peripherally administered endomorphin-1.

Endomorphin-1 is a selective endogenous ligand for the micro-opioid receptor, and this study investigated the effect of endomorphin-1 on rat knee joint inflammation by examining the ability of the neuropeptide to modulate synovial protein extravasation. Acute joint inflammation was induced by intraarticular injection of 2% kaolin followed by 2% carrageenan and the animals allowed to recover for 3 h. Immunohistochemical examination of these inflamed joints revealed endomorphin-1-like immunoreactive nerves in deep synovium with a proportion of the nerve fibers occurring in close proximity to synovial blood vessels. Perfusion of inflamed knees with exogenous endomorphin-1 across the dose range 10-9-10-6 M produced a significant reduction in synovial vascular permeability with the 10-7M dose producing the greatest fall in protein exudation (approx 55%). These effects were blocked by the specific micro-opioid receptor antagonist CTOP. Destruction of knee joint unmyelinated afferent nerve fibers by capsaicin treatment significantly attenuated the anti-inflammatory effects of endomorphin-1, suggesting that the peptide is acting via a neurogenic mechanism. The findings of this study indicate that endomorphin-1 acts peripherally in knee joints to reduce synovial protein extravasation. These anti-inflammatory effects are mediated by micro-opioid receptors located on capsaicin-sensitive afferent nerves.

Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado.

UNLABELLED: This study was designed to determine if the Amazonian medicinal sangre de grado, confers benefit by suppressing the activation of sensory afferent nerves. METHODS: (i) vasorelaxation of rat mesenteric arteries in response to calcitonin gene-related peptide; (ii) rat paw edema in response to protease- activating peptide receptor 2-activating peptide; (iii) rat paw hyperalgesia in response to low-dose protease-activating peptide receptor 2-activating peptide or prostaglandin E2; (iv) gastric hyperemia in response luminal capsaicin; (v) a clinical trial of a sangre de grado balm in pest control workers. The parent botanical was fractionated for evaluation of potential active components. In preconstricted rat mesenteric arteries, highly diluted sangre de grado (1:10,000) caused a shift to the right of the calcitonin gene-related peptide dose-response curve (p < 0.01). Paw edema in response to protease-activating peptide receptor 2-activating peptide (500 microg) was reduced by as single topical administration sangre de grado balm (1% concentration, p < 0.01) for at least 6 h. Hyperalgesia induced by either low-dose protease-activating peptide receptor 2-activating peptide (50 microg) or prostaglandin E2 was prevented by sangre de grado balm. A fraction possessing analgesic and capsaicin antagonistic properties was isolated and high-performance liquid chromatography and gas chromatography-mass spectrometry analysis indicated that it was a proanthocyandin oligomer. In pest control workers, sangre de grado balm (Zangrado) was preferred over placebo, for the relief of itching, pain, discomfort, edema, and redness in response to wasps, fire ants, mosquitoes, bees, cuts, abrasions, and plant reactions. Subjects reported relief within minutes. We conclude that sangre de grado is a potent inhibitor of sensory afferent nerve mechanisms and supports its ethnomedical use for disorders characterized by neurogenic inflammation.

Síndrome dolorosa miofascial: artigo de revisäo / Myofascial pain syndrome: review article

O objetivo deste artigo foi apresentar aspectos da síndrome dolorosa miofascial encontrados na literatura. Além dos conhecidos distúrbios dos tecidos moles, que incluem os efeitos de traumas, as inflamaçöes, fraqueza, tensäo e espasmos musculares, há uma entidade fisiopatológica descrita a alguns anos, que também atinge estes tecidos e é conhecida como síndrome dolorosa miofascial. Esta síndrome é descrita como sendo uma disfunçäo neuromuscular regional caracterizada pela presença de locais sensíveis em bandas musculares contraturadas/tensas que produzem dor referida em áreas distantes ou adjacentes. Inúmeros tratamentos têm sido propostos visando à remissäo do quadro clínico, entre eles: agulhamento seco, uso do spray de cloreto de etila ou fluormetano seguido por alongamento, injeçäo do ponto-gatilho com anestésicos ou soluçäo fisiológica salina também seguida por alongamento, compressäo isquêmica, técnicas de fricçäo profunda miofascial, TENS (estimulaçäo elétrica nervosa transcutânea), ultra-som, iontoforese, calor (seco e úmido), medicamentos analgésicos, antiinflamatórios ou relaxantes musculares, biofeedback. O objetivo desses tratamentos é a iliminaçäo do ponto gatilho, restauraçäo da amplitude de movimento e força muscular normais e sem dor. Além disso, é necessária uma educaçäo para o paciente prevenir e lidar com as recorrências e também bloquear os fatores precipitantes e/ou perpetuantes. Mas ainda há muitas divergências nos resultados de diferentes estudos, o que sugere uma análise crítica dos mesmos e uma maior preocupaçäo com as metodologias empregadas.

Substance P receptor (neurokinin-1)-expressing neurons in lamina I of the spinal cord encode for the intensity of noxious stimulation: a c-Fos study in rat.

The substance P receptor neurokinin-1 is expressed by a subset of neurons in the rat spinal cord. We have combined immunostaining for Fos, a marker of noxious peripheral stimulation, and neurokinin-1 to examine whether nociceptive signals from particular peripheral tissues (skin, muscle or knee joint) or activity generated by nerve injury or formalin-induced inflammation are preferentially modulated by substance P. Our results indicate that superficial and deep spinal neurokinin-1-positive neurons process nociceptive information in markedly different ways. In lamina I, the number of double-labelled neurons was positively correlated with the intensity of the stimulus (defined by the total Fos count) and was not directly related to any particular peripheral target. However, in the deeper layers of the spinal cord (V-X), there was no such correlation, and stimulation of joint nociceptors and formalin-induced inflammation produced the greatest proportion of Fos/neurokinin-1 co-localization, suggesting a particular role for substance P in the mediation of joint pain and inflammatory hyperalgesia. Thus, lamina I neurokinin-1 receptor-bearing neurons appear to be involved in intensity discriminative aspects of pain, whereas the deep neurokinin-1 cells are involved in spatial localization or the detection of particular nociceptive submodalities.

Tratamiento local y segmentario de los trastornos dolorosos / Local and segmentary treatment of pain disorders

Objetivos: el propósito de este estudio fue evaluar el efecto analgésico producido por la aplicación de dos técnicas electroterapéuticas en formas simultáneas. Material y Método: pacientes, treinta pacientes (trece hombres y diecisiete mujeres) asistieron en forma ambulatoria a tratamientos los cuales fueron seleccionados en forma aleatoria. Método: los treinta pacientes fueron sometidos a dos sesiones de tratamiento con Tens de alta frecuencia y baja intensidad y con corriente interferencial de baja frecuencia y elevada intensidad durante cuarenta minutos. Se utilizó la escala visual análoga para medir el grado de dolor. Las sesiones se realizaron en días sucesivos. Resultados: el efecto analgésico al término de la primera y segunda sesión fue estadísticamente significativo con un p<0,05. Discusión: los mecanismos analgésicos que pueden estar implicados con la utilización de Tens y corriente interferencial en forma simultánea son diversos. Para el Tens se mencionan mecanismos dinorfínicos, inhibición de la liberación de sustancia P, activación autonómica, y placebo, entre otros. Para la corriente interferencial se menciona: activación autonómica, mecanismos similares a los de electroacupuntura de baja frecuencia y placebo. Conclusión: los mecanismos analgésicos fueron de rápida instalación en pacientes con patologías variadas

Activation of CNS circuits producing a neurogenic cystitis: evidence for centrally induced peripheral inflammation.

We present a model of neurogenic cystitis induced by viral infection of specific neuronal circuits of the rat CNS. Retrograde infection by pseudorabies virus (PRV) of neuronal populations neighboring those that innervate the bladder consistently led to a localized immune response in the CNS and bladder inflammation. Infection of bladder circuits themselves or of circuits distant from these rarely produced cystitis. Absence of virus in bladder and urine ruled out an infectious cystitis. Total denervation of the bladder, selective C-fiber deafferentation, or bladder sympathectomy prevented cystitis without affecting the CNS disease, indicating a neurogenic component to the inflammation. The integrity of central bladder-related circuits is necessary for the appearance of bladder inflammation, because only CNS lesions affecting bladder circuits, i.e., bilateral dorsolateral or ventrolateral funiculectomy, as well as bilateral lesions of Barrington's nucleus/locus coeruleus area, prevented bladder inflammation. The close proximity in the CNS of noninfected visceral circuits to infected somatic neurons would thus permit a bystander effect, leading to activation of the sensory and autonomic circuits innervating the bladder and resulting in a neurogenic inflammation localized to the bladder. The present study indicates that CNS dysfunction can bring about a peripheral inflammation.