Biphasic modulation of visceral nociception by neurotensin in rat rostral ventromedial medulla.
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A potential role for neurotensin in the rostral ventromedial medulla (RVM) in modulation of visceral nociceptive transmission was examined in this study. Microinjection of neurotensin (3-3000 pmol) into the RVM of awake rats produced a dose-dependent inhibition of the visceromotor response (VMR) to noxious colorectal distension (CRD) that lasted 30 to 120 min. Additionally, intra-RVM injection of neurotensin (300 pmol) significantly reduced the slope of the stimulus-response function to graded CRD (20-80 mm Hg), whereas the greatest dose of neurotensin (3000 pmol) completely inhibited the VMR at all intensities of CRD. General motor function was unaffected after intra-RVM injection of neurotensin (3000 pmol). Intra-RVM injection of lesser doses of neurotensin (0.03-0.30 pmol) resulted an enhancement of the VMR to noxious CRD that had a short duration (18-30 min), and produced a leftward shift of the stimulus-response function to graded CRD without a change in the slope of the function. Additionally, intra-RVM injection of the neurotensin-receptor antagonist SR48692 (0.3-300 fmol) in naive animals produced dose-dependent inhibition of VMR to noxious CRD, whereas a lesser dose (0.03 fmol) enhanced the VMR. These data support a role for neurotensin in the RVM in biphasic modulation of visceral nociception. The results obtained with SR48692 suggest that endogenous neurotensin in the RVM modulates VMR to noxious CRD via a prominent interaction with neurotensin receptors that mediate facilitatory influences and a lesser interaction with neurotensin receptors that mediate masked inhibitory influences. (+info)
Laser ablations reveal functional relationships of segmental hindbrain neurons in zebrafish.
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Segmentation of the vertebrate brain is most obvious in the hindbrain, where successive segments contain repeated neuronal types. One such set of three repeated reticulospinal neurons--the Mauthner cell, MiD2cm, and MiD3cm--is thought to produce different forms of the escape response that fish use to avoid predators. We used laser ablations in larval zebrafish to test the hypothesis that these segmental hindbrain cells form a functional group. Killing all three cells eliminated short-latency, high-performance escape responses to both head- and tail-directed stimuli. Killing just the Mauthner cell affected escapes from tail-directed but not from head-directed stimuli. These results reveal the contributions of one set of reticulospinal neurons to behavior and support the idea that serially repeated hindbrain neurons form functional groups. (+info)
Role of metabotropic glutamate receptor subtype mGluR1 in brief nociception and central sensitization of primate STT cells.
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G-protein coupled metabotropic glutamate receptors (mGluRs) are important modulators of synaptic transmission in the mammalian CNS and have been implicated in various forms of neuroplasticity and nervous system disorders. Increasing evidence also suggests an involvement of mGluRs in nociception and pain behavior although the contribution of individual mGluR subtypes is not yet clear. Subtypes mGluR1 and mGluR5 are classified as group I mGluRs and share the ability to stimulate phosphoinositide hydrolysis and activate protein kinase C. The present study examined the role of group I mGluRs in nociceptive processing and capsaicin-induced central sensitization of primate spinothalamic tract (STT) cells in vivo. In 10 anesthetized male monkeys (Macaca fascicularis) extracellular recordings were made from 20 STT cells in the lumbar dorsal horn. Responses to brief (15 s) cutaneous stimuli of innocuous (BRUSH) and barely and substantially noxious (PRESS and PINCH, respectively) intensity were recorded before, during, and after the infusion of group I mGluR agonists and antagonists into the dorsal horn by microdialysis. Cumulative concentration-response relationships were obtained by applying different concentrations for at least 20 min each (at 5 microl/min). The actual concentrations reached in the tissue are 2-3 orders of magnitude lower than those in the microdialysis fibers (values in this paper refer to the latter). The group I antagonists were also applied at 10-25 min after capsaicin injection. S-DHPG, a group I agonist at both mGluR1 and mGluR5, potentiated the responses to innocuous and noxious stimuli (BRUSH > PRESS > PINCH) at low concentrations (10-100 microM; n = 5) but had inhibitory effects at higher concentrations (1-10 mM; n = 5). The mGluR5 agonist CHPG (1 microM-100 mM; n = 5) did not potentiate but inhibited all responses (10-100 mM; n = 5). AIDA (1 microM-100 mM), a mGluR1-selective antagonist, dose-dependently depressed the responses to PINCH and PRESS but not to BRUSH (n = 6). The group I (mGluR1 > mGluR5) antagonist CPCCOEt (1 microM-100 mM) had similar effects (n = 6). Intradermal injections of capsaicin sensitized the STT cells to cutaneous mechanical stimuli. The enhancement of the responses by capsaicin resembled the potentiation by the group I mGluR agonist S-DHPG (BRUSH > PRESS > PINCH). CPCCOEt (1 mM) reversed the capsaicin-induced sensitization when given as posttreatment (n = 5). After washout of CPCCOEt, the sensitization resumed. Similarly, AIDA (1 mM; n = 7) reversed the capsaicin-induced sensitization and also blocked the potentiation by S-DHPG (n = 5). These data suggest that the mGluR1 subtype is activated endogenously during brief high-intensity cutaneous stimuli (PRESS, PINCH) and is critically involved in capsaicin-induced central sensitization. (+info)
Movement-related cerebellar activation in the absence of sensory input.
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Movement-related cerebellar activation may be due to sensory or motor processing. Ordinarily, sensory and motor processing are obligatorily linked, but in patients who have severe pansensory neuropathies with normal muscle strength, motor activity occurs in isolation. In the present study, positron emission tomography and functional magnetic resonance imaging in such patients showed no cerebellar activation with passive movement, whereas there was prominent movement-related cerebellar activation despite absence of proprioceptive or visual input. The results indicate that motor processing occurs within the cerebellum and do not support the recently advanced view that the cerebellum is primarily a sensory organ. (+info)
Focal adhesion proteins FAK and paxillin increase in hypertrophied skeletal muscle.
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Components of signaling pathways for mechanotransduction during load-induced enlargement of skeletal muscle have not been completely defined. We hypothesized that loading of skeletal muscle would result in an adaptive increase in the expression of two focal adhesion complex (FAC)-related proteins, focal adhesion kinase (FAK) and paxillin, as well as increased FAK activity. FAK protein was immunolocalized to the sarcolemmal region of rooster anterior latissimus dorsi (ALD) myofibers in the middle of the ALD muscle. FAK (77 and 81%) and paxillin (206 and 202%) protein concentrations per unit of total protein in Western blots increased significantly after 1.5 and 7 days, but not after 13 days, of stretch-induced hypertrophy-hyperplasia of the ALD muscle. FAK autokinase activity in immunoprecipitates was increased after 1.5, 7, and 13 days in stretched ALD muscles. To determine whether increased FAK and paxillin protein concentrations are associated with hypertrophy and/or new fiber formation, two additional experiments were performed. First, during formation of primary chicken myotubes (a model of new fiber formation), FAK protein concentration (63%), FAK activity (157%), and paxillin protein concentration (97%) increased compared with myoblasts. Second, FAK (112% and 611%) and paxillin (87% and 431%) protein concentrations per unit of total protein in the soleus muscle increased at 1 and 8 days after surgical ablation of the synergistic gastrocnemius muscle (a model of hypertrophy without hyperplasia). Thus increases in components of the FAC occur in hypertrophying muscle of animals and in newly formed muscle fibers in culture. Furthermore, increased FAK activity suggests a possible convergence of signaling at the FAC in load-induced growth of skeletal muscle. (+info)
Stimulation of the paraventricular nucleus modulates the activity of gut-sensitive neurons in the vagal complex.
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There is good evidence that stimulation of the lateral hypothalamus excites neurons in the dorsal vagal complex (DVC), but the data regarding the role of the paraventricular nucleus (PVN) in vagal function are less clear. The purpose of this study was to clarify the effect of PVN stimulation on the activity of neurons in the DVC. We utilized extracellular and intracellular neuronal recordings with intracellular injections of a neuronal tracer to label individual, physiologically characterized neurons in the DVC of rats anesthetized with pentobarbital sodium. Most (80%) of the gut-sensitive dorsal motor nucleus of the vagus (DMNV) neurons characterized in this study exhibited a change in activity during electrical stimulation of the PVN. Stimulation of the PVN caused an increase in the spontaneous activity of 59% of the PVN-sensitive DMNV neurons, and the PVN was capable of modulating the response of a small subset of DMNV neurons to gastrointestinal stimuli. This study also demonstrated that the PVN was capable of influencing the activity of neurons in the nucleus of the solitary tract (NST). Electrical stimulation of the PVN decreased the basal activity of 66% of the NST cells that we characterized and altered the gastrointestinal response of a very small subset of NST neurons. It is likely that these interactions play a role in the modulation of a number of gut-related homeostatic processes. Increased or decreased activity in the descending pathway from the PVN to the DVC has the potential to alter ascending satiety signals, modulate vago-vagal reflexes and the cephalic phase of feeding, and affect the absorption of nutrients from the gastrointestinal tract. (+info)
Cerebral blood flow responses to somatosensory stimulation are unaffected by scopolamine in unanesthetized rat.
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Studies with positron-emission tomography have indicated that muscarinic acetylcholine receptors may be involved in the mechanism of enhancement of cerebral blood flow (CBF) by neuronal functional activation. We examined the effects of muscarinic receptor blockade by scopolamine on the local CBF responses to vibrissal stimulation in the whisker-to-barrel cortex sensory pathway in unanesthetized rats. Local CBF was measured by the quantitative autoradiographic [(14)C]iodoantipyrine method. Scopolamine (0.4 or 0.8 mg/kg) was injected i.v. 30 min before measurement of local CBF; control rats received equivalent volumes of physiological saline. Vibrissae on the left side of the face were stroked continuously throughout the 1-min period of measurement of CBF. Local CBF was determined bilaterally in four structures of the pathway, i.e., spinal and principal sensory trigeminal nuclei, ventral posteromedial thalamic nucleus, and barrel field of the sensory cortex, as well as in four representative structures unrelated to the pathway. The higher dose of scopolamine raised baseline CBF in the two trigeminal nuclei, but neither dose diminished the percentage of increases in local CBF because of vibrissal stimulation in any of the stations of the pathway. These results do not support involvement of muscarinic receptors in the mechanism of enhancement of local CBF by functional neuronal activation, at least not in the whisker-barrel cortex sensory pathway in the unanesthetized rat. (+info)
Sitting and low back pain: the positive effect of rotary dynamic stimuli during prolonged sitting.
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In this study the effect of dynamic stimuli on low back pain during prolonged sitting was investigated. The pain experience of two groups of 60 subjects with a specific low back pain was recorded. All subjects were investigated on pain behaviour by the Multidimensional Pain Inventory (MPI) and pain was measured on an open visual analogue scale (VAS). During sitting, one group received dynamic stimuli that were generated by alternating rotations in the horizontal plane of the seat of the chair, with back and arm rests in fixed position. Two different frequencies of rotation were applied in subgroups. The authors concluded that such stimuli, especially of the lower frequency, reduced pain in prolonged sitting. (+info)