Experimental colitis in mice and sensitization of converging visceral and somatic afferent pathways

2006 ◽  
Vol 290 (3) ◽  
pp. G451-G457 ◽  
Author(s):  
Kenneth Lamb ◽  
Fang Zhong ◽  
G. F. Gebhart ◽  
Klaus Bielefeldt

Chronic pain syndromes affecting different organs often coexist. We hypothesized that sensitization of one afferent pathway may affect converging input from other areas of the body. We induced colitis in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS); control animals were treated with equal volumes of vehicle (50% ethanol) only. Visceromotor responses to graded colorectal distension, cystometrograms, and response thresholds to mechanical and thermal stimulation of both hind paws were determined on days 7 and 14. Inflammation of colon and bladder was assessed with validated histological markers and scores. TNBS caused significant colitis on day 7 that resolved by day 14; there was no evidence of bladder inflammation. There was a significant hypersensitivity to colorectal distension on day 7, which returned to normal on day 14. This was associated with bladder overactivity, as demonstrated by early onset of micturition and more frequent micturition on day 7 after TNBS administration. Colitis also significantly altered responses to mechanical and thermal stimulation of both hind paws on day 7 but not day 14. We conclude that cross talk between afferent visceral and somatic pathways may contribute to the coexistence of pain syndromes.

1990 ◽  
Vol 63 (5) ◽  
pp. 1118-1127 ◽  
Author(s):  
L. Villanueva ◽  
K. D. Cliffer ◽  
L. S. Sorkin ◽  
D. Le Bars ◽  
W. D. Willis

1. Recordings were made in anesthetized monkeys from neurons in the medullary reticular formation (MRF) caudal to the obex. Responses of 19 MRF neurons to mechanical, thermal, and/or electrical stimulation were examined. MRF neurons exhibited convergence of nociceptive cutaneous inputs from widespread areas of the body and face. 2. MRF neurons exhibited low levels of background activity. Background activity increased after periods of intense cutaneous mechanical or thermal stimulation. Nearly all MRF neurons tested failed to respond to heterosensory stimuli (flashes, whistle sounds), and none responded to joint movements. 3. MRF neurons were excited by and encoded the intensity of noxious mechanical stimulation. Responses to stimuli on contralateral limbs were greater than those to stimuli on ipsilateral limbs. Responses were greater to stimuli on the forelimbs than to stimuli on the hindlimbs. 4. MRF neurons responded to noxious thermal stimulation (51 degrees C) of widespread areas of the body. Mean responses from stimulation at different locations were generally parallel to those for noxious mechanical stimulation. Responses increased with intensity of noxious thermal stimulation (45-50 degrees C). 5. MRF neurons responded with one or two peaks of activation to percutaneous electrical stimulation applied to the limbs, the face, or the tail. The differences in latency of responses to stimulating two locations along the tail suggested that activity was elicited by activation of peripheral fibers with a mean conduction velocity in the A delta range. Stimulation of the contralateral hindlimb elicited greater responses, with lower thresholds and shorter latencies, than did stimulation of the ipsilateral hindlimb. 6. Electrophysiological properties of monkey MRF neurons resembled those of neurons in the medullary subnucleus reticularis dorsalis (SRD) in the rat. Neurons in the caudal medullary reticular formation could play a role in processing nociceptive information. Convergence of nociceptive cutaneous input from widespread areas of the body suggests that MRF neurons may contribute to autonomic, affective, attentional, and/or sensory-motor processes related to pain.


1991 ◽  
Vol 260 (3) ◽  
pp. R486-R493 ◽  
Author(s):  
K. Kanosue ◽  
K. Niwa ◽  
P. D. Andrew ◽  
H. Yasuda ◽  
M. Yanase ◽  
...  

The present study explored the laterality of central nervous thermoregulatory control in anesthetized rats by measuring paw skin vasomotor activity and cold-induced shivering in hind leg muscles during unilateral preoptic area and anterior hypothalamus (POAH) warming and electrical stimulation or during unilateral thermal stimulation of abdominal skin. Unilateral POAH warming produced vasodilation on both sides of the body, but vasodilation on the ipsilateral side always either occurred at a lower threshold hypothalamic temperature or was stronger than on the contralateral side. In a cold environment (5 degrees C), shivering was suppressed simultaneously in both hind legs when one side of the POAH was warmed, and shivering reappeared simultaneously on both sides when POAH warming stopped. These results suggest that different thermoregulatory effectors are regulated in a different way by each side of the POAH. Unilateral thermal stimulation of the abdominal skin, on the other hand, affected vasomotor activity and shivering equally on both sides of the body, as previously reported for its influence on salivary secretion. Skin thermal signals from both sides of the body therefore seem to converge before they act on different thermoregulatory effector systems.


Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1081
Author(s):  
Nikoletta Almási ◽  
Szilvia Török ◽  
Zsuzsanna Valkusz ◽  
Máté Tajti ◽  
Ákos Csonka ◽  
...  

Inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gastrointestinal tract. Since the treatment of IBD is still an unresolved issue, we designed our study to investigate the effect of a novel therapeutic target, sigma-1 receptor (σ1R), considering its ability to activate antioxidant molecules. As a model, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used to induce colitis in Wistar–Harlan male rats. To test the beneficial effects of σ1R, animals were treated intracolonically (i.c.): (1) separately with an agonist (fluvoxamine (FLV)), (2) with an antagonist of the receptor (BD1063), or (3) as a co-treatment. Our results showed that FLV significantly decreased the severity of inflammation and increased the body weight of the animals. On the contrary, simultaneous treatment of FLV with BD1063 diminished the beneficial effects of FLV. Furthermore, FLV significantly enhanced the levels of glutathione (GSH) and peroxiredoxin 1 (PRDX1) and caused a significant reduction in 3-nitrotyrosine (3-NT) levels, the effects of which were abolished by co-treatment with BD1063. Taken together, our results suggest that the activation of σ1R in TNBS-induced colitis through FLV may be a promising therapeutic strategy, and its protective effect seems to involve the antioxidant pathway system.


1995 ◽  
Vol 198 (6) ◽  
pp. 1233-1242
Author(s):  
J R Groome ◽  
D K Vaughan ◽  
C M Lent

Thermal and chemical stimuli known to promote ingestive behaviours in the medicinal leech Hirudo medicinalis were tested for their physiological effects on Retzius neurones and for their biochemical effects on serotonin levels in the central nervous system, pharynx and body wall. Retzius neurones throughout the leech nerve cord receive excitatory synaptic input during thermal or chemical stimulation of the prostomial lip. These neurones respond to the rate of change of temperature as well as to absolute temperature at the lip. Exposure of the lip to sodium chloride excites Retzius neurones, whereas exposure to arginine has little effect. Thermal stimulation of the lip elicits a more rapid but less prolonged excitation of Retzius neurones than does chemical stimulation. Stimulation of the prostomial lip is associated with afferent activities in the cephalic nerves D1, D2 and V1-2. Thermal stimulation of the prostomial lip results in depletion of serotonin from midbody ganglia, whereas chemical stimulation has no effect. Conversely, chemical stimulation of the lip results in depletion of serotonin from the body wall, whereas thermal stimulation does not. Pharyngeal serotonin content is decreased with either modality. These data distinguish two important feeding-related sensory input pathways to central serotonergic effector neurones in Hirudo medicinalis.


1976 ◽  
Vol 39 (3) ◽  
pp. 564-581 ◽  
Author(s):  
B. W. Peterson ◽  
J. I. Franck ◽  
N. G. Daunton

1. In cats anesthetized with chloralose, responses of medial pontomedullary reticular neurons to stimulation of the body surface, vestibular nerves, superior colliculi, pericruciate cortices, cerebral peduncles, and spinal cord were studied at different stimulus rates. Raising the rate from 1/10 s to between 1/4 s and 2/s caused a significant decrement or increment in the response of most neurons tested. Response decrement typically began near the beginning of the higher frequency stimulus sequence and increased throughout the sequence. Response increment usually began somewhat later, rose to a peak, and then declined. Recovery from response decrement or increment usually occurred within 30-60 s at a 1/10 s stimulus rate.2. Measurements of response latency and of changes occurring in the initial and longer latency portions of responses indicated that all components of a response typically decreased or increased in parallel. Background spontaneous activity did not change during response decrements, but sometimes increased during response increment.3. Where changes could be detected, response decrement usually developed more rapidly when a sequence of repetitive stimulation was repeated.4. Response decrement was most pronounced at the highest stimulation rates and lowest stimulus intensities. Response increment was usually maximal at a stimulus rate of 1/s: at lower rates less increment occurred; at higher rates responses began to exhibit decrement.5. Response changes varied with the type of stimulus applied. Response decrements predominated when the body surface, vestibular nerves, or ipsilateral superior colliculus were stimulated. Approximately equal amounts of response increment and decrement were produced by repetitive stimulation of the cerebral peduncles and contralateral superior colliculus. Stimulation of the surface of the pericruciate cortex or of the spinal cord usually produced a long-lasting response increment.6. Generalization of response decrement and increment was observed in cases where trains of stimuli at a rate of 2/s applied to one point produced changes in the response to stimulation of another point which was tested once per 10 s and where single-shock stimulation of the first point was without effect on the test response. Generalization of response decrement occurred most often when two nearby points were stimulated. Generalization of response increment appeared to spread widely between distant cutaneous points and stimuli of different kinds.7. The response decrement and increment observed in medial pontomedullary reticular neurons displayed most of the parametric features of behavioral habituation and sensitization (8, 33) and therefore appear to represent neural analogs of these latter phenomena. The properties of response decrement suggest that it may occur to a large extent within afferent pathways leading to medial reticular neurons...


1989 ◽  
Vol 61 (2) ◽  
pp. 391-402 ◽  
Author(s):  
L. Villanueva ◽  
Z. Bing ◽  
D. Bouhassira ◽  
D. Le Bars

1. In anesthetized rats, recordings were made within the medullary subnucleus reticularis dorsalis (SRD) from neurons that exhibited convergence of nociceptive inputs from the entire body. Neurons with total nociceptive convergence (TNC) responded to suprathreshold percutaneous electrical stimuli (2-ms duration) with an early and a late peak due to activation of A delta- and C-fibers, respectively, no matter which part of the body was stimulated. Neurons with partial nociceptive convergence (PNC) responded to the same stimuli with an A delta-peak regardless of which part of the body was stimulated and with a C-peak of activation from some, mainly contralateral, parts of the body. The characteristics of the responses of these neurons to the application of graded intensities of electrical, thermal, and mechanical stimuli were analyzed. 2. All TNC neurons and 85% of PNC neurons responded to A delta- and C-fiber activation following percutaneous electrical stimulation of the contralateral hindpaw. With regard to A delta-fiber-evoked responses, a linear relationship between the logarithm of the applied current and the magnitude of the responses was found within the 0.25- to 6.0-mA and 0.5- to 24-mA ranges for TNC and PNC neurons, respectively; however, these curves were essentially similar. With regard to C-fiber-evoked responses, such a linear relationship was found within the 1.5- to 6.0-mA range for both types of SRD neurons, although the TNC neurons presented larger C-fiber-evoked responses than did the PNC neurons. 3. TNC and PNC neurons linearly increased their discharges during the application of noxious thermal stimuli to the contralateral hindpaw within the range 44-52 degrees C; the mean responses evoked by noxious heat from TNC neurons were of higher magnitude than those from PNC neurons. The majority of SRD neurons presented long-lasting afterdischarges, especially with the highest temperature employed (52 degrees C). 4. TNC neurons monotonically increased their discharges during graded mechanical or thermal stimulation of the tail. When mechanical stimuli were applied, a linear relationship was found between the logarithm of the strength of the mechanical stimulus and the neuronal discharges, in the 5.3- to 7.4-N/cm2 range. With thermal stimulation, TNC neurons linearly increased their discharges in the 44-52 degrees C range. When increasing amounts of the tail were immersed in a 50 degrees C waterbath, TNC neurons increased their discharges within a restricted range of tail surface areas (0.9-5.7 cm2); further increases in the stimulated surface size were not followed by increases in firing rate.(ABSTRACT TRUNCATED AT 400 WORDS)


2019 ◽  
Vol 1 (9) ◽  
pp. 38-46
Author(s):  
A. P. Babkin ◽  
A. A. Zuikova ◽  
O. N. Krasnorutskaya ◽  
Yu. A. Kotova ◽  
D. Yu. Bugrimov ◽  
...  

The widespread worldwide spread of acute respiratory diseases is an urgent problem in health care. Expressed polyetiology of respiratory diseases does not allow to limit the use of specific vaccine preparations and dictates the need to use to combat them a variety of non-specific means that stimulate the natural resistance of the human body. The main pharmacological action of sodium deoxyribonucleate is the stimulation of phagocytic activity of T-helpers and T-killers, increasing the functional activity of neutrophils and monocytes/ macrophages, providing regeneration and repair processes in the epithelial component of antiviral protection of the body. Based on the above, the study of the clinical efficacy of Derinat® in the form of spray in the treatment of acute respiratory viral infections is relevant.


2020 ◽  
pp. 15-18
Author(s):  
Inna R. Kilmetova ◽  
◽  
Igor A. Rodin ◽  
Nazira I. Khayrullina ◽  
Nikolay G. Fenchenko ◽  
...  

Summary. The disbalanced feeding and the uneven distribution of micro- and macroelements in the environment leads to a trace element, in particular hypomelanosis. To accelerate the growth and preservation of young farm animals include in the diet of various biological additives and drugs, which include selenium. For stimulation of weight gain in the livestock industry, as well as for the prevention and treatment of pathological processes in addition to micro - and macrouse amino acids, primarily methionine. The aim of this work was to study the influence of composition of DAFS-25+Polizon on morpho-biochemical parameters of blood and functional state of the liver in fattening bulls of black-motley breed in the conditions of the Republic of Bashkortostan. Experiments using were conducted on bull-calves of black-motley breed of the properties in the properties age from 6 to 15 months. The first experimental group during the experiment was additionally given the composition of DAFS-25+Polizon at a dose of 2 mg/kg, the animals of the control group received a standard diet. To assess the impact of the composition DAFS-25+Polizon on metabolism cattle studied morphological and biochemical indicators of blood and conducted histological examination of the liver. It is established that the use of the composition of DAFS-25+Polizon at a dose of 2 mg/kg increases the number of erythrocytes and hemoglobin in the experimental group and reduces the amount of white blood cells. The serum content of total protein, phosphorus and calcium increases in the group of experimental animals. Microscopic examination of the liver revealed no changes in the structure of the organ and hepatocytes in the experimental group, whereas in the control group hemodynamic disorders and dystrophic changes in liver cells were observed. Thus, the use of the composition DAFS-25+Polizon at a dose of 2 mg/kg of live weight in fattening bulls black-and-white breed contributes to the increase of redox processes in the body, stimulation of metabolism, prevent the development of liver disorders of cellular mechanisms of metabolism, optimizes the structure of the liver, which generally provides higher productivity.


1970 ◽  
Vol 63 (2) ◽  
pp. 325-337
Author(s):  
Carl-Johan Göthe

ABSTRACT The effect of three doses of prednisolone and ACTH respectively on the weight of the body, the lungs and the hilar lymph nodes was studied on rats killed one month after the intratracheal (i.t.) injection of 50 mg of fine-particulate quartz. The prednisolone was administered via the drinking water, and the ACTH was injected intraperitoneally during the period between the i.t. injection of quartz dust and the killing of the animals. Prednisolone causes the rats to become cachectic and reduces the weight of the hilar lymph nodes. It also retards the transport of quartz dust from the lungs via the lymphatics. All these effects increase with increasing doses of prednisolone. However, its effect on the lung weight is insignificant. ACTH does not affect the body weight, but retards the weight increase of the lungs and the hilar lymph nodes. These effects increase with increasing doses of ACTH, and seem to be connected with an ability of ACTH to promote the clearance of quartz dust from the lungs and hilar lymph nodes. The method used, however, does not make it possible to differentiate quantitatively between any ACTH effects on the bronchogenie and lymphatic lung-clearance mechanisms. Available data, however, indicate that the stimulation of the dust transport from the lungs and hilar lymph nodes is, at least to some extent, related to the lymphatic system.


2020 ◽  
Vol 21 (8) ◽  
pp. 744-750 ◽  
Author(s):  
Hongyang Li ◽  
JingyaWei ◽  
Fengtao Ma ◽  
Qiang Shan ◽  
Duo Gao ◽  
...  

In-depth studies have identified many hormones important for controlling mammary growth and maintaining lactation. One of these is melatonin, which is synthesized and secreted by the pineal gland to regulate circadian rhythms, improve antioxidant capacity, and enhance immunity. Prolactin is secreted by the pituitary gland and is associated with the growth and development of mammary glands as well as initiation and maintenance of lactation. The hypothalamus-pituitary system, the most important endocrine system in the body, regulates prolactin secretion mainly through dopamine released from tuberoinfundibular dopaminergic neurons. This review provides a reference for further study and describes the regulation of lactation and prolactin secretion by melatonin, primarily via the protection and stimulation of tuberoinfundibular dopaminergic neurons.


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