Inhibition and facilitation of different nocifensor reflexes by spatially remote noxious stimuli

1994 ◽  
Vol 72 (3) ◽  
pp. 1152-1160 ◽  
Author(s):  
M. M. Morgan ◽  
M. M. Heinricher ◽  
H. L. Fields
Keyword(s):  
Conditioning Stimulus ◽  
Hot Water ◽  
Noxious Stimulus ◽  
Tail Flick ◽  
Withdrawal Reflex ◽  
Dorsal Horns ◽  
Electrophysiological Studies ◽  
Noxious Stimuli ◽  
Evoked Activity ◽  
Lumbar Spinal

1. Noxious stimuli have been shown to produce a diffuse inhibition of nociresponsive neurons in the spinal and trigeminal dorsal horns. The present study sought to extend these electrophysiological studies of diffuse noxious inhibitory controls (DNIC) by determining the effect of a spatially remote noxious stimulus on behavioral measures of nociception. Changes in latency for hindpaw withdrawal and tail flick reflexes were measured in lightly halothane-anesthetized or awake, spinally transected rats before, during, and after application of a spatially remote noxious stimulus. 2. Surprisingly, in no case did application of a spatially remote noxious stimulus inhibit the hindpaw withdrawal reflex. The latency for this reflex was either reduced or did not change when the tail or contralateral hindpaw was placed in hot water (50 degrees C) or when a noxious pinch was applied to the ear. In contrast, the latency for the tail flick reflex was consistently increased when the hindpaw was placed in hot water. Both the hindpaw reflex facilitation and the tail flick reflex inhibition produced by a noxious conditioning stimulus were attenuated in spinally transected rats indicating supraspinal modulation of both reflexes. 3. In addition, and consistent with the work of others, placing the tail in hot water reduced the evoked activity of convergent neurons in both the trigeminal and lumbar spinal dorsal horns. Thus inhibition of the activity of nociresponsive neurons in the dorsal horn is consistent with inhibition of the tail flick reflex, but not with facilitation of the hindpaw withdrawal reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Pronounced changes in the activity of nociceptive modulatory neurons in the rostral ventromedial medulla in response to prolonged thermal noxious stimuli

1994 ◽  
Vol 72 (3) ◽  
pp. 1161-1170 ◽  
Author(s):  
M. M. Morgan ◽  
H. L. Fields
Keyword(s):  
Cell Activity ◽  
Conditioning Stimulus ◽  
Hot Water ◽  
Noxious Stimulus ◽  
Rostral Ventromedial Medulla ◽  
Tail Flick ◽  
Noxious Heat ◽  
Ventromedial Medulla ◽  
On And Off Cells ◽  
Noxious Stimuli

1. Brain regions that inhibit nociception can be activated by various environmental stimuli, including prolonged noxious stimuli. The present study tested the effect of such a prolonged noxious stimulus on the activity of nociceptive modulatory neurons in the rostral ventromedial medulla (RVM). These neurons, called ON- and OFF-cells because of their respective burst and pause in activity associated with nocifensor reflexes, have been shown to facilitate and inhibit nociception, respectively. 2. Single-unit activity of ON- and OFF-cells was assessed in lightly halothane- or barbiturate-anesthetized rats exposed to prolonged noxious heat (50 degrees C water). This prolonged noxious stimulus caused an increase in ON-cell and a decrease in OFF-cell activity regardless of anesthetic (halothane or barbiturate) or stimulus location (hindpaw or tail). 3. Surprisingly, and despite the consistent changes in RVM cell activity, the prolonged noxious stimulus caused different effects depending on the reflex used to assess nociception. The hindpaw withdrawal reflex was facilitated when the tail was immersed in hot water, whereas the tail flick reflex was inhibited when the hindpaw was immersed in hot water (see preceding manuscript). Lidocaine inactivation of the RVM shortened the latency for both reflexes but had no effect on tail flick inhibition produced by the noxious conditioning stimulus. In contrast, lidocaine inactivation of the RVM completely reversed the hindpaw reflex facilitation produced by tail heat, indicating the involvement of RVM ON-cells in facilitation of this reflex. 4. These data demonstrate that RVM neurons respond in a consistent manner to noxious stimuli whether applied for a brief or prolonged time: ON-cell activity increases and OFF-cell activity decreases. Moreover, the activation of RVM ON-cells produced by a noxious stimulus is sufficient to enhance some nocifensor reflexes, whereas neural structures other than the RVM appear to mediate the antinociceptive effects produced by a prolonged noxious stimulus.

Spinal pathways mediating tonic, coeruleospinal, and raphe-spinal descending inhibition in the rat

1987 ◽  
Vol 58 (1) ◽  
pp. 138-159 ◽  
Author(s):  
S. L. Jones ◽  
G. F. Gebhart
Keyword(s):  
Spontaneous Activity ◽  
Dorsal Horn ◽  
Unit Activity ◽  
Tail Flick ◽  
Descending Inhibition ◽  
Nociceptive Transmission ◽  
Dorsal Horn Neurons ◽  
C Fibers ◽  
Electrophysiological Studies ◽  
Evoked Activity

1. The contribution of midline medullary bulbospinal neurons to descending inhibition from the locus coeruleus (LC) and the funicular trajectories of coeruleo- and raphe-spinal fibers mediating inhibition of spinal nociceptive transmission were examined in different experiments. Extracellular recordings of lumbar dorsal horn neurons were made in deeply pentobarbital-anesthetized, paralyzed rats. All units studied responded to electrical stimulation of the ipsilateral tibial nerve at intensities supramaximal to activate A-alpha-delta- and C-fibers and to mechanical and heat (50 degrees C) stimuli of the glabrous skin of the ipsilateral hind foot. Parallel studies were done in lightly pentobarbital-anesthetized rats utilizing the nociceptive tail-flick (TF) reflex. 2. To examine the contribution of bulbospinal neurons in the nucleus raphe magnus (NRM) to descending coeruleospinal inhibition, lidocaine microinjections were made into the NRM to produce a time-limited, reversible block. Lidocaine microinjections into the NRM effectively blocked NRM stimulation-produced inhibition of the TF reflex (prelidocaine stimulation thresholds were increased two to three times), but did not affect stimulation-produced inhibition from the LC. 3. In parallel electrophysiological studies, stimulation in the NRM inhibited heat-evoked dorsal horn unit activity to 31% of control, whereas stimulation in the LC/SC inhibited heat-evoked activity of the same units to 30% of control. Following NRM lidocaine microinjections, stimulation at the same intensity in the NRM no longer inhibited heat-evoked activity (93% of control), confirming the efficacy of the lidocaine block. LC stimulation-produced inhibition, however, was not affected by blockage of the NRM; heat-evoked unit activity was inhibited by LC stimulation to 39% of control. 4. The effects of ipsilateral and bilateral ventrolateral funiculus (VLF) lidocaine microinjections on spontaneous and heat-evoked unit activity were examined in other experiments. Spontaneous activity increased following ipsilateral VLF lidocaine microinjections for 13/18 units; decreases and no change in spontaneous activity were observed for three and two units, respectively. Heat-evoked unit activity was increased significantly following ipsilateral VLF lidocaine microinjections.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-inflammatory and analgesic effects of methanol extract of red cultivar Allium cepa bulbs in rats and mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Adeoye Joshua Oyewusi ◽  
Olayinka Ayotunde Oridupa ◽  
Adebowale Bernard Saba ◽  
Ibironke Kofoworola Oyewusi ◽  
Jonny Olufemi Olukunle
Keyword(s):  
Allium Cepa ◽  
Methanol Extract ◽  
Biological Activities ◽  
Hot Water ◽  
Control Group ◽  
Tail Flick ◽  
Control Groups ◽  
Inflammatory Models ◽  
Paw Oedema ◽  
Anti Inflammatory

Abstract Objectives Several cultivars of Allium cepa L. have been studied for anti-inflammatory and analgesic activities but there is inadequate information on such biological activities of the concentrated extracts of the Nigerian grown red cultivar A. cepa bulb. Methods The anti-inflammatory models used in this study were Carrageenan-induced paw oedema and formalin-induced paw lick in rats, while acetic acid-induced abdominal writhing, hot plate reaction, hot water tail flick tests in mice were the analgesic models. Results At 30 min post-induction (pi), the inhibition of paw oedema (62.50%) by 200 mg/kg of methanol extract of red cultivar A. cepa bulb (MERCACB) was significantly (p<0.001) higher than that of indomethacin (15.63%) at 10 mg/kg. The paw oedema inhibition at 60 min pi by MERCACB (76.92%) was significantly higher than that of indomethacin (41.03%). At the early phase of formalin paw-lick test, the pain reaction time (PRT) of rat treated with MERCACB (400 mg/kg) was significantly lower than that of indomethacin and the control groups. The hotplate test revealed that PRT of mice treated with 800 mg/kg of MERCACB were significantly (p<0.01) longer in comparism to indomethacin and control groups. The PRT of mice subjected to thermal pain due to hot water and treated with 800 mg/kg of MERCACB was significantly (p<0.05) longer than that of the control group. Conclusions These findings indicate that MERCACB possesses potent anti-inflammatory and analgesic properties which confirm the traditional use of the plant for the treatment of inflammatory diseases and may be useful as a future therapeutic agent.

Halothane Suppression of Spinal Sensory Neuronal Responses to Noxious Peripheral Stimuli Is Mediated, in Part, by Both GABAAand Glycine Receptor Systems

2002 ◽  
Vol 97 (2) ◽  
pp. 412-417 ◽  
Author(s):  
Masanori Yamauchi ◽  
Hiroshi Sekiyama ◽  
Steven G. Shimada ◽  
J. G. Collins
Keyword(s):  
Dynamic Range ◽  
Glycine Receptor ◽  
Gamma Aminobutyric Acid ◽  
Neuronal Responses ◽  
General Anesthetic ◽  
Gaba A ◽  
Low Threshold ◽  
Noxious Stimuli ◽  
Evoked Activity ◽  
Wdr Neurons

Background A major effect of general anesthesia is lack of response in the presence of a noxious stimulus. Anesthetic depression of spinal sensory neuronal responses to noxious stimuli is likely to contribute to that essential general anesthetic action. The authors tested the hypothesis that gamma-aminobutyric acid receptor type A (GABA(A)) and strychnine-sensitive glycine receptor systems mediate halothane depression of spinal sensory neuronal responses to noxious stimuli. Methods Extracellular activity of single spinal dorsal horn wide dynamic range (WDR) neurons was recorded in decerebrate, spinal cord transected rats. Neuronal responses to noxious (thermal and mechanical) and nonnoxious stimuli were examined in the drug-free state. Subsequently, cumulative doses (0.1-2.0 mg/kg) of bicuculline (GABA(A) antagonist) or strychnine (glycine antagonist) were administered intravenously in the absence or presence of 1 minimum alveolar concentration (MAC) of halothane. Results Halothane, 1.1%, depressed the response of WDR neurons to both forms of noxious stimuli. Antagonists, by themselves, had no effect on noxiously evoked activity. However, bicuculline and strychnine (maximum cumulative dose, 2.0 mg/kg) partially but significantly reversed the halothane depression of noxiously evoked activity. Similar results were seen with most, but not all, forms of nonnoxiously evoked activity. In the absence of halothane, strychnine significantly increased neuronal responses to low threshold receptive field brushing. Conclusion Halothane depression of spinal WDR neuronal responses to noxious and most nonnoxious stimuli is mediated, in part, by GABA(A) and strychnine-sensitive glycine systems. A spinal source of glycine tonically inhibits some forms of low threshold input to WDR neurons.

scholarly journals NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-κB/COX-2/PG pathway

2020 ◽  
Author(s):  
tang biao ◽  
Liu Dan ◽  
Chen Lingyu ◽  
liu yu
Keyword(s):  
Nlrp3 Inflammasome ◽  
Hot Water ◽  
Prostaglandin E ◽  
Tail Flick ◽  
Inflammasome Activation ◽  
Primary Dysmenorrhea ◽  
Tail Flick Test ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation ◽  
Cox 2

Abstract Background: Primary dysmenorrhea (PD) constitutes a common gynecological disease among young women. The NLRP3 inflammasome may be activated and expressed in PD, but the mechanistic link between NLRP3 inflammasome activation and PD is still unclear.Methods: To investigate the potential role of NLRP3 inflammasome activation in the pathogenesis of PD, thirty female Kunming mice without pregnancy were used for experiments. The PD mouse model was constructed by 11 days of successive co-treatment with estradiol and oxytocin. MCC950, a potent and specific small-molecule inhibitor of the NLRP3 inflammasome, was used to treat PD mice. The disease level was assessed by the writhing response and hot water tail-flick test. The levels of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2α) in the uterine tissues of mice were detected by ELISA. The expression levels of protein and cytokines, including NLRP3, cysteine aspartic acid-specific protease 1 (caspase-1), interleukin (IL)-1β, IL-18, nuclear factor kappa B (NF-κB) p65, phospho-NF-κB p65, and cyclooxygenase-2 (COX-2) were revealed by western blot analysis.Results: MCC950 greatly ameliorated the writhing response induced by the combination of oxytocin and estradiol, with an increasing length of tail-flick latency. MCC950 also significantly decreased the levels of PGF2α and PGE2, and the expressions of NLRP3, caspase-1, IL-1β, IL-18, phospho-NF-κB p65, NF-κB p65, and COX-2 in the uterus.Conclusions: MCC950 markedly alleviated the pain and pathological damage in PD mice by inhibiting NLRP3 activation. The underlying mechanism may be related to hypoactive uterine inflammation via suppression of NLRP3 activation and the NF-κB/COX-2/PG pathway in uteruses of PD mice.

scholarly journals Potensi Infusa Kemiri (Aleurites moluccana) sebagai Analgesik dan Stimulator Stamina

2021 ◽  
Vol 9 (1) ◽  
pp. 14-20
Author(s):  
Fajar Anaba ◽  
Andriyanto ◽  
Ni Luh Putu Ika Mayasari
Keyword(s):  
Analysis Of Variance ◽  
Water Immersion ◽  
Hot Water ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Aleurites Moluccana ◽  
Hot Water Immersion

Kesehatan merupakan hal penting untuk menjalankan aktivitas sehari-hari. Penurunan kesehatan dan daya tahan tubuh mengakibatkan timbul rasa nyeri serta mudah terserang penyakit. Pengobatan herbal digunakan sebagai pengobatan alternatif yang lebih aman dan terjangkau dibandingkan pengobatan nonherbal dari bahan-bahan kimia. Kemiri merupakan salah satu tanaman herbal yang memiliki banyak khasiat dan sering digunakan sebagai pengobatan oleh masyarakat. Penelitian ini bertujuan mempelajari efektivitas infusa kemiri sebagai analgesik dan stimulator stamina dalam berbagai dosis pada mencit. Uji efektivitas analgesik ditinjau menggunakan metode hot water immersion tail-flick test dan uji efektivitas stamina menggunakan metode natatory enhausen. Penelitian ini menggunakan 20 ekor mencit jantan yang dikelompokkan menjadi kelompok kontrol dan kelompok perlakuan yang diberi infusa kemiri dengan dosis 1, 2, dan 4 g/kg BB. Setiap kelompok terdiri atas 5 ekor. Data dianalisis menggunakan analysis of variance (ANOVA) kemudian dilanjutkan dengan uji Tukey. Hasil penelitian didapatkan dosis efektif pada uji analgesik adalah 4 g/kg BB dengan waktu respons nyeri ekor terlama yaitu 7.840±0.477 detik dan pada uji stamina adalah 1 g/kg BB yang ditunjukkan dengan durasi berenang terlama yaitu 145.00±20.65 detik. Kemiri memiliki efektivitas terhadap analgesik dan stimulator stamina.

Synaptic transmission through cat lumbar ascending sensory pathways is suppressed during active sleep

1993 ◽  
Vol 70 (4) ◽  
pp. 1708-1712 ◽  
Author(s):  
P. J. Soja ◽  
J. I. Oka ◽  
M. Fragoso
Keyword(s):  
Sciatic Nerve ◽  
Field Potential ◽  
Behavioral State ◽  
Gamma Aminobutyric Acid ◽  
Active Sleep ◽  
Long Duration ◽  
Evoked Activity ◽  
Few Data ◽  
Sciatic Nerve Stimulation ◽  
Lumbar Spinal

1. Few data are available that describe the evoked activity of spinal cord sensory tract neurons as a function of behavioral state. Accordingly, experiments were performed in which ascending volleys were recorded extracellularly within the spinoreticular (SRT), spinothalamic (STT), and spinomesencephalic (SMT) tracts located in the ventrolateral reticular formation in response to low-intensity electrical stimulation of the contralateral sciatic nerve in the chronic unanesthetized, behaving cat during naturally occurring episodes of wakefulness, quite sleep, and active sleep. 2. During episodes of wakefulness and quite sleep sciatic nerve stimulation produced a low-amplitude and long-duration orthodromic field potential that did not differ in amplitude or waveform. However, during the corresponding episode of active sleep, the sciatic nerve-induced orthodromic field potential was markedly suppressed or abolished. 3. The effects of sustained microiontophoretic applications of inhibitory amino acid agonists, glycine, or gamma-aminobutyric acid during wakefulness or quite sleep markedly suppressed the antidromic field potential recorded from nearby VII motoneurons but did not alter the sciatic nerve-evoked orthodromic field potential, indicating that the sciatic response was recorded from ascending axons of passage emanating from lumbar spinal neurons. We suggest that lumbar neurons comprising the SRT, STT, and SMT tracts are subjected to a descending suppressor drive that is activated specifically during the behavioral state of active sleep.

Selective inhibition of glucose-sensitive neurons in rat lateral hypothalamus by noxious stimuli and morphine

1985 ◽  
Vol 53 (1) ◽  
pp. 17-31 ◽  
Author(s):  
S. K. Sikdar ◽  
Y. Oomura
Keyword(s):  
Selective Inhibition ◽  
Hot Water ◽  
Noxious Stimulation ◽  
Exact Probability ◽  
Endogenous Opiates ◽  
Hypothalamic Area ◽  
Neurophysiological Mechanisms ◽  
Glucose Sensitivity ◽  
Noxious Stimuli ◽  
Feeding Control

On the basis of their responsiveness to electrophoretically applied glucose, neurons in the lateral hypothalamic area (LHA) have been characterized as either glucose sensitive or glucose nonsensitive. Glucose-sensitive neurons are important in feeding control (4, 36-38, 44, 54). The aim of this study was to increase understanding of the neurophysiological mechanisms involved in the disturbance of feeding by pain. Radiant heating of the scrotum, strong tail pinch, and immersion of the tail in hot water were used as noxious stimuli. In order to correlate the responses of LHA neurons to noxious inputs with possible local release of endogenous opiates, effects of electrophoretically applied morphine and naloxone were also tested. The effects of glucose, morphine, and noxious stimulation were studied in a total of 165 neurons recorded from 75 adult male urethane-chloralose-anesthetized rats. Of 52 neurons determined to be glucose sensitive, 36 (69%) were inhibited by both noxious stimulation and morphine. A majority of the glucose-nonsensitive neurons did not respond to either morphine or noxious stimulation (87/113, 74%). The relation of glucose sensitivity to inhibition by pain and/or morphine was statistically significant (Fisher's exact probability test, P less than 0.01). Naloxone attenuated the inhibitory effects of both pain and morphine, thus suggesting mediation of both by the same neuronal mechanism. From this evidence we conclude that LHA glucose-sensitive neurons are involved in the suppression of feeding by noxious stimulation.

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