Modulation of Noxious and Non-Noxious Spinal Mechanical Transmission From the Rostral Medial Medulla in the Rat

2002 ◽  
Vol 88 (6) ◽  
pp. 2928-2941 ◽  
Author(s):  
M. Zhuo ◽  
G. F. Gebhart
Keyword(s):  
Electrical Stimulation ◽  
Mechanical Stimulation ◽  
Spinal Neuron ◽  
Noxious Stimulation ◽  
Mechanical Transmission ◽  
Inhibitory Effects ◽  
Stimulus Response ◽  
Hind Foot ◽  
Descending Influences ◽  
Noxious Mechanical Stimulation

Modulatory influences on spinal mechanical transmission from the rostral medial medulla (RMM) were studied. Noxious stimulation, produced by von Frey-like monofilaments, and non-noxious stimulation, produced by a soft brush, was applied to the glabrous skin of the hind foot. At 28 sties in RMM, electrical stimulation facilitated responses to noxious mechanical stimulation at low intensities (5–25 μA) and inhibited responses of the same neurons at greater intensities (50–100 μA) of stimulation. At 24 and 9 other sites in RMM, stimulation at all intensities only inhibited or only facilitated, respectively, responses to noxious mechanical stimulation of the hind foot. Stimulus-response functions to mechanical stimulation were shifted leftward by low intensities and decreased by high intensities of stimulation. Inhibitory influences were found to descend in the dorsolateral funiculi; facilitatory effects were contained in the ventral spinal cord. Descending modulation of non-noxious brush stimulation revealed biphasic facilitatory-inhibitory effects (9 sites in RMM), only inhibitory effects (14 sites) and only facilitatory effects (8 sites). The effects of electrical stimulation were replicated by intra-RMM administration of glutamate; a low concentration (0.25 nmol) facilitated and a greater concentration (2.5 nmol) inhibited spinal mechanical transmission, providing evidence that cells in RMM are sufficient to engage descending influences. Descending modulatory effects were specific for the site of stimulation, not for the spinal neuron, because modulation of the same neuron was different from different sites in RMM. These results show that spinal mechanical transmission, both noxious and non-noxious, is subject to descending influences, including facilitatory influences that may contribute to exaggerated responses to peripheral stimuli in some chronic pain states.

Characterization of descending facilitation and inhibition of spinal nociceptive transmission from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat

1992 ◽  
Vol 67 (6) ◽  
pp. 1599-1614 ◽  
Author(s):  
M. Zhuo ◽  
G. F. Gebhart
Keyword(s):  
Electrical Stimulation ◽  
Receptive Fields ◽  
Rapid Onset ◽  
Mechanical Stimuli ◽  
Nociceptive Transmission ◽  
Stimulus Response ◽  
Descending Facilitation ◽  
Spinal Segments ◽  
Hind Foot ◽  
Descending Influences

1. Descending influences produced by focal electrical stimulation in the nuclei reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha) on spinal nociceptive transmission and the dorsoventral region of spinal white matter mediating stimulation-produced modulation were examined in pentobarbital sodium-anesthetized, paralyzed rats. Spinal units studied responded to mechanical stimuli and noxious heating (50 degrees C) of cutaneous receptive fields confined to the glabrous skin of the ipsilateral hind foot. Recording sites were located in laminae I-VI of the L3-L5 spinal segments. 2. Electrical stimulation in the NGC or NGC alpha produced both facilitation and inhibition of responses of spinal units to noxious heating of the skin. At 33 of 57 stimulation sites in the NGC and NGC alpha, electrical stimulation produced biphasic effects, facilitating responses at lesser intensities (5-25 microA) and inhibiting responses at greater intensities (50-100 microA). At 21 other sites in the NGC and NGC alpha, electrical stimulation (5-100 microA) only inhibited, and at 3 sites stimulation (5-100 microA) only facilitated responses of spinal units to noxious heating of the skin. 3. Electrical stimulation in the NGC or NGC alpha contralateral to the spinal recording site produced the same magnitude of facilitation/inhibition or inhibition of spinal nociceptive transmission as did stimulation in the ipsilateral NGC and NGC alpha. 4. The latencies to descending facilitation and inhibition of spinal nociceptive transmission from the NGC and NGC alpha were estimated by a cumulative sum technique to be 232 and 80 ms, respectively. 5. Responses of spinal units to graded heating (42-50 degrees C) of the skin exhibited positively accelerating stimulus-response functions (SRF) throughout the temperature range tested. Electrical stimulation at lesser, "facilitating" intensities produced a parallel, leftward shift of the SRF, whereas stimulation at greater, "inhibitory" intensities significantly decreased the slope of the SRF without affecting the threshold for response. 6. To determine whether activation of cell bodies in the NGC or NGC alpha were capable of replicating the effects of electrical stimulation, L-glutamate was microinjected into sites where electrical stimulation facilitated at lesser and inhibited at greater intensities the responses of spinal units to 50 degrees C heating of the skin. L-Glutamate (5 nmol) produced a rapid onset, short-lasting and reproducible facilitation of nociceptive transmission; glutamate microinjection into the same site at a greater dosage (50 nmol) inhibited responses of the same spinal units.(ABSTRACT TRUNCATED AT 400 WORDS)

Convergence of heterotopic nociceptive information onto neurons of caudal medullary reticular formation in monkey (Macaca fascicularis)

1990 ◽  
Vol 63 (5) ◽  
pp. 1118-1127 ◽  
Author(s):  
L. Villanueva ◽  
K. D. Cliffer ◽  
L. S. Sorkin ◽  
D. Le Bars ◽  
W. D. Willis
Keyword(s):  
Electrical Stimulation ◽  
Reticular Formation ◽  
Mechanical Stimulation ◽  
Background Activity ◽  
The Body ◽  
Thermal Stimulation ◽  
Medullary Reticular Formation ◽  
Nociceptive Information ◽  
Noxious Mechanical Stimulation ◽  
Stimulation Of

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.

Responses of neurons in VPL and VPL-VL region of the cat to algesic stimulation of muscle and tendon

1983 ◽  
Vol 49 (3) ◽  
pp. 649-661 ◽  
Author(s):  
K. D. Kniffki ◽  
K. Mizumura
Keyword(s):  
Electrical Stimulation ◽  
Mechanical Stimulation ◽  
Receptive Fields ◽  
Transitional Zone ◽  
The Other ◽  
Group Iii ◽  
Group I ◽  
Nociceptive Information ◽  
Noxious Mechanical Stimulation ◽  
Stimulation Of

1. The responses evoked by electrical stimulation of cutaneous and muscle nerves, by noxious and innocuous mechanical stimulation of muscle, tendon, and cutaneous tissues, and by intra-arterial (ia) injection of algesic substances (potassium, bradykinin) into arteries supplying the gastrocnemius-soleus muscle (GS) were studied in single neurons located in the ventroposterolateral nucleus (VPL) and in the transitional zone between VPL and the ventrolateral nucleus (VL) of cats lightly anesthetized with thiopenthal. Such chemical stimulation of the muscles has been shown to activate muscular groups III and IV axons specifically (43, 44) and presumably is nociceptive in character (14, 17, 31). 2. One hundred eight neurons were tested. Eighty-three of the units responded only to various types of cutaneous stimulation of the hindlimb. The other 25 responded to algesic stimulation of muscle and/or tendon. Of these latter 25, 7 had no apparent cutaneous receptive field although 4 of them responded to electrical stimulation of the common peroneal and/or sural nerve. Thus, only three neurons responded exclusively to algesic chemical and noxious mechanical stimulation of the muscle. Of the other 18 neurons, 14 had cutaneous receptive fields restricted to the hindlimb and often responded to non-noxious repetitive light stroking and to noxious pinching with a high-frequency discharge. Four cells (two of which had cutaneous input only from low-threshold mechanoreceptors) had complex and large receptive fields extending to more than one limb. 3. Potassium was a more potent muscle receptor stimulant than bradykinin, the latter only weakly exciting 3 neurons of 24 tested with both substances. The responses to potassium were rapid (approximately 4.0 s in latency) and tended to be greater (have higher response rates) for the units that responded to cutaneous as well as muscle/tendon stimulation. 4. Most neurons that responded to noxious deep stimulation had a threshold for the GS nerve volley in the group III fiber range. The few neurons with thresholds slightly below the group III range did not respond to activation of group I or II muscle spindle afferents by intra-arterial application of succinylcholine or by stretching the muscle. 5. Neurons with responses to any of the muscle, tendon, or cutaneous nociceptive stimuli were located at the ventral and dorsal periphery of VPL and in the VPL-VL transitional zone. 6. These results strongly suggest that there exist regions within the lateral diencephalon of cats that are capable of processing nociceptive information and that these regions are located at the periphery of VPL.

Processing of Nociceptive Mechanical and Thermal Information in Central Amygdala Neurons With Knee-Joint Input

2002 ◽  
Vol 87 (1) ◽  
pp. 103-112 ◽  
Author(s):  
Volker Neugebauer ◽  
Weidong Li
Keyword(s):  
Knee Joint ◽  
Mechanical Stimulation ◽  
Receptive Fields ◽  
Central Nucleus ◽  
Response Functions ◽  
Central Amygdala ◽  
Deep Tissue ◽  
Stimulus Response ◽  
Noxious Mechanical Stimulation ◽  
Stimulation Of

Pain has a strong emotional dimension, and the amygdala plays a key role in emotionality. The processing of nociceptive mechanical and thermal information was studied in individual neurons of the central nucleus of the amygdala, the target of the spino-parabrachio-amygdaloid pain pathway and a major output nucleus of the amygdala. This study is the first to characterize nociceptive amygdala neurons with input from deep tissue, particularly the knee joint. In 46 anesthetized rats, extracellular single-unit recordings were made from 119 central amygdala neurons that were activated orthodromically by electrical stimulation in the lateral pontine parabrachial area and were tested for receptive fields in the knee joints. Responses to brief mechanical stimulation of joints, muscles, and skin and to cutaneous thermal stimuli were recorded. Receptive-field sizes and thresholds were mapped and stimulus-response functions constructed. Neurons in the central nucleus of the amygdala with excitatory input from the knee joint ( n = 62) typically had large symmetrical receptive fields in both hindlimbs or in all four extremities and responded exclusively or preferentially to noxious mechanical stimulation of deep tissue ( n = 58). Noxious mechanical stimulation of the skin excited 30 of these neurons; noxious heat activated 21 neurons. Stimulus-response data were best fitted by a sigmoid nonlinear regression model rather than by a monotonically increasing linear function. Another 15 neurons were inhibited by noxious mechanical stimulation of the knee joint and other deep tissue. Fifteen neurons had no receptive field in the knee but responded to noxious stimulation of other body areas; 27 nonresponsive neurons were not activated by natural somesthetic stimulation. Our data suggest that excitation is the predominant effect of brief painful stimulation of somatic tissue on the population of central amygdala neurons with knee joint input. Their large symmetrical receptive fields and sigmoid rather than monotonically increasing linear stimulus-response functions suggest a role of nociceptive central amygdala neurons in other than sensory-discriminative aspects of pain.

Responses of Spinothalamic Lamina I Neurons to Maintained Noxious Mechanical Stimulation in the Cat

2002 ◽  
Vol 87 (4) ◽  
pp. 1889-1901 ◽  
Author(s):  
D. Andrew ◽  
A. D. Craig
Keyword(s):  
Mechanical Stimulation ◽  
Mechanical Stimuli ◽  
Spinothalamic Tract ◽  
Stimulus Response ◽  
Lamina I ◽  
C Fiber ◽  
Response Profiles ◽  
Noxious Mechanical Stimulation ◽  
First Pain ◽  
Thermal Stimuli

Noxious mechanical stimuli that are maintained for minutes produce a continuous sensation of pain in humans that augments during the stimulus. It has recently been shown with systematic force-controlled stimuli that, while all mechanically responsive nociceptors adapt to these stimuli, the basis for such pain can be ascribed to A-fiber rather than C-fiber nociceptors, based on distinctions in their respective response profiles and stimulus-response functions. The present experiments investigated whether similar distinctions could be made in subsets of nociceptive lamina I spinothalamic tract (STT) neurons using similar maintained stimuli. Twenty-eight lamina I STT neurons in the lumbosacral dorsal horn of barbiturate-anesthetized cats were tested with noxious mechanical stimuli applied with a probe of 0.1 mm2 contact area at forces of 25, 50, and 100 g for 2 min. The neurons were classified as nociceptive-specific (NS, n = 14) or polymodal nociceptive (HPC, n = 14) based on their responses to quantitative thermal stimuli. The NS neurons had greater responses and showed less adaptation than the HPC neurons in response to these stimuli, and they encoded stimulus intensity better. Comparison of the normalized response profiles of all 28 nociceptive lamina I STT neurons, independent of cell classification, revealed 2 subgroups that differed significantly: “Maintained” cells with responses that remained above 50% of the initial peak rate during stimulation and “Adapting” cells with responses that quickly declined to <50%. The Maintained neurons encoded the intensity of the mechanical stimuli better than the Adapting neurons, based on ratiometric functions. A k-means cluster analysis of all 28 cells distinguished the identical two subgroups. These categories corresponded closely to the NS and HPC categories: Maintained cells were mostly NS neurons (10 NS, 3 HPC), and Adapting cells were mostly HPC neurons (4 NS, 11 HPC). Thus the present data are consistent with the distinctions between A-fiber and C-fiber nociceptors observed previously, because A-fiber nociceptors are the predominant input to NS lamina I STT neurons and C-fiber nociceptors are the predominant input to HPC neurons. These findings support the view that NS, but perhaps not HPC, lamina I STT neurons have a role in the pain caused by maintained mechanical stimuli and contribute to the sensations of “first” pain and “sharpness.” Nonetheless, none of the units studied showed increasing responses during the stimuli, suggesting a role for other ascending neurons or forebrain integration in the augmenting pain produced by maintained mechanical stimulation.

Inhibition of ADP-Induced Responses in Human Platelets by Agents Elevating the Cyclic AMP Level: Comparison of Aggregation and Shape Change

1984 ◽  
Vol 52 (03) ◽  
pp. 333-335 ◽  
Author(s):  
Vider M Steen ◽  
Holm Holmsen
Keyword(s):  
Inhibitory Action ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Shape Change ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Inhibitory Effects ◽  
Early Step ◽  
Stimulus Response ◽  
Sequential Relationship

SummaryThe inhibitory effect of cAMP-elevating agents on shape change and aggregation in human platelets was studied to improve the understanding of the sequential relationship between these two responses.Human platelet-rich plasma was preincubated for 2 min at 37° C with prostaglandin E1 or adenosine, agents known to elevate the intracellular level of cAMP. Their inhibitory effects on ADP-induced shape change and aggregation were determined both separately and simultaneously. The dose-inhibition patterns for shape change and aggregation were similar for both PGE1 and adenosine. There was no distinct difference between the inhibitory action of these two inhibitors.These observations suggest that elevation of the intracellular concentration of cAMP interferes with an early step in the stimulus-response coupling that is common for aggregation and shape change.

The Behaviour and Neuromuscular System of Gonactinia Prolifera, A Swimming Sea-Anemone

1971 ◽  
Vol 55 (3) ◽  
pp. 611-640
Author(s):  
ELAINE A. ROBSON
Keyword(s):  
Electrical Stimulation ◽  
Mechanical Stimulation ◽  
Motor Units ◽  
Nerve Cells ◽  
Sea Anemone ◽  
Neuromuscular System ◽  
Sea Anemones ◽  
Nerve Net ◽  
Local Contraction ◽  
Electric Shocks

1. In Gonactinia well-developed ectodermal muscle and nerve-net extend over the column and crown and play an important part in the anemone's behaviour. 2. Common sequences of behaviour are described. Feeding is a series of reflex contractions of different muscles by means of which plankton is caught and swallowed. Walking, in the form of brief looping steps, differs markedly in that it continues after interruptions. Anemones also swim with rapid tentacle strokes after contact with certain nudibranch molluscs, strong mechanical disturbance or electrical stimulation. 3. Swimming is attributed to temporary excitation of a diffuse ectodermal pacemaker possibly situated in the upper column. 4. From the results of electrical and mechanical stimulation it is concluded that the endodermal neuromuscular system resembles that of other anemones but that the properties of the ectodermal neuromuscular system require a new explanation. The size and spread of responses to electric shocks vary with intensity, latency is variable and there is a tendency to after-discharge. There is precise radial localization, for example touching a tentacle or the column causes it to bend towards or away from the stimulus. 5. A model to explain these and other features includes multipolar nerve cells closely linked to the nerve-net which would act as intermediate motor units, causing local contraction of the ectodermal muscle. This scheme can be applied to other swimming anemones but there is no evidence that it holds for sea anemones generally.

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