Sensitization of Spinal Neurons by Non-noxious Stimuli in the Awake but Not Anesthetized State 

1995 ◽  
Vol 82 (1) ◽  
pp. 267-275 ◽  
Author(s):  
Juan F. Herrero ◽  
Max P. Headley
Keyword(s):  
Neuronal Excitability ◽  
Dynamic Range ◽  
Conscious State ◽  
Spinal Neurons ◽  
Mechanical Conditioning ◽  
Sensory Pathways ◽  
Before And After ◽  
Nociceptive Afferents ◽  
Peripheral Trauma ◽  
Noxious Stimuli

Background The observation that peripheral trauma causes enhanced spinal neuronal excitability has provided the scientific rationale for the concept of "pre-emptive analgesia." The premise has been that only noxious stimuli cause sensitization in sensory pathways, but this premise has not been tested in the conscious state. Methods Responses of single spinal neurons were recorded in instrumented sheep that were untrained and free from drugs or recent surgery, in either fully conscious or halothane-anesthetized states. Receptive field (RF) size was measured before and after non-noxious mechanical conditioning stimulation. Results Noxious conditioning stimuli in anesthetized sheep caused enlargement of RF areas, as expected. Conditioning with nonpainful scratching or other stimuli was without effect in anesthetized animals; in marked contrast, it caused enlargement of RF size in conscious animals, in which 29 of 33 wide dynamic range units but only 1 of 12 low-threshold mechanoreceptive neurons were affected. Conclusions Sensitization of spinal sensory neurons evidently is a process that is not restricted to pathologic pain states but rather that occurs under normal physiologic conditions independent of painful stimuli. The significance of such sensitization processes therefore needs reevaluation. The sensitization triggered by non-nociceptive afferents is likely to be opioid-resistant and therefore may contribute to the rather disappointing results seen in several clinical trials of "pre-emptive analgesia."

scholarly journals Evaluation of direct reading photoionization detector performance under various operational parameters

2021 ◽  
Vol 8 (2) ◽  
pp. 123-128
Author(s):  
Amir Hossein Khoshakhlagh ◽  
Farideh Golbabaei ◽  
Mojtaba Beygzadeh ◽  
Francisco Carrasco-Marín ◽  
Seyed Jamaleddin Shahtaheri
Keyword(s):  
Relative Humidity ◽  
Dynamic Range ◽  
Reference Method ◽  
Operational Parameters ◽  
Direct Reading ◽  
Detector Performance ◽  
Vapor Detection ◽  
Sample Concentration ◽  
Photoionization Detector ◽  
Before And After

Background: A hand-held portable direct-reading monitor, including photoionization detector (PID) is renowned for its good sensitivity, considerable dynamic range, and nondestructive vapor detection ability in comparison to the tardy response of the PID in gas chromatography (GC), which its application has been restricted. In this study, the performance of a PID system (MultiRAE Lite) was evaluated as a replacement of GC in the measurement of toluene in a dynamic adsorption system. Methods: The test was done at different relative humidity levels (30%, 50%, and 80%), temperatures (21, 30, 40° C), and toluene concentrations (20, 100, 200, and 400 ppm). Results: The PID achieved 48% of all measurements meeting the comparison criterion. The results showed that the performance of the PID could be altered by the variables. The best performance of the PID was at temperature of 21° C, the relative humidity of 50%, and concentration of 200 ppm with the percentage of readings achieving the criterion of comparison to 58%, 54%, and 52%, respectively. The averages of the PID readings (mean ± SD at 200 ppm= 207.9 ± 8.7) were higher than the reference method measurements averages (mean ± SD at 200 ppm= 203.5 ± 5.8). The regression analysis of the toluene results from the PID and the reference method results indicated that the measurements were significantly correlated (r2 = 0.93). Conclusion: According to the results, the device response is linear. Therefore, the findings are acceptable in adsorption studies. In this way, the measurement of the sample concentration should be performed using the same instrument before and after the reactor in order to calculate the adsorption efficiency.

Placing pain on the sensory map: Classic papers by Ed Perl and colleagues

2007 ◽  
Vol 97 (3) ◽  
pp. 1871-1873 ◽  
Author(s):  
Peggy Mason
Keyword(s):  
Dorsal Horn ◽  
Marginal Zone ◽  
Superficial Dorsal Horn ◽  
Spinal Neurons ◽  
Nociceptive Neurons ◽  
Unmyelinated Fibers ◽  
Noxious Stimuli ◽  
Sensory Map ◽  
Thermal Stimuli ◽  
Classic Papers

This essay looks at two papers published by Ed Perl and co-workers that identified specifically nociceptive neurons in the periphery and superficial dorsal horn. Bessou P and Perl ER. Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J Neurophysiol 32: 1025–1043 1969. Christensen BN and Perl ER. Spinal neurons specifically excited by noxious or thermal stimuli: marginal zone of the dorsal horn. J Neurophysiol 33: 293–307 1970.

Grouping of somatosensory neurons in the spinal cord and the gracile nucleus of the rat by cluster analysis

1994 ◽  
Vol 72 (6) ◽  
pp. 2590-2597 ◽  
Author(s):  
J. W. Leem ◽  
B. H. Lee ◽  
W. D. Willis ◽  
J. M. Chung
Keyword(s):  
Cluster Analysis ◽  
Dorsal Horn ◽  
Dynamic Range ◽  
High Threshold ◽  
Spinothalamic Tract ◽  
Wide Dynamic Range ◽  
Gracile Nucleus ◽  
Noxious Stimuli ◽  
Thermal Stimuli ◽  
Wide Dynamic Range Neurons

1. A set of 11 cutaneous stimuli defined previously to differentiate among different types of cutaneous sensory receptors in the rat hindpaw was also effective in differentially activating second-order sensory neurons in the dorsal horn and the gracile nucleus of rats. 2. All sampled units were responsive to more than 1 of the 11 stimuli. However, none responded to innocuous warming or cooling stimuli. Therefore further analysis was restricted to responses to nine of the selected stimuli. 3. Cluster analysis of the responses to nine selected innocuous and noxious mechanical stimuli and noxious thermal stimuli yielded seven classes that seemed functionally distinct from each other: a class of high-threshold neurons, three classes of convergent (wide dynamic range) neurons, a class of a mixture of poorly responsive neurons and neurons receiving Pacinian inputs, and two classes of low-threshold neurons. 4. High-threshold neurons responded predominantly to noxious mechanical and thermal stimuli and presumably received an input from both mechanically and thermally sensitive nociceptors. These cells were located in the dorsal horn, and some were spinothalamic tract cells. Wide dynamic range neurons were excited by innocuous and noxious stimuli, but better by noxious stimuli. These classes of cells were either in the dorsal horn (some were spinothalamic tract cells) or in the nucleus gracilis.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurotransmitters in the thalamus relaying visceral input to the insular cortex in the rat

2001 ◽  
Vol 281 (5) ◽  
pp. R1665-R1674 ◽  
Author(s):  
Francesco Barnabi ◽  
David F. Cechetto
Keyword(s):  
Amino Acid ◽  
Neuronal Excitability ◽  
Excitatory Amino Acid ◽  
Insular Cortex ◽  
Nmda Antagonist ◽  
Cortical Response ◽  
Evoked Response ◽  
Adrenergic Antagonist ◽  
Before And After ◽  
Specific Antagonist

Neurotransmitters relaying ascending visceral information were examined by comparing the response of neurons in the insular cortex to vagal stimulation (0.8 Hz, 2 mA) before and after neurotransmitter antagonist injections (200 nl) in the ventroposterior parvocellular nucleus of the thalamus (VPpc). Cobalt (10 mM; presynaptic blocker) and kynurenate (100 μM; nonspecific excitatory amino acid antagonist) injections in the VPpc resulted in an attenuation (73–100 and 38–98%, respectively) of the evoked cortical response. Injections of the specific N-methyl-d-aspartate (NMDA) antagonistdl-2-amino-5-phosphonopentanoic acid (200 μM and 2 mM) did not affect the vagally evoked response, whereas the nonspecific non-NMDA antagonist l-glutamic acid diethylester (200 μM) attenuated the vagally evoked response by 66–100%. Three concentrations of thedl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA)-specific antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 and 200 μM and 2 mM) attenuated the vagally evoked cortical response by 29 ± 9, 31 ± 10, and 59 ± 8%, respectively. The more selective AMPA antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (200 μM and 2 mM) inhibited the vagally evoked cortical response by 53 ± 8 and 52 ± 3%, respectively. Phentolamine (0.1 and 1.0 μM), a general α-adrenergic antagonist, and picrotoxin (0.1 and 1.0 μM), a GABAA antagonist, did not affect the vagally evoked response. Atropine, a muscarinic cholinergic antagonist, decreased the vagally evoked response by 40 ± 2% at a concentration of 0.1 μM, but a higher concentration of 1.0 μM had no effect. These results indicate that the non-NMDA excitatory amino acid receptor is necessary for the relay of visceral information in the VPpc. Muscarinic receptors may modulate visceral neuronal excitability in the VPpc, although the exact interaction between the inhibitory (m2) and excitatory (m3 or m5) muscarinic receptor types found in the thalamus is not known.

scholarly journals Presynaptic dopamine deficit in minimally conscious state patients following traumatic brain injury

Brain ◽  
2019 ◽  
Vol 142 (7) ◽  
pp. 1887-1893 ◽  
Author(s):  
Esteban A Fridman ◽  
Joseph R Osborne ◽  
Paul D Mozley ◽  
Jonathan D Victor ◽  
Nicholas D Schiff
Keyword(s):  
Clinical Trial ◽  
Dopamine Transporter ◽  
Dopamine Release ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Before And After ◽  
Post Traumatic ◽  
Central Thalamus ◽  
Minimally Conscious ◽  
Injured Patients

Abstract Dopaminergic stimulation has been proposed as a treatment strategy for post-traumatic brain injured patients in minimally conscious state based on a clinical trial using amantadine, a weak dopamine transporter blocker. However, a specific contribution of dopaminergic neuromodulation in minimally conscious state is undemonstrated. In a phase 0 clinical trial, we evaluated 13 normal volunteers and seven post-traumatic minimally conscious state patients using 11C-raclopride PET to estimate dopamine 2-like receptors occupancy in the striatum and central thalamus before and after dopamine transporter blockade with dextroamphetamine. If a presynaptic deficit was observed, a third and a fourth 11C-raclopride PET were acquired to evaluate changes in dopamine release induced by l-DOPA and l-DOPA+dextroamphetamine. Permutation analysis showed a significant reduction of dopamine release in patients, demonstrating a presynaptic deficit in the striatum and central thalamus that could not be reversed by blocking the dopamine transporter. However, administration of the dopamine precursor l-DOPA reversed the presynaptic deficit by restoring the biosynthesis of dopamine from both ventral tegmentum and substantia nigra. The advantages of alternative pharmacodynamic approaches in post-traumatic minimally conscious state patients should be tested in clinical trials, as patients currently refractory to amantadine might benefit from them.

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.

Changes in tonic descending inhibition of spinal neurons with articular input during the development of acute arthritis in the cat

1991 ◽  
Vol 66 (3) ◽  
pp. 1021-1032 ◽  
Author(s):  
H. G. Schaible ◽  
V. Neugebauer ◽  
F. Cervero ◽  
R. F. Schmidt
Keyword(s):  
Acute Inflammation ◽  
Dynamic Range ◽  
Receptive Fields ◽  
Response Threshold ◽  
Mechanical Stimuli ◽  
Spinal Neurons ◽  
Descending Inhibition ◽  
Intact State ◽  
Wdr Neurons ◽  
Alpha Chloralose

1. In 15 alpha-chloralose-anesthetized cats we studied the presence of tonic descending inhibition (TDI) of spinal neurons with input from the knee and its modulation during an acute inflammation of this joint. TDI of spinal neurons with articular input was assessed by applying reversible cold blocks to the lower thoracic cord. The amount of descending inhibition was estimated from the induction and/or increase of resting discharges and of the responses to mechanical stimuli to the knee and other structures during the transitory and reversible blocks. In each experiment one or a few neurons were investigated while the joint was in normal condition [altogether 15 nociceptive-specific (NS) and 6 wide-dynamic-range (WDR) neurons]. One of the neurons was then selected for long-term recordings during which an acute inflammation in the knee was induced by the intra-articular injection of kaolin and carrageenan. Before and during developing arthritis, cold blocks were applied to examine whether the amount of TDI would change during the inflammatory process. 2. The neurons with input from the normal knee were under TDI because application of the cold block induced or increased resting discharges and the responses to noxious compression of the knee and the adjacent thigh and lower leg. In 10 of 15 NS neurons, the response threshold was lowered into the innocuous range. In 9 of 17 cells tested, the excitatory receptive field expanded to the ipsilateral paw, and 4 neurons became inhibited by paw compression. Seven of 18 neurons tested revealed inhibitory receptive fields on the contralateral leg during cold block. The neurons were located in laminae IV-VII. 3. Fourteen neurons were continuously monitored during development of inflammation, and changes in the effectiveness of TDI were assessed by blocking the cord before and during the development of arthritis. In most neurons baseline resting activity in the intact state of the cord increased while the arthritis developed. This inflammation-evoked enhancement of resting discharges was more pronounced during periods of spinalization. Consequently, the differences between the resting discharges in the cold-blocked and the intact state were progressively enhanced in arthritis. 4. After induction of arthritis, the responses to compression of the knee joint increased in the intact state as well as during cold blocks. In 11 of 14 neurons, the differences between the responses in the spinal and intact state were progressively enlarged during the development of inflammation. A similar result was obtained for flexion of the injected knee.(ABSTRACT TRUNCATED AT 400 WORDS)

Changes in Response Properties and Receptive Fields of Spinal Dorsal Horn Neurons in Rats after Surgical Incision in Hairy Skin

2005 ◽  
Vol 102 (1) ◽  
pp. 141-151 ◽  
Author(s):  
Mikito Kawamata ◽  
Masayuki Koshizaki ◽  
Steven G. Shimada ◽  
Eichi Narimatsu ◽  
Yuji Kozuka ◽  
...  
Keyword(s):  
Dynamic Range ◽  
Receptive Fields ◽  
Gamma Aminobutyric Acid ◽  
Wide Dynamic Range ◽  
Surgical Incision ◽  
Dorsal Horn Neurons ◽  
Hairy Skin ◽  
Noxious Stimuli ◽  
Made In ◽  
Wide Dynamic Range Neurons

Background Mechanical hyperalgesia and allodynia associated with chemical irritant application are mediated by spinal high-threshold (HT) as well as wide-dynamic-range neurons as a result of "central sensitization." Because the pathophysiology of pain is thought to differ depending on the type of injury and may vary between hairy and glabrous skin, the authors examined changes in properties of spinal dorsal horn neurons after surgical incisions in hairy skin of rats to obtain insights into the mechanisms of postoperative pain. Methods Withdrawal responses to punctate mechanical stimulation and gentle brushing were measured in awake rats in an area adjacent to the injured site (primary area) and in an area 2 cm from the injured site (secondary area) after 1-cm longitudinal incisions through the hairy skin, fascia, and muscle had been made in the hindquarters. In a separate study, responses of spinal wide-dynamic-range, HT, and low-threshold neurons to nonnoxious and noxious stimuli were recorded before and after similar incisions had been made in the centers of their receptive fields. Effects of spinal application of the gamma-aminobutyric acid A receptor antagonist bicuculline (15 microg) on responses of HT neurons were then studied. Results Awake rats showed primary and secondary hyperalgesia to punctate mechanical stimulation 30 min after the incision and thereafter for 4 days and 1 day, respectively. Mechanical allodynia associated with brush stimulation was only seen in the primary area 30 min after the incision and thereafter for 1 day. The incision resulted in increases in activity of wide-dynamic-range neurons (receptive field sizes and responses to both innocuous and noxious stimuli). HT neurons did not respond to innocuous stimulation and showed very small increases or no changes in receptive field size and responses to noxious stimuli after the incision. However, the majority of HT neurons began to respond to innocuous stimuli after application of bicuculline (15 microg/50 microl) to the spinal cord. Conclusions The results suggest that wide-dynamic-range neurons are responsible for behavioral hyperexcitability after surgical incision but that HT neurons are not involved in the hyperexcitability, despite the fact that HT neurons are capable of responding to innocuous stimuli by reversal of gamma-aminobutyric acid-mediated inhibition.

Cutaneous responsiveness of lumbar spinal neurons in awake and halothane-anesthetized sheep

1995 ◽  
Vol 74 (4) ◽  
pp. 1549-1562 ◽  
Author(s):  
J. F. Herrero ◽  
P. M. Headley
Keyword(s):  
Dynamic Range ◽  
High Threshold ◽  
Relative Distribution ◽  
Control Mechanisms ◽  
Spinal Neurons ◽  
Halothane Anesthesia ◽  
Sensory Stimuli ◽  
Low Threshold ◽  
Wdr Neurons ◽  
Lumbar Spinal

1. To compare the responsiveness of lumbar spinal neurons to peripheral sensory stimuli under normal physiological conditions and under halothane anesthesia, we performed a study in sheep that were prepared chronically. This permitted recordings to be made in the same animals either when they were awake and free from recent surgery, drugs, and training and only partially restrained or when they were anesthetized with halothane. 2. We recorded 261 units in dorsal and ventral horns under conscious conditions. Of these, 19% had no detectable receptive field (RF) and 44% had responses dominated by proprioceptive inputs; these units were not investigated in detail. The remaining 96 neurons (37%) had clearly defined cutaneous RFs. Of these, most (72%) had wide-dynamic-range (WDR; convergent, multireceptive) properties, 19% were low-threshold mechanoreceptive (LTMR), and 9% were high-threshold mechanoreceptive (HTMR). These units with cutaneous RFs were investigated in greater detail. 3. The spontaneous activity under these awake conditions was low (< 4 spikes/s) for nearly all units in all three categories. The mechanical threshold of the most sensitive (central) part of the cutaneous RF was assessed with von Frey bristles. Thresholds were < 5 mN for all LTMR neurons, < 1-30 mN for WDR neurons, and > 80 mN for HTMR neurons. The size of the low-threshold cutaneous RFs was significantly larger for WDR neurons (mean 46 cm2) and HTMR neurons (45 cm2) than for LTMR neurons (24 cm2). The RFs were distributed all over the ipsilateral hindlimb. Large RFs were mostly proximal, whereas small RFs were distributed relatively evenly over the limb. 4. Recordings were made from a further 165 units while the animals were under halothane anesthesia. With 86 neurons having cutaneous peripheral RFs, the proportions having LTMR, HTMR, or WDR characteristics were very similar to those in awake animals. Under halothane the ongoing activity of WDR units was slightly (but significantly) less. The threshold to von Frey bristle stimulation was significantly higher only for WDR units, in both dorsal and ventral horns. The mean size of cutaneous RFs was significantly larger in all classes of units recorded under halothane anesthesia. For WDR units this was true for cells in both dorsal and ventral horns. This effect on mean values was due to a larger proportion of units with very large fields under anesthesia, particularly in the dorsal horn. 5. Comparison of the data from conscious animals with published results of acute experiments indicates that acute recording conditions do not distort the relative distribution and resting characteristics of these three functional categories of lumbar spinal neurons as much as might have been expected. 6. Halothane does not have major effects on the resting sensory responsiveness of spinal neurons with cutaneous RFs. The increase in RF area, which contrasts with most results from acute studies, is likely to be due to a dampening of descending inhibitory control mechanisms.

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