Spinal Adrenergic and Cholinergic Receptor Interactions Activated by Clonidine in Postincisional Pain

2003 ◽  
Vol 98 (5) ◽  
pp. 1237-1242 ◽  
Author(s):  
Frédéric Duflo ◽  
Dawn Conklin ◽  
Xinhui Li ◽  
James C. Eisenach
Keyword(s):  
Cholinergic Receptor ◽  
Cholinergic Receptors ◽  
Antisense Oligodeoxynucleotide ◽  
Mechanical Stimuli ◽  
Adrenergic Agonists ◽  
Adrenoceptor Antagonist ◽  
Receptor Interactions ◽  
Plantar Incision ◽  
Subtype A ◽  
Intrathecal Clonidine

Background Previous pharmacologic and molecular studies suggest that the alpha(2)-adrenoceptor subtype A is the target for spinally administered alpha(2)-adrenergic agonists, i.e., clonidine, for pain relief. However, intrathecally administered alpha(2) C antisense oligodeoxynucleotide was recently reported to decrease antinociception induced by clonidine in the rat, suggesting non-A sites may be important as well. The current study sought to determine the subtype of alpha(2) adrenoceptors activated by clonidine in a rodent model for human postoperative pain, and to examine its interaction with spinal cholinergic receptors. Methods Postoperative hypersensitivity was produced in rats by plantar incision of the hind paw and punctuate mechanical stimuli were applied around the wound 24 h after surgery. Effects of intrathecal clonidine and 2-(2,6-diethylphenylamino)-2-imidazoline (ST91) on withdrawal thresholds to the stimulus were determined. To examine the adrenoceptor subtype and its interaction with spinal cholinergic receptors, animals were intrathecally pretreated with vehicles BRL44408 (an alpha(2) A subtype-preferring antagonist), ARC239 (an alpha(2) non-A subtype-preferring antagonist), atropine (a muscarinic antagonist), and mecamylamine (a nicotinic antagonist). Results Intrathecal ST91 showed a significantly greater efficacy when compared with clonidine. The analgesic effect of clonidine was diminished by pretreatment with either adrenoceptor antagonist, whereas the effect of ST91 was solely blocked by ARC239 pretreatment. Atropine and mecamylamine abolished the effect of clonidine effect but not the effect of ST91. Conclusions Both alpha(2) A and alpha(2) non-A adrenoceptors, as well as spinal cholinergic activation, are important to the antihypersensitivity effect of clonidine after surgery. ST91 is more efficacious in this model than clonidine and relies entirely on alpha(2) non-A adrenoceptors.

scholarly journals Beta-adrenergic and M-cholinergic receptor interactions characteristics in the pathogenesis of bronchial obstructive pulmonary diseases

2020 ◽  
Author(s):  
Anna Eremenko ◽  
K. A. Zykov
Keyword(s):  
Cholinergic Receptor ◽  
Cholinergic Receptors ◽  
Pulmonary Diseases ◽  
Chronic Obstructive ◽  
Main Role ◽  
Treatment Regimens ◽  
M3 Receptors ◽  
Receptor Interactions ◽  
Functional Antagonism ◽  
The One

Crosstalk between beta-2-adrenoceptor and M- cholinoreceptors in the airway plays one of the main role in the pathogenesis of bronchoobstructive diseases. The interaction of M3-cholinergic receptors and beta2-receptors in the lungs can be characterized as functional antagonism. M3 activation can lead to desensitization of beta2 receptors. Beta2 receptors also limit the action of M3 receptors in various ways. In this case, M2 cholinergic receptors act as autoreceptors. On the one hand, they limit bronchoconstriction caused by a change in the conformation of the M3 cholinergic receptor, and on the other hand, they are able to suppress the excessive bronchorelaxating effect that occurs when beta2 receptor is activated. Knowledge of the crosstalk mechanisms can help to understanad the pathogenesis of bronchial obstructive diseases, optimize existing treatment regimens for chronic obstructive disease (COPD) and bronchial asthma (BA)

Plasticity in Action of Intrathecal Clonidine to Mechanical but Not Thermal Nociception after Peripheral Nerve Injury

2003 ◽  
Vol 99 (1) ◽  
pp. 199-204 ◽  
Author(s):  
Xavier Paqueron ◽  
Dawn Conklin ◽  
James C. Eisenach
Keyword(s):  
Nerve Injury ◽  
Cholinergic Neurons ◽  
Radiant Heat ◽  
Cholinergic Receptor ◽  
Intrathecal Administration ◽  
Thermal Stimulus ◽  
Thermal Nociception ◽  
Nociceptive Transmission ◽  
Withdrawal Threshold ◽  
Intrathecal Clonidine

Background Intrathecal clonidine reduces tactile allodynia in animal models of neuropathic pain, and this effect is blocked by atropine. However, the role of tonic spinal cholinergic activity and its interaction with alpha2-adrenergic systems in normal and neuropathic conditions and to different sensory methods has not been systematically examined. The authors examined cholinergic receptor involvement in thermal and mechanical sensitivity in normal and neuropathic animals and its interaction with intrathecal clonidine. Methods Normal rats and rats that received L5/L6 spinal nerve ligation were tested with acute radiant heat, paw pressure, and punctate mechanical stimulation before and after the intrathecal administration of saline, the muscarinic receptor antagonist, atropine, or a toxin to destroy cholinergic neurons, and then after intrathecal clonidine. Results Atropine, the cholinergic neuronal toxin, and saline did not alter baseline withdrawal thresholds. In nerve-injured rats, neither saline nor atropine altered antinociception from clonidine to a thermal stimulus, but atropine reduced the effect of clonidine to von Frey filament withdrawal threshold (34 +/- 5.6 vs. 14 +/- 5.8 g [mean +/- SEM], saline vs. atropine; P < 0.05) and to withdrawal threshold to paw pressure after clonidine (174 +/- 18 g vs. 137 +/- 16 g, saline vs. atropine; P < 0.05). Conclusions These data suggest that after nerve injury, mechanical but not thermal antinociception from intrathecal clonidine relies on a muscarinic interaction, because only mechanical antinociception was antagonized by atropine. These results do not favor a regulation of nociceptive transmission by a tonic release of acetylcholine in nerve-injured rats.

scholarly journals Adrenergic and Cholinergic Receptors of Cerebral Microvessels

1981 ◽  
Vol 1 (3) ◽  
pp. 329-338 ◽  
Author(s):  
Sami I. Harik ◽  
Virendra K. Sharma ◽  
John R. Wetherbee ◽  
Robert H. Warren ◽  
Shailesh P. Banerjee
Keyword(s):  
Adrenergic Receptors ◽  
Specific Binding ◽  
Cholinergic Receptors ◽  
Biologically Active ◽  
Adrenergic Agonists ◽  
Muscarinic Cholinergic Receptors ◽  
Cerebral Microvessels ◽  
Binding Characteristics ◽  
Muscarinic Cholinergic ◽  
Β Adrenergic Receptors

The presence of α- and β-adrenergic and muscarinic cholinergic receptors in cerebral microvessels of the rat and pig was assessed by ligand binding techniques. The results demonstrate the presence of specific binding to α2- and β-adrenergic receptors but no appreciable specific binding to α1-adrenergic or muscarinic cholinergic receptors. β-Adrenergic receptors of pig cerebral microvessels are similar to those of the brain and other organs in their binding characteristics to the tritiated ligand and in their stereospecificity of binding to the biologically active isomers of β-adrenergic agonists. Further evidence derived from the differential potency of binding displacement by the various β-adrenergic agonists and selective β1- and β2-adrenergic antagonists indicates that β-adrenergic receptors of pig cerebral microvessels are mostly of the β2-subtype.

Contraction and [3H]QNB binding in collagenase isolated fundic smooth muscle cells

1983 ◽  
Vol 245 (2) ◽  
pp. G270-G276
Author(s):  
E. R. Seidel ◽  
L. R. Johnson
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cholinergic Receptor ◽  
Gastric Fundus ◽  
Cholinergic Receptors ◽  
Muscarinic Agonists ◽  
Muscarinic Cholinergic Receptors ◽  
Binding Characteristics ◽  
Muscarinic Cholinergic

Smooth muscle cells from the guinea pig gastric fundus were isolated by successive collagenase digestions. Tritiated quinuclidinyl benzilate [( 3H]QNB) was used to study the binding characteristics of the muscarinic cholinergic receptors on these cells. Each cell bound 8.3 X 10(-19) mol of QNB, and a concentration of QNB of 0.19 nM was required to label one-half of the binding sites. This suggests a concentration of about 500,000 muscarinic cholinergic receptors per smooth muscle cell. The muscarinic cholinergic receptor antagonists atropine and scopolamine inhibited QNB binding with a 50% inhibiting concentration (IC50) in the nanomolar range, whereas the agonists acetylcholine (ACh), oxotremorine, and carbamylcholine had IC50S in the micromolar range. Hill coefficients (nH) for antagonists approached unity, but agonists displayed fractional nH. Exposure of cells to cholinergic muscarinic agonists resulted in dose-dependent decreases in cell length. The concentration of agonist required to induce half-maximal contractions (ED50) was 8.3 X 10(-12) M for ACh and 6.3 X 10(-13) M for oxotremorine. Atropine (10(-9) M) decreased the sensitivity to ACh, increasing the ED50 for ACh-induced contractions to 1.2 X 10(-10) M. These results suggest the existence of muscarinic receptor heterogeneity for cholinergic agonists but not for antagonists.

Changes in Tissue pH and Temperature after Incision Indicate Acidosis May Contribute to Postoperative Pain

2004 ◽  
Vol 101 (2) ◽  
pp. 468-475 ◽  
Author(s):  
Young Cheol Woo ◽  
Soo Seog Park ◽  
Alberto R. Subieta ◽  
Timothy J. Brennan
Keyword(s):  
Postoperative Pain ◽  
Skin Temperature ◽  
Gastrocnemius Muscle ◽  
Contralateral Side ◽  
Mechanical Stimuli ◽  
Ph Change ◽  
Tissue Ph ◽  
Pain Behaviors ◽  
Guarding Behavior ◽  
Plantar Incision

Background Incisional pain is a common form of acute pain. Previously, the authors studied persistent pain behaviors caused by incisions, using animal models for postoperative pain. In this study, the authors measured tissue pH and hind paw temperature before and after incision to understand factors that may activate and sensitize nociceptors in the incision. Methods Rats underwent a plantar incision, a gastrocnemius muscle incision, or a cutaneous paraspinal incision. For the hind paw incision, pain behaviors were measured. Tissue pH was measured using a pH-sensitive needle electrode in halothane-anesthetized rats. The pH in the incision was compared to a corresponding control site on the contralateral side of the rat or to the sham-operated group. Results Plantar tissue pH was 7.16 +/- 0.04 in sham-operated rats. Ten minutes after plantar incision, tissue pH was decreased to 6.91 +/- 0.20 (P < 0.05), and this decrease was sustained through 60 min after incision, when pH was 6.99 +/- 0.06 (P < 0.05). Tissue pH values were 6.95, 6.90, 6.89, and 6.95 (P < 0.05 vs. sham) 4 h and 1, 2, and 4 days after incision, respectively. On postoperative day 7, when plantar pH was same as for the control side (7.13 +/- 0.05), guarding behavior, heat responses, and responses to mechanical stimuli recovered. Outside the incised area in the hind paw, tissue pH was normal. Tissue pH was significantly correlated with all pain behaviors. In the gastrocnemius muscle, tissue pH was 7.14 +/- 0.7 in the sham-operated side. Ten minutes after incision, tissue pH was 6.54 +/- 0.12 (P < 0.05), and muscle pH remained decreased through 60 min after gastrocnemius incision when pH was 6.76 +/- 0.17 (P < 0.05). Tissue pH was also significantly decreased (P < 0.05) on day 1 (6.96 vs. 7.20) and day 4 (7.06 vs. 7.18) after gastrocnemius incision but was not reduced on postoperative day 8 (7.11 vs. 7.15). A paraspinal incision also decreased tissue pH in the hairy skin of the rat compared with the preincision value. Hind paw skin temperature did not change after incision. Conclusion A decrease in pH occurs immediately after incision and is sustained for at least 4 days. During the period of decreased tissue pH, pain behaviors are evident. When the tissue pH returns to normal, pain behaviors are diminished. The decreased pH is localized at the incision site and not to areas surrounding the incision. Decreased pH likely contributes to nociceptor sensitization and pain related behaviors after incision. The magnitude of the pH change varies among tissues. An increase in hind paw skin temperature does not play a role in these pain-related behaviors.

Characterization of myometrial desensitization to β-adrenergic agonists

1990 ◽  
Vol 68 (10) ◽  
pp. 1377-1384 ◽  
Author(s):  
Brian A. Dayes ◽  
Stephen J. Lye
Keyword(s):  
Adrenergic Receptors ◽  
Contractile Activity ◽  
Significant Inhibition ◽  
Scatchard Analysis ◽  
Continuous Exposure ◽  
Partial Recovery ◽  
Adrenergic Agonists ◽  
Camp Content ◽  
Adrenoceptor Antagonist ◽  
Β Adrenergic Receptors

Continuous exposure of ovine myometrial strips exposed to isoproterenol (10 μM) resulted in only transient inhibition with contractions returning within 60 min. Rechallenging these strips with isoproterenol failed to induce inhibition, confirming the occurrence of desensitization. In contrast, exposure of myometrial tissue to isoproterenol for only 5 min did not result in desensitization. Myometrial strips exposed to isoproterenol demonstrated a significant increase in cAMP content associated with inhibition of contractile activity and a subsequent fall in cAMP content upon desensitization. Elevation of endogenous cAMP levels by either inhibition of cAMP-dependent phosphodiesterase activity (0.5 mM isobutylmethylxanthine, in ovine strips) or direct activation of adenylyl cyclase (10 μM forskolin, in rat strips) induced a rapid and significant inhibition of myometrial contractile activity in desensitized tissue. Scatchard analysis of the binding of the β-adrenoceptor antagonist, [125I]iodocyanopindolol, revealed a significant reduction in the concentration of β-adrenergic receptors (but no change in binding affinity) in desensitized myometrial tissue. Incubation of desensitized tissue with fresh buffer for 3 h induced only a partial recovery in responsiveness to isoproterenol. These data suggest that prolonged, but not acute, exposure of the myometrium to β-adrenergic agonists induces a state of desensitization that is associated with a down-regulation of β-adrenoceptors but maintenance of postreceptor function.Key words: myometrium, contraction, β-adrenergic receptors, β-antagonists.

Cholinergic receptor interactions and their effects on long-term memory processing

1981 ◽  
Vol 215 (1-2) ◽  
pp. 177-185 ◽  
Author(s):  
James F. Flood ◽  
Dennis W. Landry ◽  
Murray E. Jarvik
Keyword(s):  
Cholinergic Receptor ◽  
Long Term Memory ◽  
Term Memory ◽  
Memory Processing ◽  
Receptor Interactions

Inhibition of drinking in water-deprived rats by combined central angiotensin II and cholinergic receptor blockade

1978 ◽  
Vol 234 (1) ◽  
pp. F41-F47 ◽  
Author(s):  
W. E. Hoffman ◽  
U. Ganten ◽  
M. I. Phillips ◽  
P. G. Schmid ◽  
P. Schelling ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Water Intake ◽  
Physiological Role ◽  
Cholinergic Receptor ◽  
Inhibitory Effect ◽  
Cholinergic Receptors ◽  
Sprague Dawley ◽  
Cholinergic Blockade ◽  
Sprague Dawley Rats ◽  
Hereditary Hypothalamic Diabetes Insipidus

The effect of blockade of central angiotensin II (AII) receptors and cholinergic receptors on thirst induced by water deprivation was studied in Sprague-Dawley rats and rats with hereditary hypothalamic diabetes insipidus (DI). Neither central AII nor cholinergic blockade alone affected drinking. Antagonism of both receptors simultaneously, however, significantly inhibited water intake of both Sprague-Dawley and DI rats. This inhibitory effect was not observed in water-deprived, nephrectomized rats. The combined antagonism on water intake was specific, since milk intake in hungry rats was not affected by simultaneous AII and cholinergic blockade. Isorenin concentrations in brain tissue were at control levels in water-deprived, nephrectomized, and non-nephrectomized Sprague-Dawley rats but were increased in water-deprived DI rats. The results suggest that angiotensin and cholinergic receptors in the brain have a physiological role in thirst. Thirst is maintained when either receptor is intact, but reduced when both receptors are inhibited by antagonists. They are independently capable of maintaining thirst.

Peripheral Nerve Injury Alters the α2Adrenoceptor Subtype Activated by Clonidine for Analgesia

2002 ◽  
Vol 97 (3) ◽  
pp. 636-641 ◽  
Author(s):  
Frédéric Duflo ◽  
Xinhui Li ◽  
Carsten Bantel ◽  
Carlo Pancaro ◽  
Michelle Vincler ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Antinociceptive Effect ◽  
Mechanical Stimulus ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Antisense Oligodeoxynucleotide ◽  
Alpha Adrenoceptors ◽  
Alpha Adrenoceptor ◽  
Withdrawal Threshold ◽  
Intrathecal Clonidine

Background Previous studies suggest that the alpha adrenoceptor subtype is the target for spinally administered alpha -adrenergic agonists, clonidine, for pain relief. However, ST 91, a preferential alpha adrenoceptor subtype agonist, induces antinociception, and intrathecally administered alpha antisense oligodeoxynucleotide decreases antinociception induced by clonidine in the rat, suggesting non-A sites may be important as well. Therefore, the authors examined the subtype of alpha adrenoceptor activated by clonidine and ST 91 in normal rats and those with nerve injury-induced hypersensitivity. Methods The same mechanical stimulus was applied to normal rats and those following spinal nerve ligation, and the effect of intrathecal clonidine and ST 91 on withdrawal threshold to the stimulus was determined. To further examine subtypes, animals were spinally pretreated with vehicle, BRL 44408 (an alpha subtype-preferring antagonist), and ARC 239 (an alpha subtype-preferring antagonist). Results In normal animals, clonidine's effect was diminished by pretreatment with either antagonist, whereas ST 91's antinociceptive effect was solely blocked by pretreatment with ARC 239. In nerve-injured animals, the antihypersensitivity action of both clonidine and ST 91 was blocked by administration of ARC 239, whereas BRL 44408 was ineffective. Conclusions These data agree with previous studies supporting that the alpha adrenoceptor is important to the antinociceptive effect of clonidine in normal animals. Nerve injury alters this and results in a total reliance on alpha adrenoceptors.

Sign in / Sign up

Export Citation Format

Share Document