Development of tolerance to antinociceptive effects of an intrathecal morphine/clonidine combination in rats

1995 ◽  
Vol 351 (6) ◽  
pp. 618-623 ◽  
Author(s):  
John L. Plummer ◽  
Patricia L. Cmielewski ◽  
Stephen Tallents ◽  
Pauline De La M. Hall ◽  
John Odontiadis ◽  
...  
Keyword(s):  
Intrathecal Morphine ◽  
Antinociceptive Effects ◽  
Development Of Tolerance

Blockade of α1 subtype GABAA receptors attenuates the development of tolerance to the antinociceptive effects of midazolam in rats

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Lakeisha A. Lewter ◽  
Lalit K. Golani ◽  
James M. Cook ◽  
Jun-Xu Li
Keyword(s):  
Gabaa Receptors ◽  
Antinociceptive Effects ◽  
Development Of Tolerance

Alteration of calcitonin gene related peptide and its receptor binding sites during the development of tolerance to μ and δ opioids

1995 ◽  
Vol 73 (7) ◽  
pp. 1089-1095 ◽  
Author(s):  
D. P. Ménard ◽  
D. van Rossum ◽  
S. Kar ◽  
R. Quirion
Keyword(s):  
Spinal Cord ◽  
Binding Sites ◽  
Specific Interaction ◽  
Calcitonin Gene Related Peptide ◽  
Opioid Agonist ◽  
Pain Mechanisms ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Antinociceptive Effects ◽  
Development Of Tolerance

Calcitonin gene related peptide (CGRP), one of the most abundant peptides in the spinal cord, is localized in primary afferents and released following nociceptive stimuli. Its colocalization and corelease with substance P, a well-known nociceptive neuropeptide, support the importance of CGRP in pain mechanisms. However, its distinctive function in that regard remains to be fully established. Recently, we reported that increases in CGRP-like immunostaining and decrements in specific 125I-labelled human CGRPα ([125I]hCGRPα) binding sites in the spinal cord were correlated with the development of tolerance to the spinal antinociceptive action of a μ opioid agonist, morphine. The goal of the present study was to investigate whether the development of tolerance to other classes of opioids, namely, δ and κ agonists, can also alter CGRP-like immunostaining and receptors in the rat spinal cord. The antinociceptive effects of all opioids were monitored by the tail-immersion test. Tolerance to their antinociceptive properties was induced by the infusion for 7 days of μ (morphine sulfate, 7.5 μg/h), δ ([D-Pen2,D-Pen5]enkephalin (DPDPE), 2.0 μg/h), and κ (U-50488H, 10.0 μg/h) related agonists at the spinal level (L4), using osmotic minipumps. We confirmed that rats chronically treated with morphine showed significant decreases in [125I]CGRPα binding in laminae I, II, and III of the L4 spinal cord, while CGRP-like immunostaining was increased in these same laminae. Similar effects were observed following a treatment with the δ agonist, DPDPE, while the κ agonist, U-50488H, apparently only slightly decreased [125I]CGRPα binding in lamina II. Binding in other laminae and CGRP-like immunostaining were not affected. These results suggest a specific interaction between spinal CGRP systems and the development of tolerance to the spinal antinociceptive effects of μ- and δ-related agonists.Key words: opioid tolerance, calcitonin gene related peptide, sensory neurons, immunostaining, receptor autoradiography.

Importance of sex and relative efficacy at the µ opioid receptor in the development of tolerance and cross-tolerance to the antinociceptive effects of opioids

2001 ◽  
Vol 158 (2) ◽  
pp. 154-164 ◽  
Author(s):  
Andrew Barrett ◽  
Charles Cook ◽  
Jolan Terner ◽  
Rebecca Craft ◽  
Mitchell Picker
Keyword(s):  
Opioid Receptor ◽  
Relative Efficacy ◽  
Cross Tolerance ◽  
Antinociceptive Effects ◽  
Development Of Tolerance

scholarly journals N-Acylethanolamine Acid Amidase Inhibition Potentiates Morphine Analgesia and Delays the Development of Tolerance

2021 ◽  
Author(s):  
Mauro Congiu ◽  
Laura Micheli ◽  
Michele Santoni ◽  
Claudia Sagheddu ◽  
Anna Lisa Muntoni ◽  
...  
Keyword(s):  
Opioid Analgesic ◽  
Morphine Tolerance ◽  
Mechanical Stimuli ◽  
Chronic Morphine ◽  
Analgesic Effects ◽  
Electrophysiological Recordings ◽  
Antinociceptive Effects ◽  
Hydrolyzing Enzymes ◽  
Development Of Tolerance

AbstractOpioids are essential drugs for pain management, although long-term use is accompanied by tolerance, necessitating dose escalation, and dependence. Pharmacological treatments that enhance opioid analgesic effects and/or attenuate the development of tolerance (with a desirable opioid-sparing effect in treating pain) are actively sought. Among them, N-palmitoylethanolamide (PEA), an endogenous lipid neuromodulator with anti-inflammatory and neuroprotective properties, was shown to exert anti-hyperalgesic effects and to delay the emergence of morphine tolerance. A selective augmentation in endogenous PEA levels can be achieved by inhibiting N-acylethanolamine acid amidase (NAAA), one of its primary hydrolyzing enzymes. This study aimed to test the hypothesis that NAAA inhibition, with the novel brain permeable NAAA inhibitor AM11095, modulates morphine’s antinociceptive effects and attenuates the development of morphine tolerance in rats. We tested this hypothesis by measuring the pain threshold to noxious mechanical stimuli and, as a neural correlate, we conducted in vivo electrophysiological recordings from pain-sensitive locus coeruleus (LC) noradrenergic neurons in anesthetized rats. AM11095 dose-dependently (3–30 mg/kg) enhanced the antinociceptive effects of morphine and delayed the development of tolerance to chronic morphine in behaving rats. Consistently, AM11095 enhanced morphine-induced attenuation of the response of LC neurons to foot-shocks and prevented the attenuation of morphine effects following chronic treatment. Behavioral and electrophysiological effects of AM11095 on chronic morphine were paralleled by a decrease in glial activation in the spinal cord, an index of opioid-induced neuroinflammation. NAAA inhibition might represent a potential novel therapeutic approach to increase the analgesic effects of opioids and delay the development of tolerance.

The Role of Hydrogen Sulfide in the Development of Tolerance and Dependence to Morphine in Mice

2020 ◽  
pp. 1-7
Author(s):  
Zeynep Cetin ◽  
Ozgur Gunduz ◽  
Ruhan D. Topuz ◽  
Dikmen Dokmeci ◽  
Hakan C. Karadag ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Physical Dependence ◽  
Morphine Tolerance ◽  
Morphine Dependence ◽  
Tail Flick ◽  
Pain Mechanisms ◽  
Antinociceptive Effects ◽  
Synthase Inhibitor ◽  
Development Of Tolerance

<b><i>Objective:</i></b> Hydrogen sulfide is an endogenous gaseous mediator that has been indicated to have a role in pain mechanisms. In this study, we aimed to detect brain and spinal cord hydrogen sulfide levels during different phases of tolerance and dependence to morphine and to determine the effects of inhibition of endogenous hydrogen sulfide production on the development of tolerance and dependence. <b><i>Methods:</i></b> Morphine tolerance and dependence was developed by subcutaneous injection of morphine (10 mg/kg) twice daily for 12 days. Physical dependence was determined by counting the jumps for 20 min, which is a withdrawal symptom occurring after a single dose of naloxone (5 mg/kg) administered intraperitoneally (i.p.). Propargylglycine (30 mg/kg, i.p.), a cystathionine-γ-lyase inhibitor, and hydroxylamine (12.5 mg/kg, i.p.), a cystathionine-β-synthase inhibitor, were used as hydrogen sulfide synthase inhibitors. The tail-flick and hot-plate tests were used to determine the loss of antinociceptive effects of morphine and development of tolerance. <b><i>Results:</i></b> It was found that chronic and acute uses of both propargylglycine and hydroxylamine prevented the development of tolerance to morphine, whereas they had no effect on morphine dependence. Chronic and acute administrations of hydrogen sulfide synthase inhibitors did not exert any difference in hydrogen sulfide levels in brain and spinal cords of both morphine-tolerant and -dependent animals. <b><i>Conclusion:</i></b> It has been concluded that hydrogen sulfide synthase inhibitors may have utility in preventing morphine tolerance.

Does Intrathecal Morphine in the Treatment of Cancer Pain Induce the Development of Tolerance?

Neurosurgery ◽  
1998 ◽  
Vol 42 (1) ◽  
pp. 44-50 ◽  
Author(s):  
Brigitte Sallerin-Caute ◽  
Yves Lazorthes ◽  
Olivier Deguine ◽  
Bernard Francés ◽  
Jean-Claude Verdié ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Intrathecal Morphine ◽  
Development Of Tolerance

Lack of supra-additivity of antinociceptive effects of intrathecal morphine and intrathecal clonidine in rats

Pain ◽  
1990 ◽  
Vol 41 ◽  
pp. S125 ◽  
Author(s):  
J.L. Plummer ◽  
P.L. Cmielewski ◽  
G.K. Gourlay ◽  
H. Owen ◽  
M.J. Cousins
Keyword(s):  
Intrathecal Morphine ◽  
Antinociceptive Effects ◽  
Intrathecal Clonidine

Interaction of Intrathecally Infused Morphine and Lidocaine in Rats (Part II) 

1998 ◽  
Vol 89 (6) ◽  
pp. 1464-1470 ◽  
Author(s):  
Yoji Saito ◽  
Megumi Kaneko ◽  
Yumiko Kirihara ◽  
Shinichi Sakura ◽  
Yoshihiro Kosaka
Keyword(s):  
Local Anesthetics ◽  
Intrathecal Morphine ◽  
Challenge Test ◽  
Group Development ◽  
Morphine Tolerance ◽  
Tail Flick ◽  
Cross Tolerance ◽  
Antinociceptive Effects ◽  
Induced Tolerance ◽  
Intrathecal Infusion

Background There has been little information regarding the effects of local anesthetics on tolerance to opioids, although chronic use of combination of opioids and local anesthetics is popular for pain control. This study was designed to examine the effects of lidocaine on morphine tolerance to somatic and visceral antinociception. Methods Rats received a continuous intrathecal infusion of morphine (0.3-10 microg x kg(-1) x h(-1)), lidocaine (30-1000 microg x kg(-1). h(-1)), a combination of those, or saline. After 6- day infusion, intrathecal morphine challenge test (5 microg/10 microl) was performed, and time-response curve was constructed to assess the magnitude of tolerance. The tail flick (TF) test and colorectal distension (CD) test were used to measure somatic and visceral antinociceptive effects, respectively. Results Antinociceptive effects in the TF and CD tests caused by morphine challenge were reduced (P &lt; 0.01) in the morphine infused groups. The magnitude of the tolerance was inversely associated with the amount of morphine infused. Lidocaine infusion induced no different change in the morphine challenge test from that seen in the saline infusion group. Development of tolerance was greater in morphine 3 microg x kg(-1) h(-1) than in morphine 0.75 microg x kg(-1) x h(-1) + lidocaine 150 microg x kg(-1) x h(-1) despite their similar antinociceptive effects during intrathecal infusion. The infusion of a low dose of morphine (0.3 microg kg(-1) x h(-1)) did not reduce the antinociceptive effects in the challenge test. Conclusion Lidocaine in combination with morphine does not reduce tolerance to morphine nor develop cross-tolerance. The intrathecal infusion of morphine induced tolerance to somatic and visceral antinociception in a dose-dependent fashion.

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