Neurotoxicity of Intrathecally Administered Bupivacaine Involves the Posterior Roots/Posterior White Matter and Is Milder Than Lidocaine in Rats

Takenami, Tamie; Yagishita, Saburo; Murase, Setsuko; Hiruma, Hiromi; Kawakami, Tadashi; Hoka, Sumio

doi:10.1016/j.rapm.2005.05.005

Cited by 31 publications

(24 citation statements)

References 34 publications

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“…After recovery from surgery, verification of chronically implanted lumbar catheters was determined by observing temporary hindlimb paralysis resulting from an intrathecal injection of 20 l (0.5%) of xylocaine-MPF. No histological abnormalities are produced after single lumbar intrathecal injections of 2% lidocaine or 0.5% bupivacaine (0.12 l/g body weight) in the rat (Takenami et al, 2005).…”

Section: Methodsmentioning

confidence: 96%

Spinal μ-Opioid Receptor-Expressing Dorsal Horn Neurons: Role in Nociception and Morphine Antinociception

Kline¹,

Wiley²

2008

J. Neurosci.

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The role of spinal cord -opioid receptor (MOR)-expressing dorsal horn neurons in nociception and morphine analgesia is incompletely understood. Using intrathecal dermorphin-saporin (Derm-sap) to selectively destroy MOR-expressing dorsal horn neurons, we sought to determine the role of these neurons in (1) normal baseline reflex nocifensive responses to noxious thermal stimulation (hotplate, tail flick) and to persistent noxious chemical stimulation (formalin) and (2) the antinociceptive activity of intrathecal and systemic morphine in the same tests. Lumbar intrathecal Derm-sap (500 ng) produced (1) partial loss of lamina II MOR-expressing dorsal horn neurons, (2) no effect on MOR-expressing dorsal root ganglion neurons, and (3) no change in baseline tail-flick and hotplate reflex nocifensive responses. Derm-sap treatment attenuated the antinociceptive action of both intrathecal and systemic morphine on hotplate responses. Derm-sap treatment had two effects in the formalin test: (1) increased baseline nocifensive responding and (2) reduced antinociceptive action of systemic morphine. We conclude that MOR-expressing dorsal horn neurons (1) are not essential for determining nocifensive reflex responsiveness to noxious thermal stimuli, (2) are necessary for full antinociceptive action of morphine (intrathecal or systemic) in these tests, and (3) play a significant role in the endogenous modulation of reflex nocifensive responses to persistent pain in the formalin test. Thus, one would predict that altering the activity of MOR-expressing dorsal horn neurons would be antinociceptive and of interest in the search for new approaches to management of chronic pain.

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Section: Methodsmentioning

confidence: 96%

Spinal μ-Opioid Receptor-Expressing Dorsal Horn Neurons: Role in Nociception and Morphine Antinociception

Kline¹,

Wiley²

2008

J. Neurosci.

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“…In our previous study using the same protocol, we reported the induction of histological lesions by bupivacaine, mepivacaine, and prilocaine (each at eight times), 11 lidocaine (3.7 times), 9 and tetracaine (four times) 10 higher than their clinical respective concentrations. In the present study, the concentration experiment indicated that procaine, levobupivacaine, and ropivacaine did not induce lesions even when used at ten times the clinical concentrations, suggesting that these three agents are less toxic than the drugs tested previously.…”

Section: Discussionmentioning

confidence: 93%

“…bupivacaine for the central nervous and cardiovascular systems in animals 4,5 and humans. [6][7][8] In a series of studies, we determined the neurotoxicities of lidocaine, tetracaine, bupivacaine, mepivacaine, prilocaine, and procaine [9][10][11][12] in a rat spinal model. These studies showed that all these agents, with the exception of procaine, were neurotoxic, with lesions displaying common features irrespective of the anesthetic agent and affecting mainly axons of the dorsal root entry zone.…”

Section: Résumémentioning

confidence: 99%

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Intrathecally administered ropivacaine is less neurotoxic than procaine, bupivacaine, and levobupivacaine in a rat spinal model

Takenami

Wang

Nara

et al. 2012

Can J Anesth/J Can Anesth

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Purpose The aim of this study was to compare the neurotoxicity of intrathecal procaine, bupivacaine, levobupivacaine, and ropivacaine in an animal model. Methods The study comprised two experiments. In the concentration experiment, rats (n = 78) were administered 0.12 lLÁg -1 body weight (BW) of 2% or 20% procaine, 0.5% or 5% bupivacaine, 0.5% or 5% levobupivacaine, or 0.5% or 5% ropivacaine. Based on the findings, the doses were increased by volume in the subsequent volume experiment using 0.12, 0.24, or 0.48 lLÁg -1 BW of 6% procaine, 6% levobupivacaine, or 6% ropivacaine (n = 79). Walking behaviour and sensory threshold were analyzed, and a histological examination of the spinal cord, posterior and anterior roots, and cauda equina was performed. Results The concentration experiment showed abnormalities only in the 5% bupivacaine group, and these abnormal findings were in the posterior root (PR) and posterior column (PC). The volume experiment revealed that procaine 0.24 lLÁg -1 was neurotoxic, mainly affecting the PR. At 0.48 lLÁg -1 , severe injury was observed in the PR and PC in all six procaine rats and four of six levobupivacaine rats, while milder injury was limited to the PR in one of six ropivacaine rats, which differed significantly from the former two groups (P = 0.006 and P = 0.014, respectively). Electron microscopy showed axonal degeneration. Conclusion All four local anesthetics seemed to cause identical neurotoxic lesions commencing in the PR and Author contributions Tamie Takenami designed and initiated this study, took part in all aspects of the experiments, collected data for statistical analysis, and wrote the manuscript. Guoqin Wang performed statistical tests, assisted with the statistical analysis, and proposed the method of statistical analysis to validate the injury score. Yoshihiro Nara assisted with catheterization, drug injection, and securing the catheters. He also performed evaluations for the ambulation and paw stimulation tests. Sayano Fukushima assisted with the assessment of the injury scores. Saburo Yagishita verified the pathological changes. Hiromi Hiruma and Tadashi Kawakami allowed use of their laboratory during the study and reviewed the manuscript. Hiromi Hiruma, Tadashi Kawakami, and Hirotsugu Okamoto offered their advice. 123Can J Anesth/J Can Anesth (2012) 59: 456-465 DOI 10.1007/s12630-012-9685-9 extending to the PC by axonal degeneration. Bupivacaine appeared to be the most neurotoxic of the four drugs, and the neurotoxicity at higher doses increased by volume with procaine [ levobupivacaine [ ropivacaine. RésuméObjectif L'objectif de cette e´tude e´tait de comparer la neurotoxicite´intrathe´cale de la procaı¨ne, de la bupivacaı¨ne, de la le´vobupivacaı¨ne et de la ropivacaı¨ne dans un mode`le animal. Méthodes L'e´tude a comporte´deux expe´rimentations. Dans une expe´rience sur la concentration, des rats (n = 78) ont reçu 0,12 lLÁg -1 de poids corporel de procaı¨ne a`2 % ou 20 %, de bupivacaı¨ne a`0,5 % ou 5 %, de le´vobupivacaı¨ne a`0,5 % ou 5 % ou de...

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“…; on the other hand, its disadvantages are the following: Its application requires time and expertise; there is application error related post interventional risk of neurological sequels; local anesthetic toxicity; technique related complications; and vets' lack of adequate knowledge 2,7,8, 13 . It has been stated that complications such as hypotension, bradycardia, vomiting, cardiac failure, meningitis and meningismus, paralysis, urinary retention and the cauda equina syndrome can be seldom manifested following the application of spinal anesthesia .…”

Section: 8-13mentioning

confidence: 99%

Köpeklerde İki Farklı Konsantrasyondaki Bupivacaine HCl ve Ropivacaine HCl ile Oluşturulan Spinal Anestezinin Klinik, Bazı Hemodinamik ve Histopatolojik Etkilerinin Karşılaştırılması

Yayla¹,

Kiliç²

2009

Kafkas Univ Vet Fak Derg

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SummaryThe aim of this study was to evaluate the side effects of local and systemic clinical, histopathological and hemodynamics by use of isobaric and hyperbaric bupivacaine in different concentrations during spinal anesthesia which has been a common use within the past few years. The study material consisted of 23 healthy stray dogs with dissimilar sex, age and body weight as well as bupivacaine hydrochloride containing Marcaine® %0.5 (Astra Zenaca, Turkey) and Marcaine® Spinal Heavy %0.5 (Astra Zenaca, Turkey), and ropivacaine hydrochloride containing Naropin® 7.5mg/ml (Astra Zenaca, Germany) so as to create the state of spinal anesthesia. A total of 5 different groups were formed where each study group consisted of 5 dogs and the control group consisted of 3 dogs. The groups were as follows: Aa (Marcaine), Ab (Marcaine® Spinal Heavy), Ba (Naropin®), Bb (Naropin® + Dekstroz) and C (Dekstroz). During the anesthesia; blood pressure, pulse and respiratory rates were measured in all groups. Besides, needle punctures were applied from time to time. The animals were euthanized following a one-week long hospitalization. Then, the parts of the spinal cords on which injections were applied were taken off and investigated histopathologically. In this study no significant were observed with regard to the use of ropivacaine HCl and bupivacaine HCl and their clinical, hemodynamic and histopathologic side effects; on the other hand, bupivacaine HCl was found to be considerably superior to ropivacaine HCl regarding the anesthesia duration and depth.

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Neurotoxicity of Intrathecally Administered Bupivacaine Involves the Posterior Roots/Posterior White Matter and Is Milder Than Lidocaine in Rats

Cited by 31 publications

References 34 publications

Spinal μ-Opioid Receptor-Expressing Dorsal Horn Neurons: Role in Nociception and Morphine Antinociception

Spinal μ-Opioid Receptor-Expressing Dorsal Horn Neurons: Role in Nociception and Morphine Antinociception

Intrathecally administered ropivacaine is less neurotoxic than procaine, bupivacaine, and levobupivacaine in a rat spinal model

Köpeklerde İki Farklı Konsantrasyondaki Bupivacaine HCl ve Ropivacaine HCl ile Oluşturulan Spinal Anestezinin Klinik, Bazı Hemodinamik ve Histopatolojik Etkilerinin Karşılaştırılması

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