The Effects of Different Monoaminergic Antidepressants on the Analgesia Induced by Spinal Cord Adrenal Medullary Transplants in the Formalin Test in Rats

Ortega-Álvaro, A.; Gibert-Rahola, J.; Mellado-Fernandez, Manuel L.; Chover, A.J.; Micó, Juan Antonio

doi:10.1213/00000539-199704000-00022

Cited by 19 publications

(4 citation statements)

References 19 publications

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“…For example, the nonselective NE/5-HT reuptake inhibitor amitriptyline, when given chronically, increases the analgesia induced by spinal cord adrenal medullary transplants in rats, whereas fluvoxamine (SSRI) and desipramine (NERI) do not [25]. Furthermore, different antidepressants show different regulatory activities in adrenal PBR.…”

Section: Discussionmentioning

confidence: 99%

Tissue-Specific Regulation of the Peripheral Benzodiazepine Receptor by Antidepressants and Lithium

Leschiner¹,

Weizman²,

Shoukrun³

et al. 2000

Neuropsychobiology

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Peripheral benzodiazepine receptors (PBR) have been identified in peripheral organs as well as in brain glial cells. PBR differ from central benzodiazepine receptors (CBR) in their lack of coupling to the γ-aminobutyric acid receptors and the chloride ion channels. We investigated the effect of 21 days administration, followed by 7 days withdrawal, of fluvoxamine (10 mg/kg), desipramine (10 mg/kg) and lithium carbonate (25 mg/kg) on PBR and CBR binding characteristics in male Sprague-Dawley rats. All three agents significantly increased PBR density in the testes and adrenals. All tested drugs induced a significant decrease in PBR density in the kidney and liver. After withdrawal, PBR density remained decreased in the liver in all three groups and in the kidneys of the desipramine- and lithium-treated animals. In the cerebral cortex, CBR density increased in response to all three agents, whereas PBR density decreased significantly in response to desipramine and lithium carbonate. Chronic treatment with fluvoxamine, desipramine and lithium carbonate is apparently associated with a modulation in PBR expression in the testes, adrenals, kidneys, liver and brain, and in CBR expression in brain. The relevance of these tissue-selective alterations to the antidepressive and/or anxiolytic effects of these agents, or their adverse effects, still needs to be determined.

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Section: Discussionmentioning

confidence: 99%

Tissue-Specific Regulation of the Peripheral Benzodiazepine Receptor by Antidepressants and Lithium

Leschiner¹,

Weizman²,

Shoukrun³

et al. 2000

Neuropsychobiology

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“…Previous studies in our and other laboratories have demonstrated that transplants of adrenal medullary chromaffin cells into the subarachnoid space of the spinal cord can attenuate pain responses in a variety of animal models and offers a promising avenue for clinical pain management (Brewer and Yezierski 1998;Buchser et al 1996;Burgess et al 1996;Décosterd et al 1998;Hains et al 1998;Hama and Sagen 1993;Lazorthes et al 1995;Ortega-Alvaro et al 1997;Sagen et al 1990;Siegan and Sagen 1997;Vaquero et al 1991;Winnie et al 1993;Yu et al 1998). Although the transplanted cells appear to produce some of their antinociceptive effects via local release of pain-reducing analgesic agents, including catecholamines and opioid peptides, into the host spinal CSF (Sagen and Kemmler 1989;Sagen et al 1991), recent studies have indicated that these transplants can also produce neuroplastic changes in the pain processing circuitry of the spinal cord, including restoration of spinal inhibitory neurons and decreased c-fos activation in response to persistent pain (Ibuki et al 1997;Sagen and Wang 1995).…”

Section: Discussionmentioning

confidence: 98%

“…Recent findings suggest that prolonged noxious stimulation results in release of endogenousTransplantation of adrenal medullary chromaffin cells in the subarachnoid space of the spinal cord has been shown to reduce pain behaviors in several animal models, including inflammatory pain (Ortega-Alvaro et al 1997;Sagen et al 1990;Siegan and Sagen 1997;Vaquero et al 1991;Wang and Sagen 1995), neuropathic pain (Décosterd et al 1998;Ginzburg and Seltzer 1990; Sagen 1993, 1994), and central pain models (Brewer and Yezierski 1998;Hains et al 1998;Yu et al 1998). This has led to the initiation of clinical trials at several centers, with promising outcomes (Buchser et al 1996;Burgess et al, 1996;Lazorthes et al 1995;Winnie et al 1993).…”

mentioning

confidence: 99%

Alterations in Endogenous Brain β-Endorphin Release by Adrenal Medullary Transplants in the Spinal Cord

Yadid

Zangen

Herzberg

et al. 2000

Neuropsychopharmacology

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While transplants of adrenal medullary cells into the spinal subarachnoid space may produce antinociception via inhibition of spinal pain transmission pathways, alterations at higher central nervous system (CNS) centers have not been addressed. Recent findings suggest that prolonged noxious stimulation results in release of endogenousTransplantation of adrenal medullary chromaffin cells in the subarachnoid space of the spinal cord has been shown to reduce pain behaviors in several animal models, including inflammatory pain (Ortega-Alvaro et al. 1997;Sagen et al. 1990;Siegan and Sagen 1997;Vaquero et al. 1991;Wang and Sagen 1995), neuropathic pain (Décosterd et al. 1998;Ginzburg and Seltzer 1990; Sagen 1993, 1994), and central pain models (Brewer and Yezierski 1998;Hains et al. 1998;Yu et al. 1998). This has led to the initiation of clinical trials at several centers, with promising outcomes (Buchser et al. 1996;Burgess et al., 1996;Lazorthes et al. 1995;Winnie et al. 1993). Since chromaffin cells produce and secrete several potential pain-reducing neuroactive substances, including opioid peptides and catecholamines, a possible mechanism for this pain reduction is via inhibition of spinal pain transmission pathways. In support for this, adrenal medullary transplants in the rat lumbar spinal subarachnoid space suppress flinching responses 23 , NO . 6 in the formalin pain model, an effect which is partially reversed by opioid antagonist naloxone or ␣ -adrenergic antagonist phentolamine (Siegan and Sagen 1997).While local spinal actions of cellular implants have been the focus of the majority of previous studies, effects on higher central nervous system (CNS) pain processing centers have been largely ignored. In particular, recent findings by our group have demonstrated markedly increased levels of endogenous ␤ -endorphin secretion in the hypothalamic arcuate nucleus coincident with pain behaviors in response to hindpaw injections of formalin (Zangen et al. 1998). As the arcuate nucleus is the principal source of this potent opioid peptide in the CNS (Bach 1997), this finding may be indicative of a compensatory mechanism in response to prolonged noxious stimuli. In support for this, noxious stimuli or persistent pain have been shown to increase activity in the arcuate nucleus as indicated by increased c-fos (Bullitt 1990;Pan et al. 1994), 2-deoxyglucose (Mao et al. 1993, and blood flow (Morrow et al. 2000) in that region. In addition, intense activation of spinal nociceptive pathways by intrathecal capsaicin results in increased ␤ -endorphin release in brain lateral ventricular perfusates (Bach and Yaksh 1995a).The hypothalamic arcuate nucleus may also play a role in endogenous analgesic responses. For example, this region is activated by analgesic low frequency electroacupuncture (Lee and Beitz 1993;Pan et al. 1994;Takeshige et al. 1992; Wang et al. 1990a,b;Zhang et al. 1996), and local stimulation of the arcuate nucleus or ␤ -endorphin microinjection can reduce pain responses to noxious stimuli (Bach and Yak...

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“…Most of this work has focused on the transplantation of adrenal medullary chromaffin cells in the spinal subarachnoid space, as these cells produce numerous agents with analgesic or antinociceptive activity, including opioid peptides, catecholamines, and endogenous Nmethyl-D-aspartate (NMDA) antagonists. Adrenal medullary tissue or isolated chromaffin cell transplants have shown efficacy in various preclinical pain models, including the formalin test [1][2][3][4][5], chronic inflammation [6][7][8], neuropathic pain models [9][10][11][12][13][14], central pain models [15][16][17][18], and wind-up [19]. Our laboratory at the University of Illinois at Chicago (UIC) published the first papers on the use of this approach in preclinical acute rodent pain models in 1986 [20][21].…”

Section: Adrenal Medullary Transplants For Pain: Previous Clinical Exmentioning

confidence: 99%

Cellular therapies for spinal cord injury: What will the FDA need to approve moving from the laboratory to the human?

Sagen¹

2003

JRRD

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Abstract-The transplantation of living cells and tissues to restore function and/or provide therapeutic molecules has been an active and ongoing area of research interest for over 25 years. Several of these potential therapies have reached initial clinical trials, and it is likely that applications will continue to expand, and that novel and improved approaches will be explored over the next several years. In the past, many of these experimental approaches were tested in early clinical trials without the oversight of regulatory agencies such as the Food and Drug Administration. However, as novel cellular therapies move from preclinical laboratory findings to the clinical arena, researchers and regulators face new and continually evolving issues and uncertainties involving long-term safety and efficacy. Using adrenal medullary transplantation in the spinal cord for pain as an example, this review presents an overview of past and current regulatory guidelines for moving these promising, novel cellular transplantation therapies from the laboratory to the human.

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The Effects of Different Monoaminergic Antidepressants on the Analgesia Induced by Spinal Cord Adrenal Medullary Transplants in the Formalin Test in Rats

Cited by 19 publications

References 19 publications

Tissue-Specific Regulation of the Peripheral Benzodiazepine Receptor by Antidepressants and Lithium

Tissue-Specific Regulation of the Peripheral Benzodiazepine Receptor by Antidepressants and Lithium

Alterations in Endogenous Brain β-Endorphin Release by Adrenal Medullary Transplants in the Spinal Cord

Cellular therapies for spinal cord injury: What will the FDA need to approve moving from the laboratory to the human?

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