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One-Year Chromaffin Cell Allograft Survival in Cancer Patients With Chronic Pain: Morphological and Functional Evidence

Identifieur interne : 000F80 ( Istex/Corpus ); précédent : 000F79; suivant : 000F81

One-Year Chromaffin Cell Allograft Survival in Cancer Patients With Chronic Pain: Morphological and Functional Evidence

Auteurs : Jean C. Bés ; Jean Tkaczuk ; Kimberly A. Czech ; Mathieu Tafani ; Raymond Bastide ; Claude Caratero ; George D. Pappas ; Yves Lazorthes

Source :

RBID : ISTEX:2205CC8D5803B03DB7C4E16B9CF7D1CAE66F387A

English descriptors

Abstract

The control of chronic pain through transplantation of chromaffin cells has been reported over the past few years. Analgesic effects are principally due to the production of opioid peptides and catecholamines by chromaffin cells. Clinical trials have been reported with allografts consisting of whole-tissue fragments implanted into the subarachnoid space of the lumbar spinal cord [14, 19, 36]. In the present study, allogeneic grafts were successfully used to control chronic pain in two patients over a period of 1 yr based on patient reported pain scores, morphine intake, and CSF levels of Met-enkephalin. Macroscopic examination at autopsy located the transplanted tissue fragments in the form of multilobulated nodules at the level of the spinal axis and cauda equina. Immunocytochemical microscopy showed neuroendocrine cells are positive for chromagranin A (CGA), and enzymes tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DβH). The results suggest that there is a relationship between analgesic effect, Met-enkephalin levels in CSF, and the presence of chromaffin cells surviving in spinal subarachnoid space.

Url:
DOI: 10.1016/S0963-6897(97)00161-9

Links to Exploration step

ISTEX:2205CC8D5803B03DB7C4E16B9CF7D1CAE66F387A

Le document en format XML

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<note type="content">Fig. 1: (A) Patient-reported pain score (from 0 = no pain to 10 = the most intense pain). P1: patient 1; P2: patient 2; Single arrow = initial chromaffin cell graft; double arrows = second transplant. (B) The complementary daily intrathecal morphine intake (mg/24 h). (C) The Met-enkephalin release into the CSF (pg/mL). The mean basal level of CSF Met-enkephalin was done for 10 nongrafted patients (hatched areas). This was the reference value for the CSF Met-enkephalin rate of grafted patients.</note>
<note type="content">Fig. 2: Autopsy specimens from P1 show the dispersion of grafted tissue fragments (A, whole spinal cord, reduced, ruler length 16 cm) from the injections site (L4/L5). Note (arrows), multilobulated nodules of irregular size (B), clusters of adrenal medullary tissue between the roots of the cauda equina (C), and one nodular location in the inner aspect of the dura mater (D) (mag: B, 3×; C, 4×; D, 4×).</note>
<note type="content">Fig. 3: Low-power photomicrograph (A) of a section through two fragments of adrenal medullary tissue isolated from the lumbar-sacral roots and immunostained for chromagranin A (CGA) reactivity. At higher magnification (B), CGA-positive remnants revealed the rounded morphology of chromaffin cells and cellular and collagenous elements (arrowheads) between these nodular formations (mag: A, 320×; B, 2200×).</note>
<note type="content">Fig. 4: Low-power photomicrograph (A) of dopamine-β-hydroxylase (DβH)-stained section through the graft site. (B) Chromaffin cells immunohistochemically stained with tyrosine hydroxylase (TH) antibody with a rhodamine-linked secondary antibody marker. Note the intensity of TH labeling. (mag: A, 160×: B, 1200×).</note>
<note type="content">Fig. 5: The electron microscopy study (×30,000) show an important tissue alteration with degenerative chromaffin cells in necrotic zone but also the evidence of some secretory granuli.</note>
<note type="content">Table 1: The complementary intrathecal morphine intake (mg/24 h) and the CSF Met-enkephalin release (pg/mL) data</note>
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<ce:simple-para>The control of chronic pain through transplantation of chromaffin cells has been reported over the past few years. Analgesic effects are principally due to the production of opioid peptides and catecholamines by chromaffin cells. Clinical trials have been reported with allografts consisting of whole-tissue fragments implanted into the subarachnoid space of the lumbar spinal cord
<ce:cross-refs refid="BIB14 BIB19 BIB36">[14, 19, 36]</ce:cross-refs>
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<abstract lang="en">The control of chronic pain through transplantation of chromaffin cells has been reported over the past few years. Analgesic effects are principally due to the production of opioid peptides and catecholamines by chromaffin cells. Clinical trials have been reported with allografts consisting of whole-tissue fragments implanted into the subarachnoid space of the lumbar spinal cord [14, 19, 36]. In the present study, allogeneic grafts were successfully used to control chronic pain in two patients over a period of 1 yr based on patient reported pain scores, morphine intake, and CSF levels of Met-enkephalin. Macroscopic examination at autopsy located the transplanted tissue fragments in the form of multilobulated nodules at the level of the spinal axis and cauda equina. Immunocytochemical microscopy showed neuroendocrine cells are positive for chromagranin A (CGA), and enzymes tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DβH). The results suggest that there is a relationship between analgesic effect, Met-enkephalin levels in CSF, and the presence of chromaffin cells surviving in spinal subarachnoid space.</abstract>
<note type="content">Section title: Original Contributions</note>
<note type="content">Fig. 1: (A) Patient-reported pain score (from 0 = no pain to 10 = the most intense pain). P1: patient 1; P2: patient 2; Single arrow = initial chromaffin cell graft; double arrows = second transplant. (B) The complementary daily intrathecal morphine intake (mg/24 h). (C) The Met-enkephalin release into the CSF (pg/mL). The mean basal level of CSF Met-enkephalin was done for 10 nongrafted patients (hatched areas). This was the reference value for the CSF Met-enkephalin rate of grafted patients.</note>
<note type="content">Fig. 2: Autopsy specimens from P1 show the dispersion of grafted tissue fragments (A, whole spinal cord, reduced, ruler length 16 cm) from the injections site (L4/L5). Note (arrows), multilobulated nodules of irregular size (B), clusters of adrenal medullary tissue between the roots of the cauda equina (C), and one nodular location in the inner aspect of the dura mater (D) (mag: B, 3×; C, 4×; D, 4×).</note>
<note type="content">Fig. 3: Low-power photomicrograph (A) of a section through two fragments of adrenal medullary tissue isolated from the lumbar-sacral roots and immunostained for chromagranin A (CGA) reactivity. At higher magnification (B), CGA-positive remnants revealed the rounded morphology of chromaffin cells and cellular and collagenous elements (arrowheads) between these nodular formations (mag: A, 320×; B, 2200×).</note>
<note type="content">Fig. 4: Low-power photomicrograph (A) of dopamine-β-hydroxylase (DβH)-stained section through the graft site. (B) Chromaffin cells immunohistochemically stained with tyrosine hydroxylase (TH) antibody with a rhodamine-linked secondary antibody marker. Note the intensity of TH labeling. (mag: A, 160×: B, 1200×).</note>
<note type="content">Fig. 5: The electron microscopy study (×30,000) show an important tissue alteration with degenerative chromaffin cells in necrotic zone but also the evidence of some secretory granuli.</note>
<note type="content">Table 1: The complementary intrathecal morphine intake (mg/24 h) and the CSF Met-enkephalin release (pg/mL) data</note>
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