Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of intractable pain with parenteral, subarachnoid, or epidural narcotics is often unsatisfactory due to tolerance and other systemic complications that accompany increasing dosages of these drugs. Other disadvantages include the potential infections with implantable pumps and the inconvenience of repeated narcotic administration. During the past several years, studies at the author's laboratory indicated that transplantation of adrenal medullary tissue or isolated chromaffin cells into the spinal subarachnoid space can significantly reduce pain in several rodent models without resulting in development of tolerance. Adrenal medullary chromaffin cells were selected because they produce high levels of both opioid peptides and catecholamines, agents that independently, and possibly synergistically, reduce pain when injected locally into the spinal subarachnoid space. The adrenal medullary transplants survive for prolonged periods, and continue to produce high levels of both catecholamines and met-enkephalin. These transplants reduce pain in two rodent chronic pain models, an arthritis model and a peripheral neuropathy model, both of which closely resemble human chronic pain syndromes. The success of the animal studies has led to initiation of human clinical trials in patients with chronic cancer pain; results are promising.
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PMID:Chromaffin cell transplants for alleviation of chronic pain. 137 36

Surgical hypophysectomy performed in 18 cases with hormone-dependent carcinoma resulted in tumour regression in 38.8% of the cases, and pain relief in 88%. Neuroadenolysis performed 170 times on 130 cases resulted in pain relief in 94% with hormone-dependent carcinoma, and 70% with non-dependent carcinoma. The clinical investigations, following performance of neuroadenolysis, indicate suppressed pituitary function, significant increase of ACTH, thyrotropin-releasing hormone and vasopressin in the cerebrospinal fluid (CSF), delay of long latencies in somatosensory evoked potential and increased pain threshold of C-fibres. Increase of beta-endorphin in CSF was very brief. Though the exact physiological activity in pain sensation of those peptides other than endorphins still remains obscure, increase of the peptides which are mainly synthesized in the hypothalamopituitary axis, along with suppressed pituitary function, is considered to exert a long-lasting suppressive effect on the mediation and perception of cancer pain through C-fibres and the central nervous system.
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PMID:The pituitary as a target of antalgic treatment of chronic cancer pain: a possible mechanism of pain relief through pituitary neuroadenolysis. 243 39

The purpose of this study was to assess whether xenogeneic tumor cells secreting beta-endorphin and immunologically isolated in polymer capsules could survive and continue to reduce pain when transplanted into the spinal cerebro-spinal fluid (CSF) space of rats. Also, a silicone container for polymer capsules was designed for the clinical application of this method of cell therapy. The mouse tumor cell lines, proopiomelanocortin gene transfected Neuro2A which secrete beta-endorphin, were enclosed in polymer capsules at a density of 5 x 10(6)/mL, and transplanted into the spinal CSF space from the occipito-atlantal junction of male Sprague-Dawley rats. Three analgesiometric tests--the tail pinch test, the hot plate test, and electrical stimulation test--showed that the rats with encapsulated Neuro2A (n = 6) were significantly less sensitive to pain after transplantation than control animals (n = 8). The analgesia induced by the encapsulated cells secreting beta-endorphin was attenuated by the opiate antagonist naloxone. Morphological study revealed that the encapsulated cells survived for 1 mo after transplantation into the CSF space. An in vitro experiment on cultured capsules (3 cm long) with a silicone container (Kaneka Medics Co) showed that the encapsulated Neuro2A (5 x 10(6) mL) could secrete peptides for 1 mo. The results of this study indicate that immunologically isolated xenogeneic tumor cells can secrete opiate in the CSF space, and that a silicone container may help the application of this method to the treatment of cancer pain.
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PMID:Cell therapy with encapsulated xenogeneic tumor cells secreting beta-endorphin for treatment of peripheral pain. 779 96

The purpose of this study was to assess whether xenogeneic tumor cells immunologically isolated in polymer capsules could survive and continue to reduce pain when transplanted into the cerebrospinal fluid (CSF) of rats. The mouse tumor cell lines AtT-20 and gene-transfected Neuro2A, which secrete beta-endorphin, were enclosed in polymer capsules at a density of 5 x 10(6) cells/ml and transplanted into the spinal CSF space of the occipitoatlantal junction in male Sprague-Dawley rats. The analgesiometric tests (tail pinch, hot plate, and electrical stimulation) showed that the five rats with encapsulated AtT-20 or Neuro2A (eight rats) were significantly less sensitive to pain after transplantation than the eight control animals (analysis of variance; p < 0.05). The analgesia induced by encapsulated cells secreting beta-endorphin could be attenuated by the opiate antagonist naloxone, which suggested the involvement of opiate in mediating this response. Morphological study revealed that the cells in polymer capsules survived 1 month after transplantation in the CSF space. In vitro experiments with cultured capsules showed that both encapsulated AtT-20 and Neuro2A secrete peptide for 1 month. The results of this study suggest that immunologically isolated xenogeneic tumor cells can secrete opiate in the CSF space, and this method may be applied to the treatment of cancer pain.
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PMID:Analgesia induced by transplantation of encapsulated tumor cells secreting beta-endorphin. 789 26

A number of pre-clinical studies have demonstrated the value of adrenal medullary allografts in the management of chronic pain. The present longitudinal survey studied 15 patients transplanted for intractable cancer pain after failure of systemic opioids due to the persistence of undesirable side-effects. Before inclusion, all the patients had their pain controlled by daily intrathecal (I-Th) morphine administration. The main evaluation criteria of analgesic activity of the chromaffin cell allograft was the complementary requirement of analgesics and in particular the consumption of I-Th morphine required to maintain effective pain control. Out of the 12 patients who profited from enhanced analgesia with long-term follow-up (average 4.5 months), five no longer required the I-Th morphine (with prolonged interruption of systemic opioids as well), two durably decreased I-Th morphine intake and five were stabilized until the end of their follow-up. Durable decline and stabilization were interpreted as indicative of analgesic activity by comparison with the usual dose escalation observed during disease progression. In most cases, we noted a relationship between analgesic responses and CSF met-enkephalin levels. The results of this phase II open study demonstrate the feasibility and the safety of this approach using chromaffin cell grafts for long-term relief of intractable cancer pain. However, while analgesic efficacy was indicated by the reduction or stabilization in complementary opioid intake, these observations will need to be confirmed in a controlled trial in a larger series of patients.
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PMID:Human chromaffin cell graft into the CSF for cancer pain management: a prospective phase II clinical study. 1086 42

The durable effectiveness of intrathecal morphine administration is well established for the management of intractable cancer pain, after failure of systemic opioids, secondary to the persistence of non-reversible undesirable side effects. Many patients are referred to late in the disease course. This conservative method to control pain of malignant origin must not be reserved for last resort treatment for terminal patients. Intra-cerebro-ventricular morphine administration is a very effective and generally safe method for controlling intractable cancer pain. Because of the chronic implantation of an intra-ventricular catheter this method is somewhat invasive. Its indications remain a simple and effective alternative when the topography of nociceptive pain is diffuse or cephalic. In clinical practice, intrathecal and/or intra-cerebro-ventricular administration of opioids is limited by cost, the need for specialized maintenance and mechanical malfunctions if implantable drug delivery systems, or by the risk of bacterial contamination and ambulatory constraints when repeated daily injections via an intrathecal access port are used. To answer these limitations, cell therapy using intrathecal chromaffin cell allograft is a promising approach for the management of cancer pain refractory to traditional drug therapy and pain lesion surgery. The basic rationale and preclinical studies on experimental pain models have enabled starting prospective clinical trials. Prior to transplantation, handling and preparation of the chromaffin tissue is critical for allograft viability. The initial results of clinical trials with human chromaffin cell grafts from intractable cancer pain have reported long-lasting pain relief, in correlation with met-enkephalin release into the CSF. Convincing evidence will require controlled studies. The limitations of this innovative cell therapy and especially the lack of human adrenal gland availability point to the need for new sources of cells. Perspectives include xenogenic or engineered cell lines.
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PMID:[Management of intractable cancer pain: from intrathecal morphine to cell allograft]. 1108 78

Transplantation of adrenal medullary tissue for terminal cancer pain has been tested clinically, but this approach is not practical for routine use because of the shortage of organ donors and lack of tissue homogeneity. As a first alternative step, we have generated immortalized chromaffin cells over-expressing opioid peptides, namely met-enkephalin. Rat chromaffin cells have been genetically modified with vectors containing expression cassettes with either synthetic met-enkephalin or pro-enkephalin gene coding regions, fused with the nerve growth factor signal peptide for secretion. After stable transfection and differentiation in vitro, met-enkephalin and pro-enkephalin cells had higher met-enkephalin immunoreactivity and secreted met-enkephalin levels, compared to control cells containing the expression vector only. In the formalin hindpaw-injection model, 15 days after subarachnoid transplant of cells, grafts of met-enkephalin and pro-enkephalin cells significantly reduced the number of formalin-evoked c-fos immunoreactive spinal neurons in the spinal cord, compared to grafts of vector-alone chromaffin cells. The use of such expandable cell lines, for chronic spinal delivery of opiates, could offer an attractive and safe alternative strategy based on ex vivo gene therapy for the control of opioid-sensitive chronic pain.
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PMID:Grafts of immortalized chromaffin cells bio-engineered to improve met-enkephalin release also reduce formalin-evoked c-fos expression in rat spinal cord. 1548 7

It has been shown that xenografts and allografts of spinally transplanted adrenal chromaffin cells produce antinociception in animals and pain relief in patients with cancer pain. As there is a very limited availability of human adrenal tissue to serve as allografts, the clinical need for xenogeneic chromaffin cells as transplants is obvious. Bovine adrenal glands as a steady source of chromaffin cells have been extensively studied. There is however concern about the possible infection in humans with retrovirus following transplantation. The purpose of this study is to use the pig as a preferred donor animal species for xenotransplantation into rat and monkey. As pigs have been cloned, this opens the door to gene-targeted technologies and allows for genetic modifications, which possibly could improve the efficacy and safety of chromaffin cell transplantation. Porcine chromaffin cells were isolated from adrenal glands of 6-8-month-old pigs. After culturing cells for 1 week in a medium containing serum, the release of met-enkephalin and norepinephrine from the cells was detected by high-performance liquid chromatography and radioimmunoassay with nicotine stimulation, lasting approximately 3 weeks. Transplantation of these cells into the subarachnoid space of rats produced antinociceptive effects on Adelta and C fiber-mediated responses lasting 2-3 weeks. Similar findings were observed in studies with macaque monkeys. Compared with the same number of bovine chromaffin cells, porcine chromaffin cells showed a more robust and longer antinociceptive effect, and could be a better source of cells for human transplantation.
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PMID:Porcine chromaffin cells, culture, and transplant for antinociceptive effects in rodents and primates. 1549 7

Cancer pain impairs the quality of life of cancer patients, but opioid analgesics can not only cause inhibition of respiratory function, and constipation, but also other significant side effects such as addiction and tolerance that further decrease quality of life. Thus, in the present study, the effects of electro-acupuncture treatment (EA) on mechanical allodynia were examined in cancer pain mouse model. In order to induce neuropathic cancer pain model, S-180 sarcoma cells were inoculated around the sciatic nerve of left legs of Balb/c mice. The mass of S-180 cancer cells embedded around sciatic nerve in a time course was confirmed by Magnetic Resonance Imaging (MRI) scanning. Mechanical allodynia was most consistently induced in mouse sarcoma cell line S-180 (2 x 10(6) sarcoma cells) treated group among all groups. EA stimulation (2Hz) was daily given to ST36 (Zusanli) of S-180 bearing mice for 30 min for 9 days after S-180 inoculation. EA treatment significantly prolonged paw withdrawal latency from 5 days after inoculation as well as shortened cumulative lifting duration from 7 days after inoculation compared with tumor control. In addition, the overexpressions of pain peptide substance P in dorsal horn of spinal cord were significantly decreased in EA treated group compared with tumor control on Day 9 after inoculation. Furthermore, EA treatment effectively increased the concentration of beta endorphin in blood and brain of mice more than tumor control as well as normal group. The concentration of beta-endorphin for EA treatment group increased by 51.457% in blood 12.6% in brain respectively, compared with tumor control group. These findings suggest that S-180 cancer pain model can be a consistent and short time animal model and also EA treatment can be an alternative therapeutic method for cancer pain via decreased substance P and increased beta endorphin.
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PMID:Substance P and beta endorphin mediate electroacupuncture induced analgesic activity in mouse cancer pain model. 1971 73

Endothelin-1 (ET-1) produced by various cancers is known to be responsible for inducing pain. While ET-1 binding to ETAR on peripheral nerves clearly mediates nociception, effects from binding to ETBR are less clear. The present study assessed the effects of ETBR activation and the role of endogenous opioid analgesia in carcinoma pain using an orthotopic cancer pain mouse model. mRNA expression analysis showed that ET-1 was nearly doubled while ETBR was significantly down-regulated in a human oral SCC cell line compared to normal oral keratinocytes (NOK). Squamous cell carcinoma (SCC) cell culture treated with an ETBR agonist (10(-4)M, 10(-5)M, and 10(-6) M BQ-3020) significantly increased the production of beta-endorphin without any effects on leu-enkephalin or dynorphin. Cancer inoculated in the hind paw of athymic mice with SCC induced significant pain, as indicated by reduction of paw withdrawal thresholds in response to mechanical stimulation, compared to sham-injected and NOK-injected groups. Intratumor administration of 3mg/kg BQ-3020 attenuated cancer pain by approximately 50% up to 3h post-injection compared to PBS-vehicle and contralateral injection, while intratumor ETBR antagonist BQ-788 treatment (100 and 300microg/kg and 3mg/kg) had no effects. Local naloxone methiodide (500microg/kg) or selective mu-opioid receptor antagonist (CTOP, 500microg/kg) injection reversed ETBR agonist-induced antinociception in cancer animals. We propose that these results demonstrate that peripheral ETBR agonism attenuates carcinoma pain by modulating beta-endorphins released from the SCC to act on peripheral opioid receptors found in the cancer microenvironment.
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PMID:Peripheral endothelin B receptor agonist-induced antinociception involves endogenous opioids in mice. 2020 45


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