IMR Press / FBL / Volume 10 / Issue 1 / DOI: 10.2741/1534

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Managing chronic pain with encapsulated cell implants releasing catecholamines and endogenous opiods
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1 Department of Surgery, Division of Plastic and Reconstructive Surgery, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA
2 Vice President of Research, LCT BioPharma, Inc., 766 Laten Knight Rd., Cranston, RI 02921

Academic Editor: Rhoda Maneckjee

Front. Biosci. (Landmark Ed) 2005, 10(1), 367–378; https://doi.org/10.2741/1534
Published: 1 January 2005
(This article belongs to the Special Issue New perspectives in the therapeutic use of opioids)
Abstract

Spinal injections (intrathecal) of norepinephrine and/or opiod agonists are antinociceptive and when administered together may act in synergy. Spinal implants of adrenal chromaffin cells are an effective method for sustained delivery of the analgesic substances norepinephrine and enkephalin to the central nervous system (CNS). One method of packaging and implanting cell-loaded devices into the intrathecal space of recipients is by encapsulating the cell suspensions in a polymer membrane prior to implantation. Cells/tissue packaged within an encapsulating membrane obviate the need for immunosuppressive therapies in transplant recipients. In addition, device output can be quantified prior to implantation, and following the removal of the spinal implant. The ability to retrieve the devices with the present tubular configuration also confers an additional margin of safety over unencapsulated chromaffin cell implants. This paper reviews the research and clinical observations of cellular transplants containing adrenal chromaffin cells for relieving chronic pain. Encapsulated cell technology is discussed with an emphasis on our experiences developing pain-modulating clinical devices. The human-sized prototype devices were loaded with enzymatically isolated bovine chromaffin cells and maintained in vitro for 7 - 8 days in serum-free media. Two days prior to implantation, each device was assayed by static incubation to measure catecholamine and met-enkephalin output, and qualified devices (n = 6) were implanted into the sheep subarachnoid space for 6 weeks. Following a 6 week in life period, the retrieval forces of prototype devices were measured during removal from the subarachnoid space. Static incubation of the devices immediately following retrieval and after a 24 hour re-incubation period were used to quantify norepinephrine and met-enkephalin secretion profiles. This study demonstrated the safety, retrievability and maintenance of pharmacologically active encapsulated chromaffin cell-loaded devices with human implant dimensions.

Keywords
Chronic pain
Analgesia
Cellular encapsulation
Immunoisolation
Norepinephrine
Met-enkephalin
Review
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