| |
| 50th Annual Meeting of the American Headache Society |
Boston, Massachusetts June 26-29, 2008 |
|
|
|
|
|
 |
Glial Cells and Pain Control |
 |
|
BY MAURY M. BREECHER
Contributing Writer |
BOSTON — Glial cells may not only dysregulate
pain but they also may dysregulate the actions of
opioids as well. In addition, there are now hints that
glial cells may be involved in the transition from acute
to chronic pain, reported Dr. Linda R. Watkins at the
50th Annual Scientific Meeting of the American Headache
Society on June 26.
“An intriguing glial activation receptor may potentially
lie at the heart of this…and we know how to block it,”
said Dr. Watkins of the University of Colorado at
Boulder.
“This is a highly speculative talk,” she cautioned.
“Issues of acute to chronic pain are very new to glial
research.”
Research accomplished over the last 15 years has clearly
documented that glial cells are importantly involved in
both the creation and maintenance of pathological pain
states such as neuropathic pain. Even more recent
research has shown that glial cells also regulate the
actions of opioids.
Even newer work reveals that prior activation of glial
cells can radically change how those cells behave. After
activation, those cells reach a primed state and when
re-activated, they over-respond to stimuli like aging,
stress, inflammation, trauma and opioids.
“This priming effect may have something to do with the
transition from acute to chronic pain,” Dr. Watkins
observed.
What do aging, stress, trauma, opioids and inflammation
have in common, she asked?
They all are involved with up-regulation of toll-like
receptor-4 (TLR4).
“This is a receptor you can think of as a ‘not me, not
right, not OK’ receptor,” noted Dr. Watkins. “It is a
receptor that recognizes bad things like bacteria by
binding to and being activated by things like bacteria
lipopolysacchaerides (LPS).”
Researchers have discovered that these receptors are
also activated “by every clinically relevant class of
opioid.”
Researchers have developed a “Two-Hit” Hypothesis that
after aging, stress, trauma/inflammation or opioid
exposure, a second “hit”—say activation of TLR4 by
infection—can create a “faster, stronger, longer
response by glial” —the brain cells produce much more
interleukin-1 or other inflammatory cytokines than do
brain cells of non-stressed controls.
The effect lasts longer too.
Experiments with rats supports the “two hit” hypothesis.
In response to a laparotomy, there is upregulation of
the expression of glial activation markers within the
spinal cord compared to control animals, but if the
animals have had surgery two weeks prior there is a
greater increase in pain.
“The identical event has been changed from no pain to
pain by prior surgery,” observed Dr. Watkins. “
If no pain can turn into pain, what would happen to an
animal in transient pain?
To test this, the researchers gave a sterile bladder
inflammation to a series of rats. What this does is
create referred pain down the hind paws of the animals
which progressively develops over time and then slowly
dissipates.
“If you gave the identical bladder inflammation but
proceeded it with a laparotomy two weeks earlier, you
see a much more rapid development of pain enhancement,
which shows no sign of receding even through the 3-month
experimental time period,” said Dr. Watkins. In other
words transient pain has been turned into chronic pain.
Research has also revealed that glial activation opposes
the analgesic efficacy of both morphine and methadone
(Hutchinson et al. Brain Behav Immunity, 2008 in press).
While speculative, the data to date suggests the
following conclusions, according to Dr. Watkins.
Glial responses change dependent upon history and time
after prior activating event. “Primed” glial
over-responds to new challenges: faster, stronger, and
longer. “Primed” glia can change: “no pain” to “pain”
and “pain” to “enduring pain.” |
|
| Copyright 2008 Elsevier Custom Conference Coverage. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the copyright owner. No responsibility is assumed by the Publisher for any injury and/or damage to persons or property as a matter of products liability, through negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Because of rapid advances in the medical sciences, the Publisher recommends that independent verification of diagnoses and drug dosages should be made. Opinions expressed in this publication are those of the original authors and do not necessarily reflect those of the Publisher, the sponsor, or the editors. Elsevier assumes no liability for any material published herein. |
|
|
|
