Journal
TRENDS IN PHARMACOLOGICAL SCIENCES
Volume 30, Issue 11, Pages 581-591Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tips.2009.08.002
Keywords
-
Categories
Funding
- American Australian Association Merck Company Foundation Fellowship
- National Health and Medical Research Council CJ Martin Fellowship [ID 465423]
- NIH [DA015642, DA017670, DA024044, DE017782]
- National Institute on Drug Abuse
- National Institute on Alcohol Abuse and Alcoholism
Ask authors/readers for more resources
Glial activation participates in the mediation of pain including neuropathic pain, due to release of neuroexcitatory, proinflammatory products. Glial activation is now known to occur in response to opioids as well. Opioid-induced glial activation opposes opioid analgesia and enhances opioid tolerance, dependence, reward and respiratory depression. Such effects can occur, not via classical opioid receptors, but rather via non-stereoselective activation of toll-like receptor 4 (TLR4), a recently recognized key glial receptor participating in neuropathic pain as well. This discovery identifies a means for separating the beneficial actions of opioids (opioid receptor mediated) from the unwanted side-effects (TLR4/glial mediated) by pharmacologically targeting TLR4. Such a drug should be a stand-alone therapeutic for treating neuropathic pain as well. Excitingly, with newly-established clinical trials of two glial modulators for treating neuropathic pain and improving the utility of opioids, translation from rats-to-humans now begins with the promise of improved clinical pain control.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available