Developing analgesics by enhancing spinal inhibition after injury: GABAA receptor subtypes as novel targets.

Abstract:

:The use of genetically-engineered mice has identified alpha2- and alpha3-subunit containing GABA(A) receptors as principal contributors to the spinal disinhibition that occurs after inflammation and neuropathic injury. Pharmacological comparison of subtype selective allosteric modulators such as NS11394 and L838417 with either non-selective or full GABA(A) receptor modulators indicates that in addition to involvement of specific subunits per se, the level of efficacy at individual alpha subunits appears to be a critical determinant of analgesic activity. Combined, these complementary approaches identify the restoration of spinal inhibition after inflammatory, and especially neuropathic injury (the primary focus of this article), as a possible unifying mechanism for providing analgesia in patients with chronic pain.

journal_name

Trends Pharmacol Sci

authors

Munro G,Ahring PK,Mirza NR

doi

10.1016/j.tips.2009.06.004

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

453-9

issue

9

eissn

0165-6147

issn

1873-3735

pii

S0165-6147(09)00123-0

journal_volume

30

pub_type

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