Over-expression of endothelin-1 in astrocytes, but not endothelial cells, ameliorates inflammatory pain response after formalin injection.

Abstract

AIMS:

Endothelin-1 (ET-1) has been suggested to be involved in different types of pain due to its neuromodulatory nature. However, its role in inflammatory pain processing, specifically the origin-specific effect, has not yet been clearly defined. Therefore, the aim of this study is to determine the role of cell-type specific ET-1 induction in the modulation of inflammatory pain processing.

MAIN METHODS:

The current study assesses the effects of ET-1 over-expression specifically targeted to astrocytes (GET-1) or endothelial cells (TET-1) on the expression of pain-like behaviors induced by a model of inflammatory pain, consisting of a formalin injection into the hind paw.

KEY FINDINGS:

The baseline sensitivity thresholds of GET-1 and TET-1 mice to the response elicited by tactile and radiant heat stimulation were similar to those observed in age-matched non-transgenic (NTg) controls. Relative to the NTg controls, GET-1 mice displayed a marked decrease in pain-like behavioral responses during the second phase of formalin-induced pain (i.e., 15-20 min after injection), whereas the responses elicited in TET-1 mice were unaltered. The levels of mRNA encoding adrenomedullin, calcitonin gene-related peptide and calcitonin-like receptor were elevated in the spinal cord of saline-injected GET-1 mice compared to those of NTg mice.

SIGNIFICANCE:

The current results support a suppressor role for astrocyte-derived ET-1 in inflammatory pain and suggest that the study of GET-1 mice might provide mechanistic insights for improving the treatment of inflammatory pain.

• Authors: Victor K L Hung, Samantha M Y Chen, Lydia W Tai, Ann Y S Chen, Sookja K Chung, C W Cheung
• Journal: Life sciences (Life Sci) Vol. 91 Issue 13-14 Pg. 618-22 (Oct 15 2012) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 22820168 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Calcitonin Receptor-Like Protein
• Calcrl protein, mouse
• Endothelin-1
• RNA, Messenger
• Adrenomedullin
• Formaldehyde
• Calcitonin Gene-Related Peptide

Topics

• Adrenomedullin (genetics)
• Animals
• Astrocytes (metabolism)
• Behavior, Animal
• Calcitonin Gene-Related Peptide (genetics)
• Calcitonin Receptor-Like Protein (genetics)
• Disease Models, Animal
• Endothelial Cells (metabolism)
• Endothelin-1 (genetics, metabolism)
• Formaldehyde (toxicity)
• Gene Expression Regulation
• Inflammation (physiopathology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Pain (physiopathology)
• RNA, Messenger (metabolism)
• Spinal Cord (metabolism)