Genetic reduction of chronic muscle pain in mice lacking calcium/calmodulin-stim

[Guest guest]

http://www.molecularpain.com/content/2/1/7/abstract

Genetic reduction of chronic muscle pain in mice lacking

calcium/calmodulin-stimulated adenylyl cyclases

Kunjumon I Vadakkan , Hansen Wang , Shanelle W Ko , Zastepa ,

Michele J Petrovic , Kathleen A Sluka and Min Zhuo

Molecular Pain 2006, 2:7 Published 17 February 2006

Background

The Ca2+/calmodulin-stimulated adenylyl cyclase (AC) isoforms AC1 and

AC8, couple NMDA receptor activation to cAMP signaling pathways in

neurons and are important for development, learning and memory, drug

addiction and persistent pain. AC1 and AC8 in the anterior cingulate

cortex (ACC) and the spinal cord were previously shown to be

important in subcutaneous inflammatory pain. Muscle pain is different

from cutaneous pain in its characteristics as well as conducting

fibers. Therefore, we conducted the present work to test the role of

AC1 and AC8 in both acute persistent and chronic muscle pain.

Results

Using an acute persistent inflammatory muscle pain model, we found

that the behavioral nociceptive responses of both the late phase of

acute muscle pain and the chronic muscle inflammatory pain were

significantly reduced in AC1 knockout (KO) and AC1 & 8 double knockout

(DKO) mice. Activation of other adenylyl cyclases in these KO mice by

microinjection of forskolin into the ACC or spinal cord, but not into

the peripheral tissue, rescued the behavioral nociceptive responses.

Additionally, intra-peritoneal injection of an AC1 inhibitor

significantly reduced behavioral responses in both acute persistent

and chronic muscle pain.

Conclusion

The results of the present study demonstrate that neuronal

Ca2+/calmodulin-stimulated adenylyl cyclases in the ACC and spinal

cord are important for both late acute persistent and chronic

inflammatory muscle pain.