Genetic Reduction of Chronic Muscle Pain in Mice Lacking Calcium/Calmodulin-Stimulated Adenylyl Cyclases

Kunjumon I Vadakkan; Hansen Wang; Shanelle W Ko; Evelyn Zastepa; Michele J Petrovic; Kathleen A Sluka; Min Zhuo

doi:10.1186/1744-8069-2-7

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Genetic Reduction of Chronic Muscle Pain in Mice Lacking Calcium/Calmodulin-Stimulated Adenylyl Cyclases

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Genetic Reduction of Chronic Muscle Pain in Mice Lacking Calcium/Calmodulin-Stimulated Adenylyl Cyclases

Kunjumon I Vadakkan, Hansen Wang, Shanelle W Ko, Evelyn Zastepa, Michele J Petrovic, Kathleen A Sluka and Min Zhuo

Molecular pain, Vol.2(1), pp.7-7

02/17/2006

DOI: 10.1186/1744-8069-2-7

PMCID: PMC1395303

PMID: 16503978

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Abstract

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.

Details

Title: Subtitle: Genetic Reduction of Chronic Muscle Pain in Mice Lacking Calcium/Calmodulin-Stimulated Adenylyl Cyclases
Creators: Kunjumon I Vadakkan - Graduate Program in Physical Therapy and Rehabilitation Sciences, University of Iowa, Iowa, IA, USA
Hansen Wang - Graduate Program in Physical Therapy and Rehabilitation Sciences, University of Iowa, Iowa, IA, USA
Shanelle W Ko - Graduate Program in Physical Therapy and Rehabilitation Sciences, University of Iowa, Iowa, IA, USA
Evelyn Zastepa - Graduate Program in Physical Therapy and Rehabilitation Sciences, University of Iowa, Iowa, IA, USA
Michele J Petrovic - Graduate Program in Physical Therapy and Rehabilitation Sciences, University of Iowa, Iowa, IA, USA
Kathleen A Sluka - Graduate Program in Physical Therapy and Rehabilitation Sciences, University of Iowa, Iowa, IA, USA
Min Zhuo - Graduate Program in Physical Therapy and Rehabilitation Sciences, University of Iowa, Iowa, IA, USA
Resource Type: Journal article
Publication Details: Molecular pain, Vol.2(1), pp.7-7
Publisher: SAGE Publications; Los Angeles, CA
DOI: 10.1186/1744-8069-2-7
PMID: 16503978
PMCID: PMC1395303
ISSN: 1744-8069
eISSN: 1744-8069
Language: English
Date published: 02/17/2006
Academic Unit: Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
Record Identifier: 9984040363202771

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