Phosphorylation of CREB and mechanical hyperalgesia is reversed by blockade of the cAMP pathway in a time-dependent manner after repeated intramuscular acid injections

Marie K Hoeger-Bement; Kathleen A Sluka

doi:10.1523/JNEUROSCI.23-13-05437.2003

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Phosphorylation of CREB and mechanical hyperalgesia is reversed by blockade of the cAMP pathway in a time-dependent manner after repeated intramuscular acid injections

Journal article

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Phosphorylation of CREB and mechanical hyperalgesia is reversed by blockade of the cAMP pathway in a time-dependent manner after repeated intramuscular acid injections

Marie K Hoeger-Bement and Kathleen A Sluka

The Journal of neuroscience, Vol.23(13), pp.5437-5445

07/02/2003

DOI: 10.1523/JNEUROSCI.23-13-05437.2003

PMCID: PMC6741249

PMID: 12843242

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Abstract

Spinal activation of the cAMP pathway produces mechanical hyperalgesia, sensitizes nociceptive spinal neurons, and phosphorylates the transcription factor cAMP-responsive element binding protein (CREB), which initiates gene transcription. This study examined the role of the cAMP pathway in a model of chronic muscle pain by assessing associated behavioral changes and phosphorylation of CREB. Bilateral mechanical hyperalgesia of the paw was induced by administering two injections of acidic saline, 5 d apart, into the gastrocnemius muscle of male Sprague Dawley rats. Interestingly, the increases in immunoreactivity for CREB and phosphorylated CREB (p-CREB) in the spinal dorsal horn occur 24 hr, but not 1 week, after the second injection of acidic saline compared with pH 7.2 intramuscular injections. Spinal blockade of adenylate cyclase prevents the expected increase in p-CREB that occurs after intramuscular acid injection. The reversal of mechanical hyperalgesia by adenylate cyclase or protein kinase A inhibitors spinally follows a similar pattern with reversal at 24 hr, but not 1 week, compared with the vehicle controls. The p-CREB immunoreactivity in the superficial dorsal horn correlates with the mechanical withdrawal threshold such that increases in p-CREB are associated with decreases in threshold. Therefore, activation of the cAMP pathway in the spinal cord phosphorylates CREB and produces mechanical hyperalgesia associated with intramuscular acid injections. The mechanical hyperalgesia and phosphorylation of CREB depend on early activation of the cAMP pathway during the first 24 hr but are independent of the cAMP pathway by 1 week after intramuscular injection of acid.

Hyperalgesia - chemically induced

Phosphorylation

Motor Activity - drug effects

Male

Adenylyl Cyclase Inhibitors

Dose-Response Relationship, Drug

Enzyme Inhibitors - administration & dosage

Fibromyalgia - drug therapy

Muscle, Skeletal - drug effects

Behavior, Animal - drug effects

Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors

Cyclic AMP - metabolism

Disease Models, Animal

Cyclic AMP-Dependent Protein Kinases - metabolism

Injections, Spinal

Adenine - analogs & derivatives

Rats

Pain Measurement - drug effects

Injections, Intramuscular

Rats, Sprague-Dawley

Acids - administration & dosage

Adenine - administration & dosage

Hyperalgesia - physiopathology

Animals

Fibromyalgia - chemically induced

Hyperalgesia - drug therapy

Signal Transduction - drug effects

Muscle, Skeletal - physiopathology

Cyclic AMP Response Element-Binding Protein - metabolism

Spinal Cord - physiopathology

Fibromyalgia - physiopathology

Chronic Disease

Details

Title: Subtitle: Phosphorylation of CREB and mechanical hyperalgesia is reversed by blockade of the cAMP pathway in a time-dependent manner after repeated intramuscular acid injections
Creators: Marie K Hoeger-Bement - Graduate Program in Physical Therapy and Rehabilitation Science, Neuroscience Graduate Program, Pain Research Program, University of Iowa, Iowa City, Iowa 52242, USA
Kathleen A Sluka
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.23(13), pp.5437-5445
Publisher: United States
DOI: 10.1523/JNEUROSCI.23-13-05437.2003
PMID: 12843242
PMCID: PMC6741249
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: K02 AR 02201 / NIAMS NIH HHS R01 NS 39734 / NINDS NIH HHS F31 NS43962 / NINDS NIH HHS
Language: English
Date published: 07/02/2003
Academic Unit: Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
Record Identifier: 9984040473802771

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