Faculty Collaboration Database

Phosphorylation of CREB and mechanical hyperalgesia is reversed by blockade of the cAMP pathway in a time-dependent manner after repeated intramuscular acid injections. J Neurosci 2003 Jul 02;23(13):5437-45

Date

07/05/2003

Pubmed ID

12843242

Pubmed Central ID

PMC6741249

DOI

10.1523/JNEUROSCI.23-13-05437.2003

Scopus ID

2-s2.0-0038384072 (requires institutional sign-in at Scopus site)   123 Citations

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.

Author List

Hoeger-Bement MK, Sluka KA

Author

Marie Hoeger Bement MPT,PhD Associate Professor in the Physical Therapy department at Marquette University

MESH terms used to index this publication - Major topics in bold

Acids
Adenine
Adenylyl Cyclase Inhibitors
Animals
Behavior, Animal
Chronic Disease
Cyclic AMP
Cyclic AMP Response Element-Binding Protein
Cyclic AMP-Dependent Protein Kinases
Disease Models, Animal
Dose-Response Relationship, Drug
Enzyme Inhibitors
Fibromyalgia
Hyperalgesia
Injections, Intramuscular
Injections, Spinal
Male
Motor Activity
Muscle, Skeletal
Pain Measurement
Phosphorylation
Rats
Rats, Sprague-Dawley
Signal Transduction
Spinal Cord