title: Second messengers mediating the expression of neuroplasticity in a model of chronic pain in the rat.
abstract: Hyperalgesic priming is a model of the transition from acute to chronic pain, in which previous activation of cell surface receptors or direct activation of protein kinase C epsilon markedly prolongs mechanical hyperalgesia induced by pronociceptive cytokines. We recently demonstrated a role of peripheral protein translation, alpha-calmodulin-dependent protein kinase II (αCaMKII) activation, and the ryanodine receptor in the induction of hyperalgesic priming. In the present study, we tested if they also mediate the prolonged phase of prostaglandin E2-induced hyperalgesia. We found that inhibition of αCaMKII and local protein translation eliminates the prolonged phase of prostaglandin E2 hyperalgesia. Although priming induced by receptor agonists or direct activation of protein kinase C epsilon occurs in male but not female rats, activation of αCaMKII and the ryanodine receptor also produces priming in females. As in males, the prolonged phase of prostaglandin E2-induced hyperalgesia in female rats is also protein kinase C epsilon-, αCaMKII-, and protein translation-dependent. In addition, in both male and female primed rats, the prolonged prostaglandin E2-induced hyperalgesia was significantly attenuated by inhibition of MEK/ERK. On the basis of these data, we suggest that the mechanisms previously shown to be involved in the induction of the neuroplastic state of hyperalgesic priming also mediate the prolongation of hyperalgesia.
  
  
  CONCLUSIONS
  The data provided by this study suggest that direct intervention on specific targets may help to alleviate the expression of chronic hyperalgesic conditions.
authors.affiliation: Division of Neuroscience, Departments of Medicine and Oral Surgery, University of California at San Francisco, 521 Parnassus Avenue, San Francisco, California.
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Ferrari
authors.affiliation: Division of Neuroscience, Departments of Medicine and Oral Surgery, University of California at San Francisco, 521 Parnassus Avenue, San Francisco, California.
authors.forename: Oliver
authors.initials: O
authors.lastname: Bogen
authors.affiliation: Division of Neuroscience, Departments of Medicine and Oral Surgery, University of California at San Francisco, 521 Parnassus Avenue, San Francisco, California.. Electronic address: jon.levine@ucsf.edu.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism; D059350:Chronic Pain / Q000503:physiopathology*; D015232:Dinoprostone; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D014176:Protein Biosynthesis; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*; D012727:Sex Characteristics
chemical_list: D002135:Calcium-Binding Proteins; C581829:Camk2n1 protein, rat; D002352:Carrier Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D051744:Protein Kinase C-epsilon; D015232:Dinoprostone
keywords: Second messengers; hyperalgesic priming; mechanical hyperalgesia; rat; sensory neuron