title: Effects of bupivacaine and tetrodotoxin on carrageenan-induced hind paw inflammation in rats (Part 2): cytokines and p38 mitogen-activated protein kinases in dorsal root ganglia and spinal cord.
abstract: BACKGROUND
  The authors previously showed that bupivacaine and tetrodotoxin via contralateral or ipsilateral sciatic block, but not systemically, attenuate local edema and hyperalgesia induced by carrageenan hind paw injection in rats. Bupivacaine, by all three routes, suppressed systemic cytokine activation, whereas tetrodotoxin was ineffective by all three routes. In the current study, the authors examined cytokine and p38 mitogen-activated protein kinase (MAPK) activation in lumbar dorsal root ganglia (DRGs) and spinal cord after carrageenan paw injections and sciatic blocks with either bupivacaine or tetrodotoxin.
  
  
  METHODS
  Ten groups of rats (n = 3-5) received injections in the following sites: right or left hind paw or right forepaw (carrageenan or saline) and left sciatic block (with epinephrine plus bupivacaine, tetrodotoxin, or saline; repeated 6 h later). Fifteen hours later, tumor necrosis factor alpha, interleukin 1beta, p38 MAPK, and phosphorylated p38 MAPK were measured by enzyme-linked immunosorbent assay in DRGs and in the spinal cord.
  
  
  RESULTS
  Carrageenan-induced hind paw inflammation enhanced tumor necrosis factor-alpha and interleukin-1beta production in bilateral DRGs and spinal cord and enhanced p38 MAPK activation in bilateral DRGs. These pathways were not activated after forepaw injection of carrageenan, suggesting a segmental mechanism. Neither bupivacaine nor tetrodotoxin inhibited cytokine and p38 MAPK activation after carrageenan injection.
  
  
  CONCLUSIONS
  Ipsilateral or contralateral sciatic blockade using either bupivacaine or tetrodotoxin does not inhibit carrageenan-induced activation of cytokines and p-38 MAPK in spinal cord and DRGs. Possible explanations may include incomplete degrees of conduction blockade or afferent signaling via saphenous nerves.
authors.affiliation: Department of Anesthesiology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Hélène
authors.initials: H
authors.lastname: Beloeil
authors.forename: Ru-Rong
authors.initials: RR
authors.lastname: Ji
authors.forename: Charles B
authors.initials: CB
authors.lastname: Berde
mesh_terms: D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage*; D002351:Carrageenan / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism*; D004359:Drug Therapy, Combination; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006614:Hindlimb / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013779:Tetrodotoxin / Q000008:administration & dosage*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016207:Cytokines; D013779:Tetrodotoxin; D002351:Carrageenan; D048051:p38 Mitogen-Activated Protein Kinases; D002045:Bupivacaine