title: Suppression of adrenal gland-derived epinephrine enhances the corticosterone-induced antinociceptive effect in the mouse formalin test.
abstract: BACKGROUND
  There is both clinical and experimental evidence to support the application of corticosterone in the management of inflammation and pain. Corticosterone has been used to treat painful inflammatory diseases and can produce antinociceptive effects. Epinephrine is synthesized from norepinephrine by the enzyme phenylethanolamine N-methyltransferase (PNMT) and works as an endogenous adrenoceptor ligand secreted peripherally by the adrenal medulla. It is currently unclear whether corticosterone's antinociceptive effect is associated with the modulation of peripheral epinephrine.
  
  
  METHODS
  We first determined whether exogenous corticosterone treatment actually produced an antinociceptive effect in a formalin-induced pain model, and then examined whether this corticosterone-induced antinociceptive effect was altered by suppression of adrenal-derived epinephrine, using the following three suppression methods: (1) inhibition of the PNMT enzyme; (2) blocking peripheral epinephrine receptors; and (3) adrenalectomy.
  
  
  RESULTS
  Exogenous treatment with corticosterone at a high dose (50 mg/kg), but not at lower doses (5, 25 mg/kg), significantly reduced pain responses in the late phase. Moreover, injection of 2,3-dichloro-a-methylbenzylamine, a PNMT enzyme inhibitor, (10 mg/kg) before corticosterone treatment caused a leftward shift in the dose-response curve for corticosterone and injection of propranolol (5 mg/kg), but not phentolamine, also shifted the dose-response curve to the left during the late phase. Chemical sympathectomy with 6-hydroxydopamine had no effect on corticosterone-induced antinociceptive effect, but injection of a low dose of corticosterone produced an antinociceptive effect in adrenalectomized animals.
  
  
  CONCLUSIONS
  These results demonstrate that suppression of epinephrine, derived from adrenal gland, enhances the antinociceptive effect of exogenous corticosterone treatment in an inflammatory pain model.
authors.affiliation: Acupuncture, Moxibustion & Meridian Research Group, Medical Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Kang
authors.forename: D H
authors.initials: DH
authors.lastname: Roh
authors.forename: H W
authors.initials: HW
authors.lastname: Kim
authors.forename: H J
authors.initials: HJ
authors.lastname: Han
authors.forename: A J
authors.initials: AJ
authors.lastname: Beitz
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism* / Q000601:surgery; D000315:Adrenalectomy; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003345:Corticosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010147:Pain Measurement / Q000187:drug effects* / Q000523:psychology; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors; D011941:Receptors, Adrenergic / Q000187:drug effects; D013563:Sympathectomy, Chemical
chemical_list: D000893:Anti-Inflammatory Agents; D011941:Receptors, Adrenergic; D010625:Phenylethanolamine N-Methyltransferase; D003345:Corticosterone; D004837:Epinephrine