1,3-Di-o-tolylguanidine (DTG) differentially affects acute and tonic formalin pain: antagonism by rimcazole

Pharmacol Biochem Behav. 1995 Sep;52(1):175-8. doi: 10.1016/0091-3057(95)00085-b.


The role of the sigma receptor in prolonged pain was examined by assessing the effects of 1,3,di-o-tolylguanidine (DTG), a selective sigma receptor ligand, on the formalin test in mice. Formalin injected subcutaneously into the hindpaw produces a biphasic pain response: an acute phase of short duration followed by a longer-lasting tonic phase. DTG (10 mg/kg, i.p.) potently reduced pain behavior in the acute phase but increased pain behavior in the tonic phase. Rimcazole (5 and 10 mg/kg, i.p.), a selective sigma receptor antagonist, blocked both the DTG-induced decrease and increase in pain behavior observed in the acute and tonic phases, respectively. These data support previous findings indicating a modulatory role for the sigma receptor in nociceptive processes, and suggest that this receptor differentially modulates acute vs. tonic pain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carbazoles / pharmacology*
  • Formaldehyde*
  • Guanidines / antagonists & inhibitors
  • Guanidines / pharmacology*
  • Male
  • Mice
  • Pain Measurement / drug effects*
  • Receptors, sigma / antagonists & inhibitors


  • Carbazoles
  • Guanidines
  • Receptors, sigma
  • Formaldehyde
  • rimcazole
  • 1,3-ditolylguanidine