Although previous reports have suggested that the sigma 1 (sigma(1)) receptor may be involved in
pain sensation, its specific site of action has not been elucidated. The aim of present study was to determine the role of the spinal sigma(1) receptor in
formalin-induced
pain behavior, spinal cord Fos expression and phosphorylation of
N-methyl-D-aspartate receptor subunit 1 (pNR1). Intrathecal (i.t.) pretreatment with the selective sigma(1) receptor antagonist,
BD-1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)
ethylamine dihydrobromide) (10-100 nmol) dose dependently reduced
formalin-induced
pain behaviors in second phase, but not first phase, of the
formalin test. I.t. injection of
BD-1047 also reduced
formalin-evoked Fos expression and pNR1 at the
protein kinase C-dependent site, serine-896 (Ser896) and the
protein kinase A-dependent site, serine-897 (Ser897) in spinal dorsal horn.i.t.
BMY-14802 ((alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol hydrochloride) (10-100 nmol, sigma(1) receptor antagonist and 5-HT(1A) receptor agonist) dose dependently reduced
formalin-induced
pain behaviors in both phases. However, the 5-HT(1A) receptor might not be involved in the antinociceptive effect of
BMY-14802 on the second phase, since i.t. pretreatment with the 5-HT(1A) receptor antagonist
propranolol ((S)-1-isopropylamino-3-(1-naphthyloxy)-
2-propanol hydrochloride) (injected 10 min prior to i.t.
BMY-14802) partially blocked the effect of
BMY-14802 on the first phase of the
formalin test but did not affect the inhibitory effect of
BMY-14802 on the second phase. In addition, i.t.
BMY-14802 significantly reduced
formalin-evoked Fos expression and pNR1 (Ser896 and Ser897) expression in spinal dorsal horn. The results of this study suggest that selective blockage of spinal sigma(1) receptors can reduce
pain behaviors, spinal cord Fos expression and pNR1 (Ser896 and Ser897) expression associated with the second phase of the
formalin test.