This study evaluated the antinociceptive effects of the selective and non-
peptide CXCR2 antagonist
SB225002 in mouse models of
pain. As assessed in different tests of spontaneous nociception, intraperitoneal (i.p.) administration of
SB225002 caused consistent and dose-related reduction of
acetic acid-induced abdominal constrictions, whereas it did not significantly affect the nociception evoked by
formalin,
capsaicin,
glutamate or
phorbol ester acetate (PMA). Systemic treatment with
SB225002 strikingly reduced the spontaneous nociception induced by
8-bromo-cAMP (8-Br-cAMP), or mechanical hypernociception induced by
prostaglandin E(2) (
PGE(2)),
epinephrine, or the keratinocyte-derived
chemokine (KC). In the
carrageenan model,
SB225002 markedly reduced mechanical hypernociception when administered by i.p., intrathecal (i.t.) or intracerebroventricular (i.c.v.) routes, or even when co-administered with
carrageenan into the mouse paw, indicating peripheral and central sites of action for
SB225002. In addition, i.p. treatment with
SB225002 significantly attenuated the increase in MPO activity or the elevation of IL-1beta,
TNFalpha or KC levels following
carrageenan injection. In the persistent models of
pain evoked by complete
Freund's adjuvant (CFA) or by the partial
ligation of the sciatic nerve (PLSN), the repeated administration of
SB225002 displayed prominent and long-lasting antinociceptive effects. Notably,
SB225002 did not evoke unspecific central effects, as evaluated in the open-field and rota-rod tests, or even in the latency responses for thermal stimuli. Our data confirm the previous notion on the critical role exerted by
chemokines in
pain, indicating that selective CXCR2 antagonists, such as
SB225002, might well represent interesting and innovative alternatives for the management of both acute and
chronic pain.