1. The aim of the present study is to characterize the role of spinal endogenous
ATP and P2X receptors in the generation of neurogenic and inflammatory
pain. We examined the effects of intrathecal treatment with P2X receptor antagonists on the
formalin- and
capsaicin-induced nociceptive behaviours in mice. 2. Intrathecal pretreatment with the general P2 receptor antagonist, pyridoxal-phosphate-6-azophenyl-2', 4'-disulphonic
acid (
PPADS), significantly suppressed both the first and second phases of the
formalin-induced nociceptive behaviour. The second phase of the nociceptive response was also suppressed by intrathecal treatment with
PPADS after the first phase. Furthermore, pretreatment with the selective antagonist for the P2X1, P2X3 and P2X2+3 receptors,
2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (
TNP-ATP), significantly reduced the first phase, but not the second phase. The second phase was also not suppressed by intrathecal
TNP-ATP after the first phase. 3.
Capsaicin-induced nociceptive behaviour that has been shown to be a model for neurogenic
pain, was also significantly suppressed by intrathecal pretreatment with
PPADS or
TNP-ATP. 4. Nociceptive behaviour in the first phase of the
formalin test and in the
capsaicin test were significantly inhibited by intrathecal pretreatment with
alpha, beta-methylene ATP (alpha,betameATP: 5 microg mouse-1) 15 min prior to injection of
formalin or
capsaicin. This treatment has been previously shown to desensitize spinal
P2X3 receptor subtypes in vivo. 5. These findings suggest that spinal endogenous
ATP may play a role in (1) the
formalin- and
capsaicin-induced neurogenic
pain via the
PPADS- and
TNP-ATP-sensitive P2X receptors which are also desensitized by alpha,betameATP (perhaps the
P2X3 receptor subtype) and (2)
formalin-induced inflammatory
pain via
PPADS-sensitive,
TNP-ATP- and alpha,betameATP-insensitive P2X (and/or P2Y) receptors.