Page 30 - 71_02

GEOFFREY BURNSTOCK AN. R. ACAD. NAC. FARM.

treatment. Combined antisense and RNAi-mediated treatment for

specific inhibition of the recombinant rat P2X3 receptor appears to
be promising for pain therapy. Cytotoxic targeting using IB4-saporin

conjugate of isolectin IB4-binding nociceptive sensory neurons

decreases the severity to noxious stimuli. Antagonism of P2X1 and
P2X3 receptors by phenol red has recently been reported and shown
to cause significant increase in pressure and volume threshold

required to initiate the micturition reflex in female urethra-

anaesthetised rats. Modulation of neurotransmission through P2X3
receptors in central and peripheral nervous systems may contribute

to the anaesthesia and analgesia produced by barbiturates.

Tetramethylpyrazine, a traditional Chinese medicine, used as an

analgesic for dysmenorrhoea, inhibited significantly the first phase

of nociceptive behaviour induced by 5% formation and attenuated

slightly the second phase in the rat hindpaw pain model. Interactions

between vanilloid and metabotropic P2Y receptors are also being

explored in terms of treatments for chronic pain and thermal

hypersensitivity.

For neuropathic pain, the tactile allodynia that follows peripheral
nerve injury is reduced by A-134974, a novel adenosine kinase
inhibitor acting at spinal sites. Endogenous ATP acting on P2X
receptors appears to be necessary for the induction of the
postoperative pain characterised by mechanical allodynia.
Upregulation of P2Y1 receptor expression in DRG occurs after
transection of sciatic nerves. P2X4 receptors are induced in spinal
microglia that appear to gate tactile allodynia after nerve injury (26).
Intraspinal administration of p38 inhibitor suppressed allodynia,
which suggests that neuropathic pain hypersensitivity depends on
the activation of p38 signalling pattern in microglia in the dorsal
horn following peripheral nerve injury. Suramin inhibits spinal cord
microglia activation and long-term hyperalgesia induced by formalin
injection. Analgesic effects of intrathecal administration of P2Y
receptor agonists UTP and UDP in normal and the neuropathic pain
rat model have been reported suggesting that P2Y2 (and P2Y4) and
P2Y6 receptors, in contrast to P2X receptors, produce inhibitory
effects in spinal pain transmission. Purinergic mechanisms are also
beginning to be explored in relation to cancer pain.

310