Prostaglandins (PGs) are ubiquitously distributed in virtually all mammalian tissues and organs, and it has been well documented that PGs are involved in various aspects of inflammation including pain. Accumulating evidence indicates that PGs are critical for the processing of pain, not only in the periphery but also at the spinal level.
We showed that intrathecal (i.t.) administration of PGD
2 and PGE
2 induced hyperalgesia to noxious stimuli and that i.t. PGE
2 and PGF
2α induced allodynia, a state of discomfort and pain evoked by innocuous stimuli, in conscious mice. PGF
2α augmented the allodynia evoked by PGE
2 additively at submaximal doses. On the other hand, PGD
2 blocked the allodynia induced by PGE
2, but did not affect the PGF
2α-induced one, suggesting that the mechanisms of allodynia induced by PGE
2 and PGF
2α may be different.
Both glutamate and nitric oxide (NO) have recently been paid much attention because they are reported to be involved in long-term potentiation (LTP), a potential cellular mechanism for memory and learning. We demonstrated from pharmacological studies that PGE
2-and PGF
2α-induced allodynia are mediated by activation of glutamate receptors and following NO production, but in a defferent manner.
We have recently secceeded in purification and characterization of a novel heptadecapeptide called nociceptin in bovine brains as an endogenous ligand for ROR-C, an opioid receptor homologue cloned from rat cerebrum. Intrathecal administration of nociceptin induced allodynia by innocuous tactile stimuli and hyperalgesia by noxious thermal stimuli in conscious mice. PGD
2 blocked the allodynia induced by nociceptin, but did not affect the nociceptin-induced hyperal-gesia. Furthermore, the allodynia caused by nociceptin was dose-dependently blocked by glycine.
These results demonstrate that there exist at least two mechanisms for induction of allodynia: disinhibition through anti-glycinergic effect and hyperexcitability through a pathway that includes the glutamate receptor-NO-cGMP system in the mouse spinal cord. These results also imply that endogenous PGD
2 may play a modulatory role in the appearance of allodynia under physiological conditions. In a series of experiments, we demonstrated that PGs play central roles in pain transmission with interactions of other neurotransmitter systems, especially with the opioid system.
抄録全体を表示