Kawabata A, Kawao N, Kuroda R, Tanaka A, Itoh H, Nishikawa H
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Osaka, Japan.
Neuroreport. 2001 Mar 26;12(4):715-9. doi: 10.1097/00001756-200103260-00020.
Protease-activated receptor-2 (PAR-2), a member of the G protein-coupled, seven trans-membrane domain receptor family, is activated by trypsin/tryptase and present in various tissues including the primary sensory neurons, playing a role in development of neurogenic inflammation. The present study examined if activation of peripheral PAR-2 could modulate nociception in the rat. Expression of mRNA for PAR-2 was confirmed in the L4-6 dorsal root ganglia, but not spinal cord. The PAR-2-activating peptide SLIGRL-NH2 administered by the intraplantar (i.pl.) route, produced thermal, but not mechanical, hyperalgesia in the rat, although the PAR-2-inactive control peptide LSIGRL-NH2 had no effect. Not only the PAR-2-activating but also inactive peptides elicited nociceptive behavior (licking/biting) in the intact rats, whereas only the former peptide produced such behavior in the rats that had received repeated administration of compound 48/80 for mast cell depletion. These data provide novel evidence that activation of peripheral PAR-2 is pro-nociceptive, producing thermal hyperalgesia and also triggering pain sensation, by itself, independently of mast cell degranulation.
蛋白酶激活受体-2（PAR-2）是G蛋白偶联的七跨膜结构域受体家族的成员，可被胰蛋白酶/类胰蛋白酶激活，存在于包括初级感觉神经元在内的各种组织中，在神经源性炎症的发展中起作用。本研究检测了外周PAR-2的激活是否能调节大鼠的痛觉。在L4-6背根神经节中证实了PAR-2的mRNA表达，但脊髓中未检测到。通过足底内（i.pl.）途径给予PAR-2激活肽SLIGRL-NH2，可使大鼠产生热痛觉过敏，但不会引起机械性痛觉过敏，而PAR-2无活性的对照肽LSIGRL-NH2则无此作用。PAR-2激活肽和无活性肽均可在完整大鼠中引发伤害性行为（舔/咬），而只有前者能在接受过反复给予化合物48/80以耗尽肥大细胞的大鼠中引发此类行为。这些数据提供了新的证据，表明外周PAR-2的激活具有促痛作用，可产生热痛觉过敏，并能独立于肥大细胞脱颗粒而自身引发痛觉。
