Buprenorphine Activates and Opioid Receptor Like-1 Receptors Simultaneously, but the Analgesic Effect Is Mainly Mediated by Receptor Activation in the Rat Formalin Test

ABSTRACT Buprenorphine is a mixed opioid receptor agonist-antagonist. Recently, buprenorphine was reported to act as an agonist to opioid receptor like-1 (ORL1) receptor. In the present study, we examined the role of spinal and supraspinal receptors and spinal and supraspinal ORL1 receptors in producing an analgesic effect by intrathecal (i.t.), intracerebroventricular (i.c.v.), or i.p. administration of buprenorphine in the rat formalin test. Male rats were prepared with i.t. catheters or i.c.v. injection cannulas. The paw formalin injection (50 l of 5% formalin) induces biphasic flinching (phase 1, 0 -6 min; phase 2, 10 -60 min) of the injected paw. Buprenorphine, naloxone (a -opioid Buprenorphine is a derivative of the morphine alkaloid thebaine and is used for the treatment of moderate to severe pain Recently, buprenorphine has been reported to act as an agonist at opioid receptor like-1 (ORL1) receptors (BlomsFunke et al., 2000). Moreover, buprenorphine did not produce an analgesic effect in 1 -opioid receptor-deficient mice -Opioid receptors and ORL1 receptors are widely located in the nervous system, and there are not enough data to determine which -opioid receptor plays an important role in producing an analgesic effect of buprenorphine and which ORL1 receptor plays an important role in suppressing an analgesic effect of buprenorphine when buprenorphine is administered systemically. Moreover, it is possible that the analgesic effect of systemically administered buprenorphine can be attributed to the activation of spinal ORL1 receptors. In the present study, we investigated the analgesic effect of intrathecal (i.t.), intracerebroventricular (i.c.v.), or i.p. ad