The role of 5-hydroxytryptamine 1A and 5-hydroxytryptamine 1B receptors in modulating spinal nociceptive transmission in normal and carrageenan-injected rats

Abstract

Single unit extracellular recordings from the dorsal horn neurons were obtained with glass micropipettes in pentobarbital-anesthetized rats. A total of 115 wide dynamic range (WDR) neurons were studied in 94 rats. In normal rats, the size of nociceptive receptive fields (RFs) of WDR neurons was approximately 123.3±8.21 mm 2 ( n=88). Following carrageenan-induced inflammation, the RFs were markedly enlarged (332.4±30.1 mm 2, n=27, P<0.001). The frequency of background activity of the WDR neurons in carrageenan-injected rats (11.3±2.1 imp/s, n=27) was greater than that in normal rats (7.1±0.8 imp/s, n=88, P<0.05). In 82% of WDR neurons in normal rats, there was a separation between the A- and C-responses. In contrast, in 67% of the neurons in carrageenan-injected rats, the response to suprathreshold electrical stimuli was a long train with no separation between the A- and C-responses. In carrageenan-injected rats, the magnitude and duration of the nociceptive responses were significantly increased compared to those in normal rats, and the average C-response threshold (7.7±1.1 mA, n=27) was lower than that in normal rats (10.4±0.7 mA, n=88, P<0.05). Intrathecal injection of the 5-hydroxytryptamine 1A (5-HT 1A) receptor agonist 8-hydroxy-DPAT hydroxybromide (8-OH-DPAT) (0.305, 1.525, 3.05, and 15.25 mM) dose-dependently increased Aδ- and C-responses and post-discharge in most of the WDR neurons. Following carrageenan-induced inflammation, the 8-OH-DPAT-induced facilitatory effect on Aδ- and C-responses and post-discharge was significantly enhanced ( P<0.05). Intrathecal injection of the 5-hydroxytryptamine 1B (5-HT 1B) receptor agonist CGS12066A (0.222, 1.11, 2.22, and 11.1 mM) dose-dependently enhanced the C-response and post-discharge without influencing the Aδ-response. In carrageenan-injected rats, CGS12066A not only enhanced the facilitatory effect on the C-response and post-discharge, but also facilitated the Aδ-response. Intrathecal injection of the 5-HT 1A receptor antagonist NAN-190 (0.2 mM) alone did not influence Aδ- and C-responses and post-discharge of WDR neurons in normal rats. When 0.2 mM NAN-190 was co-administered with 3.05 mM 8-OH-DPAT, the facilitatory effect of 8-OH-DPAT on Aδ- and C-responses and post-discharge was completely antagonized, whereas CGS12066A-induced facilitation on the C-response and post-discharge was not influenced by co-administration of 0.2 mM NAN-190 and CGS12066A. These data suggest that 5-HT 1A and 5-HT 1B receptor subtypes mediate the facilitatory effect of 5-HT on nociceptive processing in the spinal cord of rats. The excitability of dorsal horn WDR neurons and the sensitivity of the neurons to intrathecal 5-HT 1A and 5-HT 1B receptor agonists might increase following carrageenan-induced inflammation.