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

Single unit extracellular recordings from the dorsal horn neurons were obta ined with glass micropipettes in pentobarbital-anesthetized rats. A total o f 115 wide dynamic range (WDR) neurons were studied in 94 rats. In normal r ats, the size of nociceptive receptive fields (RFs) of WDR neurons was appr oximately 123.3 +/- 8.21 mm(2) (n = 88). Following carrageenan-induced infl ammation. 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 carrage enan-injected rats (11.3 +/- 2.1 imp/s, n = 27) was greater than that in no rmal rats (7.1 +/- 0.8 imp/s, n = 88. P < 0.05). In 82% of WDR neurons in n ormal rats. there was a separation between the A- and C-responses. In contr ast, in 67% of the neurons in carrageenan-injected rats, the response to su prathreshold electrical stimuli was a long train with no separation between the A- and C-responses. In carrageenan-injected rats, the magnitude and du ration of the nociceptive responses were significantly increased compared t o those in normal rats, and the average C-response threshold (7.7 +/- 1.1 m A, 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-HT1A) recep tor agonist 8-hydroxy-DPAT hydroxybromide (8-OH-DPAT) (0.305, 1.525, 3.05, and 15.25 mM) dose-dependently increased A<delta>- and C-responses and post -discharge in most of the WDR neurons. Following carrageenan-induced inflam mation, the 8-OH-DPAT-induced facilitatory effect on A delta- and C-respons es and post-discharge was significantly enhanced (P < 0.05). Intrathecal in jection of the 5-hydroxytryptamine(1B) (5-HT1B) receptor agonist CGS12066A (0.222, 1.11, 2.22, and 11.1 mM) dose-dependently enhanced the C-response a nd post-discharge without influencing the A<delta>-response. In carrageenan -injected rats. CGS12066A not only enhanced the facilitatory effect on the C-response and post-discharge, but also facilitated the A delta -response. Intrathecal injection of the 5-HT1A receptor antagonist NAN-190 (0.2 mM) al one did not influence A delta- and C-responses and post-discharge of WDR ne urons 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 A delta- and C-responses and post-discharge was completely antagonized, whereas CGS12066A-induced f acilitation on the C-response and post-discharge was not influenced by co-a dministration of 0.2 mM NAN-190 and CGS12066A. These data suggest that 5-HT 1A and 5-HT1B receptor subtypes mediate the facilitatory effect of 5-HT on nociceptive processing in the spinal cord of rats. The excitability of dors al horn WDR neurons and the sensitivity of the neurons to intrathecal 5-HT1 A and 5-HT1B receptor agonists might increase following carrageenan-induced inflammation. (C) 2001 International Association for the Study of Pain. Pu blished by Elsevier Science B.V. All rights reserved.