Roles of 5-Hydroxytryptamine (5-HT) Receptor Subtypes in the Inhibitory Effects of 5-HT on C-Fiber Responses of Spinal Wide Dynamic Range Neurons in Rats

Abstract

5-Hydroxytryptamine (5-HT; serotonin) plays an important role in the descending control of nociception. 5-HT and its receptors have been extensively studied in the modulation of nociceptive transmission at the spinal level using behavioral tests that may be affected by the effects of 5-HT on motor performance and skin temperature. Using electrophysiological methods, the present study aimed to systematically investigate the roles of 5-HT receptor subtypes on the inhibitory effects of 5-HT on responses of the spinal wide dynamic range (WDR) neurons to C-fiber inputs in rats. Under basal conditions, topical application of 5-HT to the spinal cord inhibited the C-fiber responses of WDR neurons dose-dependently, whereas antagonists of 5-HT 1A [WAY 100635 [N-[2-[4-(2- The dorsal horn of the spinal cord is critical for nociceptive transmission. Nociceptive information impinging upon the dorsal horn from the skin, viscera, and other tissues is subjected to segmental, extrasegmental, and descending inhibitory controls (Melzack and Wall, 1965). It has been established that the descending control system from the brain exerts an inhibitory influence upon the spinal processing of nociceptive information. 5-Hydroxytryptamine (5-HT; serotonin) is a major neurotransmitter in the descending control system. In the spinal cord, at least four subtypes of 5-HT receptors (5-HT 1 -5-HT 4 ) have been identified, which are involved in spinal pain modulation. However, the roles of some of these receptor subtypes are not well defined, and previous

Motor activity induces release of serotonin in the dorsal horn of the rat lumbar spinal cord

“…Histological analysis showed the accuracy of microdialysis probe placements, the reaction of host tissue, and 5-HT fibers surrounding the probe Transverse sections of spinal cord at the level of the dialysing part of microdialysis probes (1mm) confirmed that probes were successfully inserted in the L4 segment of the dorsal horn (layers II, III, IV, V of Rexed [10,11]), ( Fig.1;Fig. 2-A).…”

“…Animals were placed in a spinal stereotactic aparatus (David Kopf Instruments, USA). A microdialysis probe (membrane diameter of 240μm, cut off of 6000 Daltons, CMA11/1 mm, CMA/Microdialysis, Sweden) was stereotactically inserted into the L4 dorsal horn segment of the spinal cord (vertebral body T13) [6] in layers II, III, IV, V of Rexed [10,11]. As proprioceptive areas are located within laminae III, IV, V the specific placement of the membrane of the probe allowed for sampling from proprioceptive areas within the dorsal horn.…”

Autofluorescent Flavoprotein Imaging of Spinal Nociceptive Activity

“…1; supplemental Videos 1, 2, available at www.jneurosci.org as supplemental material). This stimulus intensity is approximately three times C-fiber threshold, which has been shown to approximate 1 mA in rats in vivo (Rygh et al, 2000;Liu et al, 2007), thus exciting the majority of A␦-and C-fibers. The pattern of activity that we observed is similar to AFI responses elsewhere in the nervous system (Murakami et al, 2004;Reinert et al, 2004;Gao et al, 2006).…”

“…Electrical stimulus intensities ranging from one to more than three times C-fiber threshold were applied in our study (Rygh et al, 2000;Liu et al, 2007). Additionally, we used innocuous palpation causing mainly A␤-fiber stimulation in naive animals.…”

Electrophysiological properties of spinal wide dynamic range neurons in neuropathic pain rats following spinal nerve ligation

“…Only rats with significant mechanical allodynia, whose 50% PWT in ipsilateral hind limb was lower than 4.0 g, were selected for further electrophysiological studies. min), end-expiratory CO 2 (3.5%-4.5%), and rectal temperature (36.5-37.5 °C), and maintained within these ranges [20,21] . During electrode advancement, electrical pulses (0.5 Hz, 0.3-ms pulse width, 0.4 mA) were applied to the ipsilateral sciatic nerve as search stimuli so that a neuron with no spontaneous firing could be identified.…”