Biomedical subjects

Min Zhuo

Publications and source records attributed to Min Zhuo.

60 records · Page 4Linked to original sources

PubMed2002

Facilitation and attenuation of a visceral nociceptive reflex from the rostroventral medulla in the rat.

BACKGROUND & AIMS: Noxious inputs from somatic tissue are subject to biphasic descending modulation from the rostroventral medulla (RVM). In the present study, we investigated descending facilitatory and inhibitory influences from the RVM on a visceral nociceptive reflex. METHODS: The visceromotor response (VMR), a contraction of peritoneal musculature during noxious colorectal distention (80 mm Hg, 20 seconds), was quantified as the integrated electromyogram. RESULTS: At 22 sites in the RVM, electrical stimulation produced biphasic effects, facilitating the VMR at low (5, 10, and 25 microA) and inhibiting it at greater (>50 microA) intensities of stimulation. Electrical stimulation at all intensities tested (5-200 microA) in other sites in the RVM only inhibited (30 sites) or only facilitated (12 sites) the VMR to colorectal distention. Activation of glutamatergic receptors in the RVM replicated the effects of electrical stimulation. Reversible blockage (intraspinal lidocaine injection) or irreversible transection of spinal funiculi revealed that descending facilitatory influences from the RVM were conveyed in the ventrolateral/ventral funiculus, whereas descending inhibitory influences were contained in the dorsolateral funiculi. CONCLUSIONS: Spinal visceral nociceptive reflexes are subject to facilitatory modulation from the RVM, providing the basis for a mechanism by which visceral sensations can be enhanced from supraspinal sites.

Animals↗

PubMed2002

Long-lasting changes in rostral ventral medulla neuronal activity after inflammation.

Activity-dependent synaptic plasticity occurs in many regions of the central nervous system. It is known that spinal sensory transmission undergoes long-lasting changes after tissue injury and inflammation, but much less is known about descending modulation. In the present study, we demonstrate that tissue injury causes long-lasting changes within the rostral ventral medulla, a region critical for descending modulation of spinal sensory transmission. Subcutaneous formalin injections induced changes in the activity of rostral ventral medulla neurons, particularly during phase 2 (10 to 55 minutes after injection). The activity of neutral cells, which showed no response to acute noxious stimuli, was significantly decreased after formalin injection. Furthermore, 2 "silent" cells became active after the formalin injection. To demonstrate directly that descending biphasic modulation from the rostral ventral medulla was affected after the inflammation, we investigated descending modulation of a spinal nociceptive reflex produced by focal electrical stimulation in the rostral ventral medulla and found that both facilitation and inhibition were significantly decreased. These data suggest that rostral ventral medulla circuits modulating spinal sensory transmission undergo profound and long-lasting changes after tissue injury and inflammation. This may contribute to the pathological modification of nociceptive processing in chronic pain states.

Journal Article↗

PubMed2002

Synergistic enhancement of glutamate-mediated responses by serotonin and forskolin in adult mouse spinal dorsal horn neurons.

Glutamate is the major excitatory amino acid neurotransmitter in the CNS, including the neocortex, hippocampus, and spinal cord. Normal synaptic transmission is mainly mediated by glutamate AMPA and/or kainate receptors. Glutamate N-methyl-D-aspartate (NMDA) receptors are normally inactive and only activated when a sufficient postsynaptic depolarization is induced by the activity. Here we show that in sensory synapses of adult mouse, some synaptic responses (26.3% of a total of 38 experiments) between primary afferent fibers and dorsal horn neurons are almost completely mediated by NMDA receptors. Dorsal root stimulation did not elicit any detectable AMPA/kainate receptor-mediated responses in these synapses. Unlike young spinal cord, serotonin alone did not produce any long-lasting synaptic enhancement in adult spinal dorsal horn neurons. However, co-application of the adenylyl cyclase activator forskolin and serotonin (5-HT) produced long-lasting enhancement, including the recruitment of functional AMPA receptor-mediated responses. Calcium-sensitive, calmodulin-regulated adenylyl cyclases (AC1, AC8) are required for the enhancement. Furthermore the thresholds for generating action potential responses were decreased, and, in many cases, co-application of forskolin and 5-HT led to the generation of action potentials by previously subthreshold stimulation of primary afferent fibers in the presence of the NMDA receptor blocker 2-amino-5-phosphonovaleric acid. Our results suggest that pure NMDA synapses exist on sensory neurons in adult spinal cord and that they may contribute to functional sensory transmission. The synergistic recruitment of functional AMPA responses by 5-HT and forskolin provides a new cellular mechanism for glutamatergic synapses in mammalian spinal cord.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2002

Presynaptic suppression of dorsal horn inhibitory transmission by mu-opioid receptors.

Opioids modify sensory experience at many levels in the CNS. The mechanisms of this action, including the ways opioid receptors affect synaptic transmission, are not yet fully understood. Here we show that the selective activation of mu-opioid receptors suppressed inhibitory transmission between spinal cord dorsal horn neurons in vitro. mu-Opioid receptor activation reduced evoked inhibitory postsynaptic current (eIPSC) amplitude by acting presynaptically, because it altered the paired-pulse ratio, did not affect GABA-evoked currents, and decreased miniature IPSC (mIPSC) frequency. The mechanism of this effect was independent both of presynaptic Ca(2+) entry and of the pathway linking presynaptic kainate (KA) receptors to suppression of inhibitory transmission in the same cells. These data identify mu-opioid receptors as important presynaptic modulators of dorsal horn inhibitory transmission.

Animals↗

PubMed2002

Glutamate and the presynaptic control of spinal sensory transmission.

Sensory neurons, in particular the small- and medium-diameter cells that sense painful stimuli, express both ionotropic and metabotropic glutamate receptors, which may regulate transmission between sensory neurons and their targets in the spinal cord dorsal horn. Although the roles that these receptors play in normal physiology are not completely understood, recent work has provided strong evidence for their ability to modulate transmitter release from primary afferent terminals.

Animals↗

PubMed2002

Genetic analysis of pain mechanisms.

Pain is the major reason for visits to the doctor. It is a complex sensation, with both a sensory and an emotional component. Its detailed regulation at all levels of the central nervous system, from the periphery to the cortex, has hindered our understanding of the neurobiological basis of pain. Furthermore, injury can produce long-lasting changes in pain pathways and chronic pain. The recent use of genetically modified organisms has significantly advanced our comprehension of the molecular and cellular mechanisms underlying pain. In this article we present the current state of knowledge regarding pain transmission, modulation, and plasticity, and some of the contributions made by studies of genetically altered mice. The cellular mechanisms explaining observed phenotypes, the involvement of supraspinal areas, and the plasticity underlying chronic pain are the three areas just beginning to be explored.

Animals↗