Obesity is a prevalent disease with significant morbidity and mortality. It is a state of chronic low-grade inflammation due to excess body fat. Weight homeostasis is maintained through changes in various gastrointestinal hormones caused by dietary intake. However, being overweight or obese breaks the balance of these appetite-related gastrointestinal hormones and creates resistance to the actions of these hormones. The sensitivity of vagal afferent neurons to peripheral signals becomes blunted. Cytokines produced by excessive fat tissue damage our normal immune system, making us vulnerable to infection. In addition, various changes in gastrointestinal motility occur. Therefore, this review focuses on the various changes in gastrointestinal hormones, the immune state, the vagus nerve, and gastrointestinal movement in obese patients.
Adipose Tissue ; Cytokines ; Gastrointestinal Hormones ; Gastrointestinal Motility ; Homeostasis ; Humans ; Immune System ; Inflammation ; Mortality ; Neurons, Afferent ; Obesity ; Overweight ; Physiology ; Vagus Nerve

The rostral ventromedial medulla (RVM) is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 receptor (MC4R) expression in the RVM, where the neurons involved in modulation of nociception reside. Using a line of mice expressing green fluorescent protein (GFP) under the control of the MC4R promoter, we found a large number of GFP-positive neurons in the RVM [nucleus raphe magnus (NRM) and nucleus gigantocellularis pars α (NGCα)]. Fluorescence immunohistochemistry revealed that approximately 10% of MC4R-GFP-positive neurons coexpressed tyrosine hydroxylase, indicating that they were catecholaminergic, whereas 50%-75% of those coexpressed tryptophan hydroxylase, indicating that they were serotonergic. Our findings support the hypothesis that MC4R signaling in RVM may modulate the activity of serotonergic sympathetic outflow sensitive to nociceptive signals, and that MC4R signaling in RVM may contribute to the descending modulation of nociceptive transmission.
Animals ; Female ; Male ; Medulla Oblongata ; cytology ; metabolism ; Mice ; Mice, Transgenic ; Neural Pathways ; cytology ; metabolism ; Neurons, Afferent ; cytology ; metabolism ; Nociception ; physiology ; Receptor, Melanocortin, Type 4 ; genetics ; metabolism ; Serotonergic Neurons ; metabolism ; Tyrosine 3-Monooxygenase ; metabolism

Sciatic nerve injury is a common disease of peripheral nerve in clinic. After nerve injury, there are many dysfunctions in motoneurons and muscles following regeneration. Previous studies mostly investigated the aspects related to the injured nerve, and the effect on the recurrent inhibition (RI) pathway of spine following regeneration was not fully understood. Following reinnervation after temporary sciatic nerve crush, the functional alteration of RI was studied. In adult rats, RI between lateral gastrocnemius-soleus (LG-S) and medial gastrocnemius (MG) motor pools was assessed by conditioning monosynaptic reflexes (MSRs) elicited from the cut dorsal roots and recorded from either the LG-S or MG nerves by antidromic stimulation of the synergist muscle nerve. The following results were obtained. (1) The RI of MSRs in rats was almost lost (<5 weeks) after sciatic nerve crush. Although the RI partially recovered following reinnervation (6 weeks), it remained permanently depressed (up to 14 weeks). (2) Sciatic nerve crush on one side did not affect the contralateral RI. (3) Sciatic nerve crush did not induce any motoneuron loss revealed by immunohistochemistry. Peripheral nerve temporary disconnection causes long term alterations in RI pathway which make up motoneuron's function enhance for the alteration of muscle power and suggests that peripheral nerve injury induces long term plastic changes in the spinal motoneuron circuitry.
Animals ; Long-Term Synaptic Depression ; physiology ; Male ; Motor Neurons ; physiology ; Nerve Crush ; Nerve Regeneration ; physiology ; Neuronal Plasticity ; physiology ; Neurons, Afferent ; physiology ; Rats ; Rats, Wistar ; Reflex, Monosynaptic ; physiology ; Sciatic Nerve ; injuries ; physiopathology ; Spinal Cord ; physiopathology ; Spinal Nerve Roots ; physiopathology

The sleep-wake cycle displays a characteristic 24-hour periodicity, providing an opportunity to dissect the endogenous circadian clock through the study of aberrant behaviour. This article surveys the properties of circadian clocks, with emphasis on mammals. Information was obtained from searches of peer-reviewed literature in the PUBMED database. Features that are highlighted include the known molecular components of clocks, their entrainment by external time cues and the output pathways used by clocks to regulate metabolism and behaviour. A review of human circadian rhythm sleep disorders follows, including recent discoveries of their genetic basis. The article concludes with a discussion of future approaches to the study of human circadian biology and sleep-wake behaviour.
ARNTL Transcription Factors ; Animals ; Basic Helix-Loop-Helix Transcription Factors ; physiology ; CLOCK Proteins ; Circadian Rhythm ; genetics ; physiology ; Humans ; Neurons, Afferent ; physiology ; Neurons, Efferent ; physiology ; Polymorphism, Single Nucleotide ; Sleep Disorders, Circadian Rhythm ; genetics ; physiopathology ; Suprachiasmatic Nucleus ; cytology ; physiology ; Trans-Activators ; physiology

AIMTo explore the influence of GABAergic neurotransmitters and GABAA receptors on the auditory afferent impulses recorded in the brainstem evoked by electro-stimulation.

METHODSBrainstem slices were prepared using ddy/ddy mice of postnatal 0-5th days. The brainstem slices were stained with a voltage-sensitive dye(NK3041). The cut end of the vestibulocochlear nerve (nVIIIth) connected with slices was stimulated by a tungsten electrode, a 16 x 16 pixels silicon photodiode array apparatus was used to record the optical mapping from auditory brainstem slices. The data were analyzed by ARGUS-50/PDA software.

RESULTSThe spatial-temporal patterns of the excitatory propagation from the vestibulocochlear nerve (nVIIIth) to cochlear nucleus and vestibular nucleus were displayed with multiple-sites optical recording. The optical signal coming from one pixel consisted of a fast spike-like response and a following slow response. Inhibitory neurotransmitter GABA decreased the fast spike-like response and following slow response of evoked optical signals, while an antagonist BMI against GABAA receptors increased the both responses.

CONCLUSIONA 16 x 16 pixel silicon photodiode array apparatus can be used to record multiple-sites optical mapping evoked by electro-stimulation to the cut end of the vestibulocochlear nerve. The every optical signal consists of both presynaptic and postsynaptic elements. Inhibitory neurotransmitter GABA and an antagonist BMI of GABAA receptors can modulate the excitatory propagation of evoked optical signals.

Animals ; Animals, Newborn ; Auditory Pathways ; physiology ; Brain Stem ; physiology ; Evoked Potentials, Auditory, Brain Stem ; physiology ; In Vitro Techniques ; Mice ; Neurons, Afferent ; physiology ; Optics and Photonics ; Photic Stimulation ; Receptors, GABA-A ; physiology ; gamma-Aminobutyric Acid ; physiology

OBJECTIVETo study the relationship between substance P (SP) and/or calcitonin gene-related peptide (CGRP) immunoreactive neurons in dorsal root ganglia (DRG) and the transmission of nociception in the penile frenulum of rats.

METHODSThe fluoro-gold (FG) retrograde tracing method was used to trace the origin of nerve terminals in the penile frenulum of rats. And SP and/or CGRP immunofluorescence labeling was employed to detect the distribution of SP and/or CGRP immunoreactive neurons in DRG.

RESULTSFG retrograde tracing showed that the FG retrolabeled neurons were localized in L6-DRG and S1-DRG. SP and/or CGRP immunofluorescence labeling indicated that a large number of DRG neurons were SP- and CGRP-immunoreactive, different in size, bright red and bright green respectively in color, and arranged in rows or spots among nerve bundles. All the FG/SP and FG/CGRP double-labeled neurons were medium or small-sized. One third of the FG-labeled neurons were SP-immunoreactive, and a half of them CGRP-immunoreactive in L6-DRG and S1-DRG respectively. The FG/SP/CGRP-labeled neurons accounted for one fifth of the FG retro labeled neurons.

CONCLUSIONSP- and CGRP-immunoreactive neurons in L6-DRG and SI-DRG of rats may be involved in the transmission of nociception in rat penile frenulum.

Animals ; Calcitonin Gene-Related Peptide ; analysis ; Ganglia, Spinal ; chemistry ; cytology ; Male ; Microscopy, Fluorescence ; Neurons ; chemistry ; physiology ; Neurons, Afferent ; chemistry ; physiology ; Penis ; innervation ; Rats ; Rats, Sprague-Dawley ; Substance P ; analysis

OBJECTIVETo explicate the spinal nerve source of the rabbit penis cutaneous sensation.

METHODSTwelve adult male rabbits were randomly divided into two groups of equal number. While mechanical stimuli were given to the penis by different von Frey hairs, single fiber activities were recorded in vivo in the left (Group A) and right (Group B) S1-S4 spinal nerves, respectively. The mechanical threshold, adaptability and conduction velocity of the fibers were analyzed.

RESULTSWhen the ipsilateral penis was mechanically stimulated, discharges were detected in S2 and S3 spinal nerve fibers, but not in S1 and S4. The discharge fibers were 39.67 +/- 3.14 (S2) and 21.00 +/- 2.19 (S3) in the left spinal nerve and 40.00 +/- 3.16 (S2) and 19.67 +/- 2.58 (S3) in the right. There was no obvious difference between the numbers of the left spinal nerves and the right ones (P > 0.05).

CONCLUSIONThe rabbit penis cutaneous sensation originates from S2 and S3 spinal nerves.

Animals ; Electrophysiology ; Male ; Neurons, Afferent ; physiology ; Penis ; Rabbits ; Random Allocation ; Sensory Thresholds ; Skin ; innervation ; Spinal Nerves ; physiology

The excitability of nociceptive neurons increases in the intact dorsal root ganglion (DRG) after a chronic compression, but the underlying mechanisms are still unclear. The aim of this study was to investigate the ionic mechanisms underlying the hyperexcitability of nociceptive neurons in the compressed ganglion. Chronic compression of DRG (CCD) was produced in adult rats by inserting two rods through the intervertebral foramina to compress the L4 DRG and the ipsilateral L5 DRG. After 5-7 d, DRG somata were dissociated and placed in culture for 12-18 h. In sharp electrode recording model, the lower current threshold and the depolarized membrane potential in the acutely dissociated CCD neurons were detected, indicating that hyperexcitability is intrinsic to the soma. Since voltage-gated K(+) (Kv) channels in the primary sensory neurons are important for the regulation of excitability, we hypothesized that CCD would alter K(+) current properties in the primary sensory neurons. We examined the effects of 4-aminopyridine (4-AP), a specific antagonist of A-type potassium channel, on the excitability of the control DRG neurons. With 4-AP in the external solution, the control DRG neurons depolarized (with discharges in some cells) and their current threshold decreased as the CCD neurons demonstrated, indicating the involvement of decreased A-type potassium current in the hyperexcitability of the injured neurons. Furthermore, the alteration of A-type potassium current in nociceptive neurons in the compressed ganglion was investigated with the whole-cell patch-clamp recording model. CCD significantly decreased A-type potassium current density in nociceptive DRG neurons. These data suggest that a reduction in A-type potassium current contributes, at least in part, to the increase in neuron excitability that may lead to the development of pain and hyperalgesia associated with CCD.
Animals ; Female ; Ganglia, Spinal ; physiopathology ; Hyperalgesia ; etiology ; physiopathology ; Neurons, Afferent ; physiology ; Nociceptors ; physiology ; Pain ; physiopathology ; Potassium Channels ; physiology ; Radiculopathy ; physiopathology ; Rats ; Rats, Sprague-Dawley

Objective A calcium-activated chloride current (IClCa) has been observed in medium-sized sensory neurons of the dorsal root ganglion (DRG). Axotomy of the sciatic nerve induces a similar current in the majority of medium and large diameter neurons. Our aim is to identify the molecule(s) underlying this current. Methods Using conventional and quantitative RT-PCR, we examined the expression in DRG of members of three families of genes, which have been shown to have IClCa current inducing properties. Results We showed the detection of transcripts representing several members of these families, i.e. chloride channel calcium-activated (CLCA), Bestrophin and Tweety gene families in adult DRG, in the normal state and 3 d after sciatic nerve section, a model for peripheral nerve injury. Conclusion Our analysis revealed that that mBest1 and Tweety2 appear as the best candidates to play a role in the injury-induced IClCa in DRG neurons.
Animals ; Axotomy ; Chloride Channels ; biosynthesis ; genetics ; DNA Primers ; Ganglia, Spinal ; metabolism ; Gene Expression ; Mice ; Neurons, Afferent ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sciatic Nerve ; physiology

The neurophysiology of itch, the dominant symptom of skin disease, has previously received scant attention. Recent advances in the neurophysiology and molecular basis of itch include the use of microneurography to demonstrate the existence of a subset of itch-dedicated afferent C neurons distinct from neurons which transmit pain; use of functional positron emission tomography (PET) and magnetic resonance imaging (MRI) of the brain to reveal an itch-specific activation matrix, and new evidence of a functional "dialogue" between C neuron terminals and dermal mast cells in which recently described proteinase-activated receptor type 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) receptors, proteases and endovanilloids play a major role. As a necessary prerequisite to diagnosis and management, a pathophysiologically based classification of itch is proposed. Recent advances in understanding of the pathomechanisms of itch of cholestasis include the role of opioids and opioid antagonists. Focusing on neurogenic itch (itch without visible rash), common causes are reviewed and guidelines for laboratory and radiological investigation are proposed. A stepwise approach to management of generalised itch is recommended, including broadband or narrow band ultraviolet (UV), tricyclics such as doxepin, opioid antagonists including naltrexone and selective serotonin reuptake inhibitors (SSRIs) such as paroxetine. For troublesome localised itches such as insect bite reactions, physical urticaria, lichen simplex chronicus or, less commonly, notalgia paraesthetica, brachioradial pruritus, local cooling devices which rely on the cooling action of dimethyl ethers on thermosensitive TRP voltage-sensitive ion channels are now commercially available for shortterm relief.
Antipruritics ; therapeutic use ; Diagnosis, Differential ; Diagnostic Imaging ; methods ; Humans ; Neurons, Afferent ; physiology ; Pruritus ; diagnosis ; physiopathology ; therapy ; Treatment Outcome ; Ultraviolet Therapy ; methods