neuropeptide-y and Constriction--Pathologic

Neuropeptide tyrosine (NPY) and its associated receptors Y1R and Y2R have been previously implicated in the spinal modulation of neuropathic pain induced by total or partial sectioning of the sciatic nerve. However, their role in chronic constrictive injuries of the sciatic nerve has not yet been described. In the present study, we analyzed the consequences of pharmacological activation of spinal Y1R, by using the specific Y1R agonist Leu

Topics: Analysis of Variance; Animals; Chronic Pain; Cold Temperature; Constriction, Pathologic; Disease Models, Animal; Dose-Response Relationship, Drug; Hyperalgesia; Injections, Spinal; Male; Neuralgia; Neuropeptide Y; Pain Measurement; Pain Threshold; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide Y; Sciatic Nerve; Sciatic Neuropathy; Spinal Cord

The right gastroepiploic artery is useful as an in situ arterial graft for coronary artery bypass grafting. However, the gastroepiploic artery is more likely to cause vasospasms compared with the internal thoracic artery. We hypothesized that the cause of the spasms is the stimulation of the periarterial sympathetic nerve, because the gastroepiploic artery is classified as a muscular artery. In this study, we examined whether the spasm is reduced by removing the periarterial sympathetic nerve.. Unused parts of the gastroepiploic artery were obtained from patients who underwent coronary artery bypass grafting. The vessel was cut into 2 segments, and they were assigned to control (N+) and denervation (N-) groups. The periarterial nerve was microscopically removed from the vessels of the N- group. The vessels in both groups were investigated by hematoxylin-eosin or immunohistochemical staining, and they were stimulated by electrical field stimulation with serial frequency for isometric tension measurement.. Histologic analyses revealed that periarterial connective tissues including neuropeptide Y were removed to expose the external elastic membrane in the N- vessel, whereas they were preserved in N+. The mean contraction by electrical field stimulation with serial frequency was consistently lower in N- than in N+ (P < .05 at 20 and 50 Hz; n = 8 each). Endothelium-dependent relaxation and contractile function of the smooth muscle were similar in both groups.. The removal of the periarterial sympathetic nerve from the human gastroepiploic artery reduced vascular contraction, elicited by peripheral nerve stimulation, without disturbing endothelial and smooth muscle contractile functions. This reduction may contribute to the prevention of vasospasms.

Topics: Adrenergic Fibers; Arterial Occlusive Diseases; Biomarkers; Constriction, Pathologic; Electric Stimulation; Gastroepiploic Artery; Humans; Isometric Contraction; Neuropeptide Y; Sympathectomy; Vasoconstriction; Vasodilation

Single ligature nerve constriction (SLNC) of the rat sciatic nerve triggers neuropathic pain-related behaviors and induces changes in neuropeptide expression in primary afferent neurons. Bone marrow stromal cells (MSCs) injected into the lumbar 4 (L4) dorsal root ganglia (DRGs) of animals subjected to a sciatic nerve SLNC selectively migrate to the other ipsilateral lumbar DRGs (L3, L5 and L6) and prevent mechanical and thermal allodynia. In this study, we have evaluated the effect of MSC administration on the expression of the neuropeptides galanin and NPY, as well as the NPY Y(1)-receptor (Y(1)R) in DRG neurons. Animals were subjected to a sciatic nerve SLNC either alone or followed by the administration of MSCs, phosphate-buffered saline (PBS) or bone marrow non-adherent mononuclear cells (BNMCs), directly into the ipsilateral L4 DRG. Seven days after injury, the ipsilateral and contralateral L4-5 DRGs were dissected out and processed for standard immunohistochemistry, using specific antibodies. As previously reported, SLNC induced an ipsilateral increase in the number of galanin and NPY immunoreactive neurons and a decrease in Y(1)R-positive DRG neurons. The intraganglionic injection of PBS or BNMCs did not modify this pattern of expression. In contrast, MSC administration partially prevented the injury-induced changes in galanin, NPY and Y(1)R expression. The large number of Y(1)R-immunoreactive neurons together with high levels of NPY expression in animals injected with MSCs could explain, at least in part, the analgesic effects exerted by these cells. Our results support MSC participation in the modulation of neuropathic pain and give insight into one of the possible mechanisms involved.

Topics: Animals; Bone Marrow Cells; Constriction, Pathologic; Galanin; Neuropeptide Y; Rats; Receptors, Neuropeptide Y; Sciatic Nerve; Sciatic Neuropathy; Stem Cell Transplantation; Stromal Cells; Treatment Outcome; Wounds and Injuries

This study sought to investigate the effects of injury-induced neuropeptide Y (NPY) on c-Fos expression in the cuneate neurons and neuropathic pain after median nerve injury. Four weeks after median nerve transection (MNT), the injured nerves stimulated at low intensity (0.1 mA) expressed significantly less NPY-like immunoreactive (NPY-LI) fibers in the cuneate nucleus (CN) than those stimulated at high intensities (1.0 mA and 10 mA). Conversely, a significantly higher number of c-Fos-LI cells were observed in the CN in rats stimulated with 0.1 mA compared to those stimulated with 1.0 mA or 10 mA. These results suggest that more NPY was released following low-intensity stimulation, and consequently fewer NPY-LI fibers and more c-Fos-LI cells were identified in the CN. Furthermore, the number of c-Fos-LI cells as well as the percentage of c-Fos-LI cuneothalamic projection neurons (CTNs) in the CN was markedly decreased after injection of NPY receptor antagonist along with retrograde tract-tracing method, indicating that NPY regulated c-Fos expression. In rats with median nerve chronic constriction injury (CCI), intracerebroventricular injection of NPY aggravated mechanical allodynia and low-intensity stimulus-evoked c-Fos expression, both of which were reversed by injection of NPY receptor antagonist. However, thermal hyperalgesia was not affected by injection of these two reagents. Taken together, these findings suggest that more NPY release, following low-intensity electrical stimulation of the injured nerve, significantly induces c-Fos expression in the CTNs, which possibly provide the ascending thalamic transmission of neuropathic pain signals.

Topics: Animals; Behavior, Animal; Chronic Disease; Constriction, Pathologic; Electric Stimulation; Enzyme-Linked Immunosorbent Assay; Hyperalgesia; Injections, Intraventricular; Male; Median Nerve; Median Neuropathy; Medulla Oblongata; Neuropeptide Y; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide Y

Vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) in dorsal root ganglia (DRGs) are known to be upregulated and to contribute to the mechanisms of neuropathic pain following peripheral nerve injury. Moreover, transcription factor c-Jun regulates the expressions of both VIP and NPY in cultured DRG neurons. To elucidate the role of c-Jun in the induction of neuropathic pain hypersensitivity, we examined whether activated c-Jun affects pain behavior and the expressions of VIP and NPY following chronic constriction injury (CCI) of rat sciatic nerve. Intrathecal treatment with c-jun antisense oligodeoxynucleotides (AS-ODN) significantly reduced mechanical allodynia, but not thermal hyperalgesia following CCI. In addition, c-jun AS-ODN also suppressed the remarkable elevations of VIP and NPY mRNAs and the percentages of phosphorylated c-Jun-, VIP-, and NPY-immunoreactive neurons observed in DRGs following CCI. These results show that the activation of c-Jun in DRGs induces VIP and NPY upregulation and contributes to the pathogenesis of neuropathic pain following CCI.

Topics: Animals; Constriction, Pathologic; Ganglia, Spinal; Hot Temperature; Hypesthesia; Immunohistochemistry; Male; Neuralgia; Neurons; Neuropeptide Y; Oligonucleotides, Antisense; Phosphorylation; Physical Stimulation; Proto-Oncogene Proteins c-jun; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sciatic Nerve; Time Factors; Up-Regulation; Vasoactive Intestinal Peptide

The aim of this study was to investigate neuropeptide Y (NPY) levels in trigeminal ganglia following infraorbital nerve injury. Two experimental procedures were performed in three groups of rats: a unilateral chronic constriction injury (CCI) to the infraorbital nerve (n=13), nerve manipulation without CCI (n=13) and unoperated controls (n=8). All rats underwent baseline and regular assessment of mechanical withdrawal threshold (Von Frey) and reaction to pin prick as well as free behavior evaluations. CCI to the infraorbital nerve induced significant hyperalgesia and allodynia within 9-12 days. At 6 days seven rats were euthanized and trigeminal ganglia harvested for immunocytochemical (ICC) studies. The study was ended at 14 days when all rats were euthanized and their ganglia harvested for ICC and radioimmunoassay (RIA) studies. An increase in NPY levels was seen in the ipsilateral ganglia of manipulated and CCI rats at 6 days, when rats displayed no pain-related behavior. At 14 days, ICC and RIA both detected significant increases in NPY levels in the ipsilateral ganglia of CCI and manipulated rats but not in unoperated controls. The possible roles of NPY in pain modulation and nerve injury are discussed in light of these findings.

Topics: Animals; Constriction, Pathologic; Exploratory Behavior; Face; Grooming; Hyperalgesia; Immunohistochemistry; Male; Neuropeptide Y; Orbit; Physical Stimulation; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Trigeminal Ganglion; Trigeminal Nerve Injuries; Wounds and Injuries

This study has characterized constrictions of small cutaneous arteries in the guinea pig ear in response to electrical stimulation of the cervical sympathetic nerve (SNS) in vivo. Video microscopy and on-line image analysis were used to examine diameter changes of ear arteries (80-140 micrometers resting diameter) in anesthetized guinea pigs. Trains of 50-300 impulses, but not single pulses or short trains, produced frequency-dependent (2-20 Hz) constrictions. The purinoceptor antagonist suramin (30 microM) greatly reduced constrictions produced by exogenous ATP but did not affect constrictions produced by SNS at 10 Hz or exogenous norepinephrine. The alpha(2)-adrenoceptor antagonist yohimbine (1 microM) enhanced the peak amplitude of sympathetic constrictions at lower stimulation frequencies (1-5 Hz). The amplitude of constrictions to SNS at 10 Hz was reduced, and the latency of constrictions was increased by the alpha(1)-adrenoceptor antagonist prazosin (1 microM). Constrictions to SNS at 10 Hz remaining after prazosin treatment were reduced in amplitude by dihydroergotamine (2 microM) and were attenuated further by the neuropeptide Y Y(1)-receptor antagonist 1229U91 (0.3 microM). Thus norepinephrine and neuropeptide Y act as cotransmitters to mediate sympathetic constriction of small ear arteries at higher stimulation frequencies (10 Hz), but ATP does not seem to contribute directly to these constrictions.

Topics: Adenosine Triphosphate; Animals; Arteries; Constriction, Pathologic; Electric Stimulation; Female; Guinea Pigs; Male; Neurons; Neuropeptide Y; Norepinephrine; Peptides, Cyclic; Skin; Suramin; Sympathetic Nervous System; Vasoconstriction

Neuropeptide plasticity in the gracile nucleus is thought to play a role in the development of neuropathic pain following nerve injury. Two weeks after chronic constriction injury of adult rat sciatic nerve, galanin, neuropeptide Y and calcitonin gene-related peptide immunoreactivities were increased in fibers and cells in the gracile nucleus ipsilateral to injury. At the electron microscopic level, this increased neuropeptide immunoreactivity was localized in myelinated axons, boutons, dendrites, neurons and glial cells. Galanin-, neuropeptide Y- and calcitonin gene-related peptide-immunoreactive boutons were frequently presynaptic to dendrites of both immunoreactive and non-immunoreactive neurons. However, no neuropeptide Y, galanin and calcitonin gene-related peptide messenger RNA was detected in the injured side gracile nuclei by in situ hybridization. These results show that partial nerve injury to the sciatic nerve induces increases in the content of galanin, neuropeptide Y and calcitonin gene-related peptide immunoreactivities in synaptic terminals within the gracile nucleus, which suggests that there may be increased release of these neuropeptides following sensory or spontaneous stimulation of large-diameter primary afferents following partial nerve injury, perhaps one mechanism involved in neuropathic pain. We also show an apparent transfer of these neuropeptides to the cells of the gracile nucleus, both neurons and glial cells, an intriguing phenomenon of unknown functional significance.

Topics: Animals; Axons; Calcitonin Gene-Related Peptide; Chronic Disease; Constriction, Pathologic; Galanin; Immunohistochemistry; In Situ Hybridization; Male; Medulla Oblongata; Microscopy, Immunoelectron; Neurons; Neuropeptide Y; Neuropeptides; Presynaptic Terminals; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sciatic Nerve

The distribution of neuropeptide Y (NPY)-immunoreactive (IR) primary afferents in the dental pulp and periodontal ligament of the rat mandible were examined following combined chronic constriction injury (CCI) of the inferior alveolar nerve (IAN) and sympathectomy of the superior cervical ganglion (SCG). NPY-IR nerve fibers were observed around the blood vessels in the trigeminal ganglion, dental pulp and periodontal ligament in normal animals. Following combined CCI of the IAN and sympathectomy of SCG (SCGx), perivascular NPY-IR nerve fibers originating from SCG disappeared completely, but many NPY-IR nerve fibers coming from the trigeminal ganglion appeared in the dental pulp and periodontal ligament. In the molar dental pulp, thick NPY-IR nerve fibers were observed within the nerve bundle, and some thin NPY-IR nerve fibers ran towards the odontoblast layer; very few NPY-IR nerve fibers were observed in the incisor pulp. In the periodontal ligament of molar, thick NPY-IR nerve fibers appeared at the alveolar part following combined CCI of IAN and SCGx. In the lingual portion of the periodontal ligament of the incisor, many thick NPY-IR nerve fibers were observed. These occasionally showed a tree-like appearance, resembling immature Ruffini endings; slowly adapting mechanoreceptors. The present results indicate that periodontal mechanoreceptors are among the main targets of injury-evoked NPY following IAN injury.

Topics: Afferent Pathways; Animals; Constriction, Pathologic; Dental Pulp; Immunohistochemistry; Mandible; Nerve Fibers; Neuropeptide Y; Periodontal Ligament; Rats; Rats, Sprague-Dawley; Superior Cervical Ganglion; Trigeminal Ganglion; Trigeminal Nerve Injuries

This study examines the influence of renal nerves on the development of renovascular hypertension in proximal aortic constricted rats. The rats were studied 1 week after unilateral or bilateral denervation of the renal artery. Denervation had no effect on the increase in mean arterial pressure induced by the constriction. The glomerular filtration rate and filtration fraction in control and in proximal aortic constricted rats were not influenced by the denervation. The Na excretion was increased in the denervated kidney both in control and in proximal aortic constricted rats. Plasma angiotensin II levels were not different from controls in innervated or unilaterally denervated proximal aortic constricted rats. In bilaterally denervated proximal aortic constricted rats the plasma angiotensin II levels were significantly higher. The renovascular hypertension and the alteration in renal function in proximal aortic constricted rats are not dependent on renal nerve activity.

Topics: Angiotensin II; Animals; Aorta, Abdominal; Blood Pressure; Calcitonin Gene-Related Peptide; Constriction, Pathologic; Denervation; Hypertension, Renovascular; Kidney; Male; Neurons, Afferent; Neuropeptide Y; Rats; Rats, Inbred Strains; Sodium