Dopaminergic Modulation of Orofacial Mechanical Hypersensitivity Induced by Infraorbital Nerve Injury.

While the descending dopaminergic control system is not fully understood, it is reported that the hypothalamic A11 nucleus is its principle source. To better understand the impact of this system, particularly the A11 nucleus, on neuropathic pain, we created a chronic constriction injury model of the infraorbital nerve (ION-CCI) in rats. ION-CCI rats received intraperitoneal administrations of quinpirole (a dopamine D2 receptor agonist). ION-CCI rats received microinjections of quinpirole, muscimol [a gamma-aminobutyric acid type A (GABAA) receptor agonist], or neurotoxin 6-hydroxydopamine (6-OHDA) into the A11 nucleus. A von Frey filament was used as a mechanical stimulus on the maxillary whisker pad skin; behavioral and immunohistochemical responses to the stimulation were assessed. After intraperitoneal administration of quinpirole and microinjection of quinpirole or muscimol, ION-CCI rats showed an increase in head-withdrawal thresholds and a decrease in the number of phosphorylated extracellular signal-regulated kinase (pERK) immunoreactive (pERK-IR) cells in the superficial layers of the trigeminal spinal subnucleus caudalis (Vc). Following 6-OHDA microinjection, ION-CCI rats showed a decrease in head-withdrawal thresholds and an increase in the number of pERK-IR cells in the Vc. Our findings suggest the descending dopaminergic control system is involved in the modulation of trigeminal neuropathic pain.

Neuropeptide RFRP inhibits the pacemaker activity of terminal nerve GnRH neurons.

The terminal nerve gonadotropin-releasing hormone (TN-GnRH) neurons show spontaneous pacemaker activity whose firing frequency is suggested to regulate the release of GnRH peptides and control motivation for reproductive behaviors. Previous studies of the electrophysiological properties of TN-GnRH neurons reported excitatory modulation of pacemaker activity by auto/paracrine and synaptic modulations, but inhibition of pacemaker activity has not been reported to date. Our recent study suggests that neuropeptide FF, a type of Arg-Phe-amide (RFamide) peptide expressed in TN-GnRH neurons themselves, inhibits the pacemaker activity of TN-GnRH neurons in an auto- and paracrine manner. In the present study, we examined whether RFamide-related peptides (RFRPs), which are produced in the hypothalamus, modulate the pacemaker activity of TN-GnRH neurons as candidate inhibitory synaptic modulators. Bath application of RFRP2, among the three teleost RFRPs, decreased the frequency of firing of TN-GnRH neurons. This inhibition was diminished by RF9, a potent antagonist of GPR147/74, which are candidate RFRP receptors. RFRP2 changed the conductances for Na(+) and K(+). The reversal potential for RFRP2-induced current was altered by inhibitors of the transient receptor potential canonical (TRPC) channel (La(3+) and 2-aminoethoxydiphenyl borate) and by a less selective blocker of voltage-independent K(+) channels (Ba(2+)). By comparing the current-voltage relationship in artificial cerebrospinal fluid with that under each drug, the RFRP2-induced current was suggested to consist of TRPC channel-like current and voltage-independent K(+) current. Therefore, synaptic release of RFRP2 from hypothalamic neurons is suggested to inhibit the pacemaker activity of TN-GnRH neurons by closing TRPC channels and opening voltage-independent K(+) channels. This novel pathway may negatively regulate reproductive behaviors.

[Effect of transection or pretreatment of the infraorbital nerve with snake venom on the analgesia induced by electroacupuncture of "Sibai" (ST 2) acupoint in visceral pain rats].

OBJECTIVE: To observe the role of large-diameter fibers of infraorbital nerve (ION) in "Sibai" (ST 2)-electroacupuncture (EA) induced analgesia in visceral pain (VP) rats. METHODS: A total of 36 SD rats were randomized into control, VP, EA, ION transaction, snake venom (SV) and saline groups, with 6 rats in each group. EA(2 Hz/20 Hz) was applied to bilateral "Sibai" (ST 2) for 20 min. VP model was established by intraperitoneal injection of 0.6% acetic acid (10 mL/kg). Bilateral ION were transacted or pretreated by regional application of snake venom to selectively destroy A fibers,respectively. Behavior reactions were assessed by counting abdominal muscular contractions. Meanwhile, c-fos expression in the nucleus of the solitary tract (NTS) and paratrigeminal nucleus (PTN) was displayed by immunohistochemistry. RESULTS: In comparison with control group, the numbers of abdominal muscular contraction,and c-fos immuno-reaction (IR) positive neurons in both NTS and PTN increased significantly in VP group (P < 0.001); while in comparison with VP group, the numbers of the abdominal contraction, and c-fos IR-positive neurons of both NTS and PTN in EA and SV and saline groups decreased considerably (P < 0.05, P < 0.01). No significant differences were found between ION transaction and VP groups in the abdominal contraction number, and c-fos IR-positive neurons in both NTS and PTN areas,and among EA and SV and saline groups in the numbers of abdominal contraction and c-fos IR-positive neurons of both NTS and PTN (P > 0.05). CONCLUSION: The large-diameter (A) fibers of ION are not the major afferent fibers affecting EA-ST 2 induced analgesia in visceral pain rats; and somatic sensory afferents from orofacial areas and visceral pain input converge in the NTS and PTN, which may be the basis of the EA analgesia in the present study.

Age-related changes of elements with their relationships in human cranial and spinal nerves.

To elucidate compositional changes of peripheral nerves with aging, the authors investigated age-related changes of elements and their relationships in the optic, trigeminal, vagus, median, radial, ulnar, femoral, sciatic, tibial, and common peroneal nerves by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of 10 men and 12 women, ranging in age from 65 to 91 yr. It was found that although accumulations of Ca and P occurred only in the trigeminal nerve at old age, it hardly occurred in the optic, vagus, median, radial, ulnar, femoral, sciatic, tibial, and common peroneal nerves at old age. The average contents of Ca and P were three and two times higher in the trigeminal nerve than in the other nine kinds of nerve, respectively. Likewise, the average content of Mg was a little higher in the trigeminal nerve compared with the other nerves. With regard to the relationships among elements, significant direct correlations were found among the contents of Ca, P, S, and Mg in most, but not all, 10 kinds of nerve. In the trigeminal nerve, a significant inverse correlation was found between the contents of S and the other elements, such as Ca, P, and Mg. Regarding the relationships between the contents of S and other elements, the nerves, except for the trigeminal nerve, differed from those found in the arteries previously reported.

Expression and function of Xenopus laevis p75(NTR) suggest evolution of developmental regulatory mechanisms.

Neurotrophins signal through two different classes of receptors, members of the trk family of receptor tyrosine kinases, and p75 neurotrophin receptor (p75(NTR)), a member of the tumor necrosis factor receptor family. While neurotrophin binding to trks results in, among other things, increased cell survival, p75(NTR) has enigmatically been implicated in promoting both survival and cell death. Which of these two signals p75(NTR) imparts depends on the specific cellular context. Xenopus laevis is an excellent system in which to study p75(NTR) function in vivo because of its amenability to experimental manipulation. We therefore cloned partial cDNAs of two p75(NTR) genes from Xenopus, which we have termed p75(NTR)a and p75(NTR)b. We then cloned two different cDNAs, both of which encompass the full coding region of p75(NTR)a. Early in development both p75(NTR)a and p75(NTR)b are expressed in developing cranial ganglia and presumptive spinal sensory neurons, similar to what is observed in other species. Later, p75(NTR)a expression largely continues to parallel p75(NTR) expression in other species. However, Xenopus p75(NTR)a is additionally expressed in the neuroepithelium of the anterior telencephalon, all layers of the retina including the photoreceptor layer, and functioning axial skeletal muscle. Finally, misexpression of full length p75(NTR) and each of two truncated mutants in developing retina reveal that p75(NTR) probably signals for cell survival in this system. This result contrasts with the reported role of p75(NTR) in developing retinae of other species, and the possible implications of this difference are discussed.

Distribution of luteinizing hormone-releasing hormone in the nervus terminalis and brain of the mouse detected by immunocytochemistry.

Immunoreactive luteinizing hormone-releasing hormone (LHRH) was localized in a relatively large number of ganglion cells and fibers of the nervus terminalis of neonatal and adult mice, indicating that this nerve is a substantial source of LHRH in the mouse brain. Whole-head specimens of neonatal mice, prior to calcification of the cranium, revealed an extensive distribution of LHRH neurons and fine fibers throughout the peripheral, intracranial, and central parts of the nervus terminalis. The most striking difference between the neonatal and adult animals, in the nervus terminalis, was the increase in immunoreactive axons that made up the fiber bundles of this nerve. In the adult mouse, the intracranial and central projections were composed of thick fascicles of immunoreactive axons, ensheathed by glial cells and accompanied by ganglia that contained both LHRH-reactive and nonimmunoreactive neurons. LHRH-immunoreactive cells and axons were seen in a branch of the nervus terminalis that coursed along the medial, posterodorsal aspect of the olfactory bulb and in branches of this nerve that accompany the vomeronasal nerves to the accessory olfactory bulb. A few LHRH neurons and many immunoreactive processes were seen in the accessory and main olfactory bulbs. LHRH-reactive neurons were seen in the hypothalamus and extrahypothalamic structures. Examination of adult mouse brains revealed a pattern of distribution and number of immunoreactive neurons similar to that seen in the neonate. However, many more LHRH-reactive axons were seen in all areas of the brain of the mature animal.

Locations of androgen-concentrating cells in the brain of Xenopus laevis: autoradiography with 3H-dihydrotestosterone.

The distribution of hormone-concentrating cells in the brains of South African clawed frogs, Xenopus laevis, was examined autoradiographically after the administration of 3H-dihydrotestosterone. Hormone-accumulating cells were found in cranial nerve nucleus IX-X and adjacent smaller cells, a presumed medullary vestibular nucleus, a presumed sensory nucleus of cranial nerve V, dorsal tegmental area of the medulla, laminar nucleus of the torus semicircularis, ventral thalamus, and anterior pituitary. The pattern of dihydrotestosterone-labelled cells differs from previously reported results following testosterone or estradiol administration. Unlike these latter hormones, dihydrotestosterone does not accumulate in anterior preoptic or ventral infundibular nuclei. Both androgens but not estradiol label medullary motor neurons; limbic telencephalic nuclei appear to concentrate only estradiol. Hormone-concentrating brain nuclei in X. laevis have been implicated in neuro-endocrine regulation and the control of male and female reproductive behaviors.