Endotoxin-Induced Uveitis Causes Long-Term Changes in Trigeminal Subnucleus Caudalis Neurons

2005 ◽  
Vol 94 (6) ◽  
pp. 3815-3825 ◽  
Author(s):  
David A. Bereiter ◽  
Keiichiro Okamoto ◽  
Akimasa Tashiro ◽  
Harumitsu Hirata

Endotoxin-induced uveitis (EIU) is commonly used in animals to mimic ocular inflammation in humans. Although the peripheral aspects of EIU have been well studied, little is known of the central neural effects of anterior eye inflammation. EIU was induced in male rats by endotoxin or lipopolysaccharide (LPS, 1 mg/kg ip) given 2 or 7 days earlier. Neurons responsive to mechanical stimulation of the ocular surface were recorded under barbiturate anesthesia at the trigeminal subnucleus interpolaris/caudalis (Vi/Vc) transition and subnucleus caudalis/cervical cord (Vc/C1) junction, the main terminal regions for corneal nociceptors. Two days after LPS, Vc/C1 units had reduced responses to histamine, nicotine, and CO2 gas applied to the ocular surface, whereas unit responses were increased 7 days after LPS. Those units with convergent cutaneous receptive fields at Vc/C1 were enlarged 7 days after LPS. Units at the Vi/Vc transition also had reduced responses to histamine and CO2 2 days after LPS but no enhancement was seen at 7 days. Tear volume evoked by CO2 was reduced 2 days after LPS and returned toward control values by 7 days, whereas CO2-evoked eye blinks were normal at 2 days and increased 7 days after LPS. These results indicate that a single exposure to endotoxin causes long-term changes in the excitability of second-order neurons responsive to noxious ocular stimulation. The differential effects of EIU on tear volume and eye blink lend further support for the hypothesis that ocular-sensitive neurons at the Vi/Vc transition and Vc/C1 junction regions mediate different aspects of pain during intraocular inflammation.

1999 ◽  
Vol 82 (5) ◽  
pp. 2092-2107 ◽  
Author(s):  
Harumitsu Hirata ◽  
James W. Hu ◽  
David A. Bereiter

Corneal-responsive neurons were recorded extracellularly in two regions of the spinal trigeminal nucleus, subnucleus interpolaris/caudalis (Vi/Vc) and subnucleus caudalis/upper cervical cord (Vc/C1) transition regions, from methohexital-anesthetized male rats. Thirty-nine Vi/Vc and 26 Vc/C1 neurons that responded to mechanical and electrical stimulation of the cornea were examined for convergent cutaneous receptive fields, responses to natural stimulation of the corneal surface by CO2 pulses (0, 30, 60, 80, and 95%), effects of morphine, and projections to the contralateral thalamus. Forty-six percent of mechanically sensitive Vi/Vc neurons and 58% of Vc/C1 neurons were excited by CO2 stimulation. The evoked activity of most cells occurred at 60% CO2 after a delay of 7–22 s. At the Vi/Vc transition three response patterns were seen. Type I cells ( n = 11) displayed an increase in activity with increasing CO2 concentration. Type II cells ( n = 7) displayed a biphasic response, an initial inhibition followed by excitation in which the magnitude of the excitatory phase was dependent on CO2 concentration. A third category of Vi/Vc cells (type III, n = 3) responded to CO2 pulses only after morphine administration (>1.0 mg/kg). At the Vc/C1 transition, all CO2-responsive cells ( n = 15) displayed an increase in firing rates with greater CO2 concentration, similar to the pattern of type I Vi/Vc cells. Comparisons of the effects of CO2 pulses on Vi/Vc type I units, Vi/Vc type II units, and Vc/C1 corneal units revealed no significant differences in threshold intensity, stimulus encoding, or latency to sustained firing. Morphine (0.5–3.5 mg/kg iv) enhanced the CO2-evoked activity of 50% of Vi/Vc neurons tested, whereas all Vc/C1 cells were inhibited in a dose-dependent, naloxone-reversible manner. Stimulation of the contralateral posterior thalamic nucleus antidromically activated 37% of Vc/C1 corneal units; however, no effective sites were found within the ventral posteromedial thalamic nucleus or nucleus submedius. None of the Vi/Vc corneal units tested were antidromically activated from sites within these thalamic regions. Corneal-responsive neurons in the Vi/Vc and Vc/C1 regions likely serve different functions in ocular nociception, a conclusion reflected more by the difference in sensitivity to analgesic drugs and efferent projection targets than by the CO2 stimulus intensity encoding functions. Collectively, the properties of Vc/C1 corneal neurons were consistent with a role in the sensory-discriminative aspects of ocular pain due to chemical irritation. The unique and heterogeneous properties of Vi/Vc corneal neurons suggested involvement in more specialized ocular functions such as reflex control of tear formation or eye blinks or recruitment of antinociceptive control pathways.


2017 ◽  
Vol 39 (5) ◽  
pp. 386-398
Author(s):  
Cheryl C.H. Yang ◽  
Shiang-Suo Huang ◽  
Chun-Ting Lai ◽  
Terry B.J. Kuo ◽  
Ya-Chun Chu

Neonatal, short-lasting, local, nociceptive insult by carrageenan can cause long-term alterations in somatosensory and neurohumoral systems. We previously revealed hyporesponsiveness of the autonomic nervous system (ANS) after painful stimulation of adult rats in a neonatal carrageenan-induced pain model. Sleep disturbance has been highly correlated with pain and ANS activity. In the present study, adult rats that had received an intraplantar injection of carrageenan on postnatal day 1 were investigated to determine if there were alterations in their sleep architecture upon the stimulation of pain. Polysomnographic and heart rate variability recordings were carried out, with a wireless transmission of data, for 24 h under baseline conditions and after an intraplantar injection of complete Freund's adjuvant to induce sustained nociception. Increased active awake (AW) and decreased quiet sleep (QS) and paradoxical sleep (PS) times were noted in the control animals. In the carrageenan-treated rats, the AW time increased but with decreased alertness, as revealed by decreases in beta and increases in theta power. The QS time did not decrease. The PS time decreased during the first 12 h, then increased during the following 12 h, suggesting an early rebound of formerly deprived PS time. Sympathetic activation under sustained pain was not apparent in any stage of sleep in carrageenan-treated rats and was even suppressed in AW time. An impaired sympathetic reaction to pain may have contributed to the atypical changes in sleep architecture in these rats. In conclusion, pain in early life has a long-term effect on the cardiovascular-autonomic-electroencephalographic responses to pain later in life. The physiological relevance of these results remains undetermined.


2012 ◽  
Vol 108 (10) ◽  
pp. 2668-2678 ◽  
Author(s):  
Yu Wang ◽  
Yi Chen ◽  
Lu Chen ◽  
Jonathan R. Wolpaw ◽  
Xiang Yang Chen

The cortex gradually modifies the spinal cord during development, throughout later life, and in response to trauma or disease. The mechanisms of this essential function are not well understood. In this study, weak electrical stimulation of rat sensorimotor cortex increased the soleus H-reflex, increased the numbers and sizes of GABAergic spinal interneurons and GABAergic terminals on soleus motoneurons, and decreased GABAA and GABAB receptor labeling in these motoneurons. Several months after the stimulation ended the interneuron and terminal increases had disappeared, but the H-reflex increase and the receptor decreases remained. The changes in GABAergic terminals and GABAB receptors accurately predicted the changes in H-reflex size. The results reveal a new long-term dimension to cortical-spinal interactions and raise new therapeutic possibilities.


2019 ◽  
Author(s):  
R.J. Flores ◽  
F.Z. Alshbool ◽  
P. Giner ◽  
L.E. O’Dell ◽  
I.A. Mendez

AbstractBackgroundPrevious studies have shown that exposure to nicotine smoke increases impulsivity. Surprisingly, research investigating the effects of electronic cigarette nicotine vapor exposure on impulsivity has not been conducted. Therefore, the present study examined the effects of nicotine vapor exposure on impulsive choice.MethodsTwenty-four adult male rats were trained in the delay discounting task to choose between small immediate food rewards or larger food rewards with delayed deliveries. After 24 days of training in the delay discounting task, rats were passively exposed to vapor containing either 0, 12, or 24 mg/mL of nicotine for 10 days. To monitor exposure to nicotine, serum cotinine levels were assessed on exposure days 1, 5, and 10 using enzyme-linked immunosorbent assay (ELISA). Following vapor exposure, rats were retrained in the delay discounting task until stable performance was achieved, and the effects of nicotine vapor exposure on choice preference were assessed.ResultsRats that were exposed to 12 and 24 mg/mL nicotine vapor displayed higher serum cotinine levels, relative to those exposed to 0 mg/mL nicotine vapor. There were no differences in impulsive choice between any of the vapor groups when tested 15-21 days after exposure. However, increases in impulsive choice were observed when testing immediately following exposure to 24 mg/mL nicotine vapor, relative to immediately following exposure to 0 mg/mL nicotine vapor.ConclusionsFindings suggest that while exposure to nicotine vapor may not cause long-term changes in decision making, it can cause short-term increases in impulsive choice, an effect that can have negative social and health consequences.


1997 ◽  
Vol 77 (6) ◽  
pp. 3107-3114 ◽  
Author(s):  
Marcello A. Caria ◽  
Takeshi Kaneko ◽  
Akihisa Kimura ◽  
Hiroshi Asanuma

Caria, Marcello A., Takeshi Kaneko, Akihisa Kimura, and Hiroshi Asanuma. Functional organization of the projection from area 2 to area 4γ in the cat. J. Neurophysiol. 77: 3107–3114, 1997. It has been shown that tetanic stimulation of area 2 of the somatosensory cortex produces long-term potentiation in neurons in area 4γ, and this has been suggested as the basis of learning new motor skills. The purpose of this study was to further elucidate the characteristics of this projection by the use of evoked potentials in area 4γ elicited by intracortical microstimulation of area 2. The experiments were carried out in cats and the following results were obtained. 1) In six animals, stimulation of a given site in area 2 elicited evoked potentials in a restricted region of area 4γ, the size of which ranged from 1 to 1.5 mm2. These responses were labeled “localized responses.” The evoked potentials were recorded from the superficial layers of the cortex, and were positive monophasic in shape. 2) In 16 animals, stimulation of a given site in area 2 elicited a focal response that was surrounded by smaller positive and monophasic potentials of <50% amplitude that spread broadly over area 4γ. These responses were labeled “graded responses.” 3) The sites that produced focal evoked potentials in area 4γ extended along the direction of the radial fibers in area 2. These sites were defined as most effective segments (MESs). 4) The receptive fields of neurons along the MES in area 2 were similar to those of neurons recorded at the foci of the evoked potentials in area 4γ. The results demonstrate that some of the projections from area 2 to area 4γ are highly specific and that the somatosensory and motor areas that are connected by these specific projections receive functionally related peripheral input. These results are discussed in relation to possible mechanisms underlying motor learning.


2019 ◽  
Vol 33 (12) ◽  
pp. 1524-1532 ◽  
Author(s):  
Milene Cristina de Carvalho ◽  
Rebeca Machado de Figueiredo ◽  
Norberto Cysne Coimbra ◽  
Christie Ramos Andrade Leite-Panissi ◽  
Maria Angélica de Souza Silva ◽  
...  

Purpose: Intranasally applied dopamine (IN-DA), which likely reaches the brain via nasal–brain pathways and bypasses the blood–brain barrier, has been found to increase extracellular DA and bind to the DA2 transporter in the striatum. Recent studies suggest that DA plays a significant role in the processing of signaled and unconditioned aversive stimulation, including evidence that may attenuate responses to painful input. The purpose of this study was to examine the effects of IN-DA on fear-related behaviors induced by electric shock to the foot or by electrical stimulation of the dorsal periaqueductal gray matter (dPAG). Methods: DA hydrochloride suspended in a viscous castor oil gel (1 or 2 mg/kg) was applied (IN-DA) in a volume of 5 μL into the nostrils of adult Wistar male rats in order to evaluate its effects on (a) freezing induced by electric shock to the foot and (b) thresholds of freezing and escape and duration of post-stimulation freezing induced by electrical stimulation of the dPAG. Results: IN-DA attenuated freezing induced by electric shock to the foot in the three test trials, indicating that it reduced long-term fear responses. IN-DA also increased the threshold of dPAG stimulation-induced escape responses and reduced post-stimulation freezing. Conclusions: IN-DA, which has previously been shown to facilitate learning and to have antidepressive-like effects, attenuated unconditioned fear responses elicited by peripheral and intramesencephalic (dPAG) stimulation and reduced long-term conditioned fear responses.


1977 ◽  
Vol 84 (4) ◽  
pp. 813-828 ◽  
Author(s):  
Rachel Hamburger-Bar ◽  
Henk Rigter

ABSTRACT The effects of androgens on the maintenance and restoration of sexual behaviour (mounts, intromissions and ejaculations) of castrated male rats were studied. In the maintenance study the rats were treated during 5 weeks, starting one day following castration. Testosterone propionate maintained sexual behaviour at an almost normal level. The androgenoestrogen intermediate 19-hydroxytestosterone propionate was unable to prevent the decline in the number of ejaculations over the weeks although this hormone maintained the post-ejaculatory refractory period in those rats that ejaculated and also maintained normal sexual latencies. In the restoration study administration of testosterone propionate during 7 weeks to long-term castrated rats restored sexual behaviour to normal. 19-Hydroxytestosterone propionate treated rats displayed mounts but no other signs of sexual behaviour. The 5α-reduced androgen dihydrotestosterone propionate did not restore sexual behaviour. Testosterone propionate and dihydrotestosterone propionate stimulated peripheral target organs; 19-hydroxytestosterone propionate was ineffective in this respect. It has been suggested that testosterone might stimulate sexual behaviour in rats in two ways, i. e., via its aromatization to oestradiol in the brain, and by stimulating growth of peripheral tissues via its 5α-reduction to dihydrotestosterone. In support for this view we have found that the combination of 19-hydroxytestosterone propionate and dihydrotestosterone propionate was effective in restoring the full pattern of sexual behaviour in castrated male rats.


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