Biomedical subjects

H S Na

Publications and source records attributed to H S Na.

At least 19 recordsLinked to original sources

PubMed2001

Sympathetic sprouting in sensory ganglia depends on the number of injured neurons.

We examined whether the extent of sympathetic sprouting in the dorsal root ganglion was a function of the number of injured nerve fibers. We compared two groups of rats. One group was subjected to unilateral superior and inferior caudal trunk transections at the level between the S1 and S2 spinal nerves (S-I group) and the other group was subjected to unilateral superior caudal trunk transection at the same level (S group). Immunohistochemical staining with tyrosine hydroxylase (TH) antibody of the S1 DRG revealed that the degree of TH-immunoreactive fibers was more extensive in the S-I group than in the S group. However, there was no difference in the severity of neuropathic pain behaviors between the two groups. These results suggest that the extent of sympathetic sprouting in the DRG following peripheral nerve injury is proportionally related to the amount of injured nerve fibers, but not related to the degree of neuropathic pain behaviors.

Adrenergic Fibers↗

PubMed2001

A novel method for convenient assessment of arthritic pain in voluntarily walking rats.

Quantification of arthritic pain can be very useful in elucidating the mechanisms of arthritis and in assessing the effect of anti-arthritic medication or treatment. Here we report a novel method that allows convenient measurements of the severity of arthritic pain in voluntarily walking rats. We constructed a device to measure the weight load on each leg while the animal was walking through a path, the bottom of which was equipped with strain gauge weight sensors. Using this device, we measured the weight load on the right hind leg before and after induction of arthritis by carrageenan injection into the knee joint cavity of this leg. The carrageenan injection resulted in a significant reduction of weight load on the affected leg; the load decreased to the minimum level at 4 h after the injection and gradually returned to the pre-injection level by the fifth day. Intraperitoneal administration of morphine at 5.5 h after carrageenan injection could reverse the weight load change. These results suggest that our new device is an effective tool for convenient measurements of arthritic pain in dynamic conditions like walking.

Analgesics, Opioid↗

PubMed2001

Substance p plays a critical role in photic resetting of the circadian pacemaker in the rat hypothalamus.

Glutamate is considered to be the primary neurotransmitter in the retinohypothalamic tract (RHT), which delivers photic information from the retina to the suprachiasmatic nucleus (SCN), the locus of the mammalian circadian pacemaker. However, substance P (SP) also has been suggested to play a role in retinohypothalamic transmission. In this study, we sought evidence that SP from the RHT contributes to photic resetting of the circadian pacemaker and further explored the possible interaction of SP with glutamate in this process. In rat hypothalamic slices cut parasagittally, electrical stimulation of the optic nerve in early and late subjective night produced a phase delay (2.4 +/- 0.5 hr; mean +/- SEM) and advance (2.6 +/- 0.3 hr) of the circadian rhythm of SCN neuronal firing activity, respectively. The SP antagonist L-703,606 (10 microm) applied to the slices during the nerve stimulation completely blocked the phase shifts. Likewise, a cocktail of NMDA (2-amino-5-phosphonopentanoic acid, 50 microm) and non-NMDA (6,7-dinitroquinoxaline-2,3-dione, 10 microm) antagonists completely blocked the shifts. Exogenous application of SP (1 microm) or glutamate (100 microm) to the slices in early subjective night produced a phase delay ( approximately 3 hr) of the circadian firing activity rhythm of SCN neurons. Coapplication of the NMDA and non-NMDA antagonist cocktail (as well as L-703,606) resulted in a complete blockade of the SP-induced phase delay, whereas L-703,606 (10 microm) had no effect on the glutamate-induced delay. These results suggest that SP, as well as glutamate, has a critical role in photic resetting. Furthermore, the results suggest that the two agonists act in series, SP working upstream of glutamate.

Animals↗

PubMed2001

Decrease in spinal CGRP and substance P is not related to neuropathic pain in a rat model.

We tested the hypothesis that the decrease in spinal levels of SP and CGRP after peripheral nerve injury is related to neuropathic pain. We compared two groups of rats, both of which were subjected to unilateral transection of the inferior and superior caudal trunks between the S1 and S2 spinal nerves. One group exhibited well-developed neuropathic signs after the nerve injury, whereas the other group showed poorly developed signs despite the same nerve injury. The decrease in immunoreactivity of CGRP and SP in the S1 dorsal horn (injured segment) was not significantly different between the two groups. These results suggest that the decrease in spinal levels of CGRP and SP after peripheral nerve injury is not related to neuropathic pain.

Animals↗

PubMed2001

Desensitization to urine-derived gonadotropins in a woman with secondary infertility.

BACKGROUND: Urine-derived gonadotropins have been used to treat infertility but may cause allergic reactions. IgE-mediated hypersensitivity reactions can be treated with desensitization, especially when new therapies such as recombinant human gonadotropins are unavailable. OBJECTIVE: This case is described to highlight a successful intervention with desensitization in a woman with a complicated history of secondary infertility. She had been treated with ovulation-induction regimens, such as IVF-M (in vitro fertilization-human menopausal gonadotropin [hMG]) and IVF-C (human chorionic gonadotropin [hCG]), for intrauterine insemination. During treatment, however, she experienced reactions to IVF-M and IVF-C. Because she strongly wanted a baby and no alternative preparation was available, desensitization was attempted. METHODS: Intradermal tests with IVF-M and IVF-C using both negative and positive controls were performed on the patient and four normal control subjects. Immediate wheal-and-flare reactions occurred only in the patient. ELISA and ELISA inhibition tests showed positive responses to IVF-M and IVF-C, but not to highly purified hMG, hCG, or D-mannitol, a preservative in IVF-M and IVF-C. Desensitization to IVF-M and IVF-C was done with a protocol used for parenteral desensitization to penicillin. RESULTS: During the IVF-M desensitization, the intramuscular injections were well tolerated. For the next 2 days, daily administration of IVF-M was uneventful. Thirty-six hours later, desensitization to IVF-C was performed successfully. The patient had two intrauterine inseminations and became pregnant. CONCLUSIONS: Nongonadotropin proteins in urine-derived gonadotropins cause IgE-mediated hypersensitivity reactions. Acute desensitization to urine-derived gonadotropins can be performed effectively, as shown in our current case.

Adult↗

PubMed2000

Role of signals from the dorsal root ganglion in neuropathic pain in a rat model.

We examined whether signals from the neuroma or the dorsal root ganglion of the injured segment are critical for the generation of neuropathic pain. To this aim, we used a rat model of peripheral neuropathy made by transecting the inferior and superior caudal trunks at the level between the S1 and S2 spinal nerves under enflurane anesthesia. These animals displayed tail-withdrawal responses to normally innocuous mechanical stimulation applied to the tail with a von Frey hair (2 g). Also, these animals, compared to pre-surgical value, displayed shorter tail-withdrawal latencies following immersion of the tail to warm (40 degrees C) or cold (4 degrees C) water. Transection of the S1 spinal nerve between the dorsal root ganglion and neuroma did not change the behavioral signs of neuropathic pain. In contrast, S1 dorsal rhizotomy significantly reduced the behavioral signs. The data suggest that signals arising from the dorsal root ganglion cells of the injured segment, but not from the neuroma, are critical for the generation of neuropathic pain in this model.

Animals↗

PubMed1999

Electrophysiological evidence for the role of substance P in retinohypothalamic transmission in the rat.

The retinohypothalamic tract (RHT) is a neural pathway through which photic time cues are delivered directly to the mammalian circadian pacemaker in the suprachiasmatic nucleus (SCN). Although the excitatory amino acid glutamate is the primary neurotransmitter in the RHT, other substances such as substance P (SPq also have been suggested to play a role. The present study tested the hypothesis that SP participates in retinohypothalamic transmission and selectively modulates either N-methyl-D-aspartate (NMDA) or non-NMDA receptor-mediated neurotransmission. The SP antagonist L-703,606 depressed the excitatory postsynaptic current (EPSC) evoked by optic nerve stimulation in SCN neurons in rat hypothalamic slices. The SP antagonist also had a similar depressive effect on the NMDA and non-NMDA receptor-mediated components of the EPSC. These results suggest that SP is an excitatory neuromodulator contributing to the expression of both the NMDA and non-NMDA receptor-mediated components of retinohypothalamic transmission.

2-Amino-5-phosphonovalerate↗

PubMed1999

Is sympathetic sprouting in the dorsal root ganglia responsible for the production of neuropathic pain in a rat model?

Partial peripheral nerve injury often results in neuropathic pain that is aggravated by sympathetic excitation and induces sympathetic nerve sprouting in both the injured nerve and corresponding dorsal root ganglia (DRGs). Presently, the functional mechanisms of the interactions between the sprouting and injured somatic afferents remain uncertain. This study was performed to see whether the sprouting in the DRGs plays a key role in the development of neuropathic pain. To this aim, we compared two groups of rats, both of which were subjected to unilateral transection of the superior and inferior caudal trunks at the level between the S1 and S2 spinal nerves, with respect to sympathetic fiber sprouting; one group showed well-developed neuropathic pain behaviors (i.e. mechanical, cold and warm allodynia signs) and the other group showed poorly-developed ones. Immuno-histochemical staining with tyrosine hydroxylase (TH) antibody of the injured S1 DRG taken from both groups of rats after behavioral tests revealed that the magnitude of penetration of TH-positive fibers into the S1 DRG was not significantly different between the two groups. These results suggest that sympathetic nerve sprouting in the injured DRG is not a key factor in the development of neuropathic pain.

Animals↗

PubMed1999

Some membrane property changes following axotomy in A delta-type DRG cells are related to cold allodynia in rat.

Numerous studies have suggested that changes in electrophysiological properties of primary sensory neurons after axonal injury contribute to the generation of neuropathic pain. Presently, however, it is unclear which of the changes is important. To address this issue, we performed behavioral and electrophysiological experiments in a double-blind fashion; we made intracellular recordings in the S1 dorsal root ganglia excised from rats exhibiting cold allodynia behavior after chronic S1 spinal nerve transaction (allodynia-positive group) and from rats lacking such behavior after the same nerve injury (allodynia-negative group) or sham injury (sham group). In this study, we sought which of the membrane property changes produced by the spinal nerve injury in each of C-, Adelta- and Aalpha/beta-cell populations was unique to the allodynia-positive group. Analyses of our data revealed that only some changes in Adelta-cells (e.g. the decrease in resting membrane potential and in the threshold of central process) were more pronounced in or unique to the allodynia-positive group. We concluded that certain membrane property changes in the somata and dorsal root axons of Adelta-cells might be important in the generation of cold allodynia.

Action Potentials↗

PubMed1998

Supraspinal involvement in the production of mechanical allodynia by spinal nerve injury in rats.

This study examined whether or not the production of mechanical allodynia in a rat model of neuropathic pain required an involvement of supraspinal site(s). To this aim, we assessed the effect of spinal cord section at the L1 segment level on the mechanical allodynia sign (i.e. tail flick/twitch response), which was elicited by innocuous von Frey hair stimulation of the tail after unilateral transection of the tail-innervating nerve superior caudal trunk (SCT) at the level between the S3 and S4 spinal nerves. Cord transection or hemisection of the cord ipsilateral to the injured SCT drastically (though not completely) blocked the behavioral sign of mechanical allodynia (leaving noxious pinprick-elicited tail withdrawal reflex intact), whereas sham section or contralateral hemisection of the cord was without effect. These results suggest that the generation of mechanical allodynia following partial peripheral nerve injury involves transmission of the triggering sensory signal to a site(s) rostral to the L1 segment via an ipsilateral pathway(s).

Animals↗

PubMed1998

Amount of sympathetic sprouting in the dorsal root ganglia is not correlated to the level of sympathetic dependence of neuropathic pain in a rat model.

Incomplete peripheral nerve injury often leads to neuropathic pains, some of which are relieved by sympathectomy, and results in sympathetic postganglionic nerve fiber sprouting in the dorsal root ganglion (DRG). This study was performed to see whether the sprouting in the DRG plays a key role in the sympathetic dependence of neuropathic pain. To this aim, we compared two groups of rats, both of which were subjected to unilateral transection of the inferior and superior caudal trunks at the levels between the S1 and S2, S2 and S3, and S3 and S4 spinal nerves, with respect to sympathetic fiber sprouting; one group showed neuropathic pain behaviours (i.e. mechanical and cold allodynia signs) which were very sensitive to phentolamine, alpha adrenergic blocker, and the other group exhibited no sensitivity. Immuno-histochemical staining with tyrosine hydroxylase antibody of the S1-S3 DRGs was not correlated with the sensitivity to phentolamine. These results suggest that the degree of sympathetic dependence of neuropathic pain is not a function of the extent of the sympathetic postganglionic nerve fiber sprouting in the DRG.

Adrenergic alpha-Antagonists↗

PubMed1998

Cell type-specific changes of the membrane properties of peripherally-axotomized dorsal root ganglion neurons in a rat model of neuropathic pain.

Recent evidence indicates that neuropathic pain from partial peripheral nerve injury is maintained by electrophysiologically abnormal signals from injured sensory neurons. To gain an insight into the mechanisms underlying this electrophysiological abnormality, we examined the effects of S1 spinal nerve transection on the membrane properties of S1 dorsal root ganglion neurons one to two weeks after injury. This injury produced significant action potential broadening [40% (1 ms) in C-, 149% (1.5 ms) in A delta- and 84% (0.5 ms) in A alpha/beta-cells], which was primarily due to the enhancement of the "shoulder" appearing on the falling phase of the action potential in C- and A delta-cells and the emergence of a shoulder in A alpha/beta-cells, and significant cell-type specific changes in the time-course of the rising phase of the action potential; i.e. an increase in rise time (A delta: 35%, 0.15 ms; A alpha/beta: 13%, 0.04 ms) and a decrease in the maximal rate of rise (A delta: 17%, 77 V/s; A alpha/beta: 13%, 79 V/s). In addition, the nerve injury led to a significant reduction of the rheobase, an index of neuronal excitability, in all types of cells (by 41% in C-, 71% in A delta- and 59% in A alpha/beta-cells). The reduction of rheobase in A-cells was associated with a concomitant increase in apparent input resistance (by 269% in A delta- and 192% in A alpha/beta-cells), which was measured near the resting membrane potential. By contrast, the rheobase reduction in C-cells was associated with a concurrent depolarizing shift (approximately 4 mV) of the resting membrane potential. The nerve injury-induced reduction of rheobase was not accompanied by related change in input resistance or threshold potential in any of the cell populations. The present results indicate that chronic peripheral axotomy of dorsal root ganglion neurons, which gives rise to neuropathic pain, produces profound changes in the action potential waveform of dorsal root ganglion neurons in a cell type-specific fashion. Furthermore, the results suggest that the axotomy increases the excitability of dorsal root ganglion neurons not by altering input resistance (i.e. leak conductance) or threshold potential, but by increasing apparent input resistance near the resting membrane potential in A-cells and decreasing the resting membrane potential in C-cells.

Action Potentials↗

PubMed1997

NMDA receptors are important for both mechanical and thermal allodynia from peripheral nerve injury in rats.

Previous studies showed that heat-hyperalgesia and mechanical allodynia produced by chronic constrictive injury of the sciatic nerve were differentially sensitive to the NMDA receptor antagonist dextrorphan and to morphine and other opioid receptor agonists. These results support the hypothesis that different kinds of neuropathic pain symptoms are caused by different pathological mechanisms. In the present study we determined whether mechanical and thermal allodynia produced by unilateral transection of the 'superior' caudal trunk which innervates the tail in rats were differentially sensitive to the non-competitive NMDA receptor antagonist MK-801. Injection of MK-801 (0.3 mg/kg, i.p.) prior to nerve injury delayed the emergence of both types of allodynia; the antagonist-treated rats exhibited neither mechanical nor thermal allodynia at least for 4 days after the injury, whereas untreated control rats exhibited clear signs of allodynia from the first day after the injury. MK-801 injection on post-injury day 14, when the allodynia was near peak severity, suppressed temporarily both the mechanical and thermal allodynia. These results suggest that the mechanical and thermal allodynia from partial denervation of the tail are both dependent on NMDA receptors in their induction and maintenance. Thus, our results do not support the notion that different pathological mechanisms underlie different modalities of neuropathic pain from partial peripheral nerve injury.

Animals↗

PubMed1996

Sprouting of sympathetic nerve fibers into the dorsal root ganglion following peripheral nerve injury depends on the injury site.

Peripheral nerve injury often induces sympathetic nerve fiber sprouting in the dorsal root ganglion (DRG) and injured nerve. Presently, the underlying mechanism and functional significance of the sprouting are unknown. This study was performed to see whether the degree of the sprouting in the DRG was a function of the distance between the DRG and injury site. To this aim, we compared two groups of rats with respect to the sympathetic nerve fibers sprouting in the S1-3 DRG; one group was subjected to unilateral inferior and superior caudal trunk transections at the level between the S3 and S4 spinal nerves (S34 group) and the other group at the levels between the S1 and S2, between S2 and S3 and between S3 and S4 spinal nerves (S123 group). The transections in both groups equally eliminated the inputs from the tail to the S1-3 DRG, but the distance from the S1/S2 DRG to the injury site was different between the two groups. Immunohistochemical staining with tyrosine hydroxylase (TH) antibody of the S1-3 DRG removed from rats a week after the injury revealed that the degree of penetration of TH-positive fibers into the S1 and S2 DRG was much more extensive in the S123 group than in the S34 group, whereas that into the S3 DRG was not significantly different between the two groups. These results suggest that the extent of the sympathetic nerve fiber sprouting in the DRG following peripheral nerve injury is inversely related to the distance between the DRG and injury site.

Animals↗

PubMed1996

Ventricular premature beat-driven intermittent restoration of coronary blood flow reduces the incidence of reperfusion-induced ventricular fibrillation in a cat model of regional ischemia.

With a cat model of regional cardiac ischemia, we examined whether the incidence of reperfusion-induced ventricular fibrillation (VF) could be reduced by ventricular premature beat (VPB)-driven intermittent reperfusion. In addition, we assessed whether the effect of the intermittent reperfusion was comparable with that of ischemic preconditioning in suppressing the VF. Of 15 cats subjected to uninterrupted reperfusion after 20-minute occlusion of the left anterior descending coronary artery, 13 (86.70%) had VF, whereas only 1 (7.1%) of 14 cats subjected to the VPB-driven intermittent reperfusion had VF. This incidence of VF was significantly lower than that of the animal group subjected to uninterrupted reperfusion. However, it was not statistically different from that (3 of 15) of the group subjected to a 10-minute episode of the coronary artery occlusion before the 20-minute occlusion (i.e., "ischermic preconditioning"). Our results suggest that the VPB-driven intermittent reperfusion (i.e., "postconditioning") is very effective in preventing reperfusion-induced VF and as good as, if not better than, ischemic preconditioning.

Animals↗

PubMed1995

Mechanical allodynia is more strongly manifested in older rats in an experimental model of peripheral neuropathy.

Partial peripheral nerve injury often leads to chronic neuropathic pain characterized by symptoms such as allodynia. In the present study, employing a rat model of experimental neuropathy produced by partial denervation of the tail, we examined whether peripheral nerve injury-induced mechanical and thermal allodynia were affected by the animal's age at the time of the injury. The motive of this study was the demonstration in other neuropathy models of the age effects on the manifestation of neuropathic pain symptoms following partial peripheral nerve injury. We compared two groups of young (n = 23, 7-8 weeks old, 150-200 g) and old rats (n = 14, 16-18 months old, 550-800 g). We found that the older rats exhibited more vigorously the behavioral signs of mechanical allodynia during the first week after the nerve injury. With respect to thermal (cold or warm) allodynia, however, we detected no significant difference between young and old rat groups. The results of the present study, as those of previous studies, support the idea that the age at the time of partial peripheral nerve injury affects the severity of certain neuropathic pain symptoms appearing after the injury. However, the present results argue against the suggestion from previous studies that younger subjects are more vulnerable to partial peripheral nerve injury-induced neuropathic pain symptoms.

Aging↗

PubMed1995

Effects of age on behavioral signs of neuropathic pain in an experimental rat model.

The present study examined the effect that aging has on the manifestations of pain behaviors in a rat model of neuropathic pain. Two experiments were conducted. The first experiment compared young, mature and old rats. After tight ligation of the L5 and L6 segmental spinal nerves, young rats displayed much more vigorous behavioral signs of mechanical allodynia and ongoing pain than did either mature or old rats. The second experiment was done using the same rats at two different time points. Spinal nerve ligation was done on the left side of rats when they were young and the same surgery was repeated on the right side 20 weeks later (mature age). Comparison of pain behaviors between the left and right sides confirmed the results of the first experiment. The data suggest that younger rats show much more robust behavioral signs of neuropathic pain compared to older rats.

Aging↗

PubMed1995

Critical role of the capsaicin-sensitive nerve fibers in the development of the causalgic symptoms produced by transecting some but not all of the nerves innervating the rat tail.

We investigated the role of capsaicin-sensitive small diameter fibers in the development of the thermal and mechanical allodynia in a new rat model for neuropathic pain, produced by transecting some but not all of the nerves innervating the tail. Capsaicin (50 mg/kg, s.c.) injected neonatally prior to the nerve injury produced thermal hypoalgesia in the tail the degree of which was variable across individual rats, presumably as a result of variable degeneration of the small diameter fibers. When subjected to the nerve injury, the animals with moderate thermal hypoalgesia exhibited signs of pain (e.g., tail flick) to normally innocuous mechanical stimuli applied to the tail with von Frey hairs (4.9 mN or 19.6 mN bending force), but not to thermal stimuli given by immersion of the tail into cold (4 degrees C) or warm (40 degrees C) water. The animals with marked thermal hypoalgesia, on the other hand, exhibited no signs of pain either to the mechanical or to the thermal stimuli. These results suggest that the capsaicin-sensitive fibers are critical in the development of both the mechanical and thermal allodynia. It is hypothesized that the destruction of A delta- and C-nociceptive fibers by capsaicin prevented activities induced in these fibers by the nerve injury from producing a central sensitization and thus allodynia.

Animals↗