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At least 775 records · Page 43Linked to original sources
PubMed1977

Effects of type A botulinum toxin on the cholinergic transmission at spinal Renshaw cells and on the inhibitory action at Ia inhibitory interneurones.

1. The central action of botulinum toxin A (BTA) on the cholinergic transmission at Renshaw cells (RCs) and on the RC-induced inhibition of Ia inhibitory interneurones (IaINs) was studied in anaesthetized cats. BTA was administered by application directly into the spinal cord, injection into a ventral root (L7) and/or injection into the triceps surae (GS) muscle. 2. A direct application of BTA into the spinal cord led to a decrease of the early and the late response of RCs. 3. When the neurotoxin was injected into the GS muscle, the RC activity remained unaffected during the test period (33-46 h after application). 4. No effect appeared up to 10 h after an injection into the ventral root L7. 5. The RC-induced inhibition on IaINs, when tested in animals with local botulismus, remained intact during the test period. 6. From the present results it is suggested that on the spinal level the central action of botulinum toxin predominantly passes on the motoneurones.

Action Potentials↗
PubMed1998

NMDA receptors mediating Fos expression in rat spinal cord induced by subcutaneous injection of formalin.

AIM: To examine the effects of N-methyl-D-aspartate (NMDA) and non-NMDA receptors on noxious stimulation-induced Fos expression in the rat spinal cord. METHODS: Formalin (2%) was injected s.c. into one hindpaw of the rat. Fos expression was exhibited by immunocytochemical technique. RESULTS: Two hours after s.c. formalin, Fos-like immunoreactive (FLI) neurons were distributed mainly in medial part of the lamina I and the outer lamina II of the ipsilateral dorsal horn. dl-2-Amino-5-phosphonovalerate (APV) administered intrathecally (10 microL, 0.01, 0.1, or 1 g.L-1) before injection of formalin into a hindpaw reduced the number of FLI neurons dose-dependently in the dorsal horn (P < 0.01), while 6,7-dinitroquinoxaline-2, 3(1H,4H)-dione (DNQX) (1 g.L-1) was ineffective. CONCLUSION: NMDA receptor mediated noxious stimulation-induced Fos expression in the rat spinal cord.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

Intrathecally injected antibody can diffuse into spinal cord.

Antibody microinjection has been widely used to investigate the function of neuropeptides, but the capability of antibody to diffuse in the brain tissue has not been well characterized. The present study was conducted with an immunohistochemical method to determine if the anti-enkephalin serum injected intrathecally could diffuse into the spinal cord. Enkephalin immunoreactivity was observed in laminae I and II in slight amounts after 10 min, in moderate amounts after 30 minutes and very clearly after 60 min of the intrathecal injection of enkephalin antiserum. In addition, marked nonspecific staining was observed in the dorsal part but not in the ventral part of the white matter. These results indicate that antibodies injected intrathecally are capable of diffusing into the spinal cord within a time period of 10-60 min.

Animals↗
PubMed2003

Role of micro-opioid receptors in formalin-induced pain behavior in mice.

Intraplantar formalin injection is widely used as an experimental model of tonic pain. We investigated the role of endogenous micro-opioid receptor mechanisms in formalin-induced nocifensive behavior in mice. The flinching response induced by formalin (2%, 20 microl) was studied in mice with normal (wild type, n = 8) and absent (homozygous micro-opioid receptor knockout, n = 8) micro-opioid receptor levels. The flinch responses were counted every 5 min for 60 min post-formalin injection. Lumbar spinal cord (L4, 5) was harvested 2 h post-formalin injection to examine c-Fos expression using immunohistochemistry. The effects of naloxone (5 mg/kg, sc) administered 30 min before the intraplantar formalin injection on the flinching response of wild-type mice (n = 7) were also recorded. The second-phase formalin response (10-60 min after formalin) was higher in homozygous micro-opioid receptor knockout mice compared to the wild-type mice (P < 0.01). Naloxone administration in wild-type mice before formalin injection resulted in pain behavior similar to that observed in homozygous micro-opioid receptor knockout mice (P > 0.05). The c-Fos expression induced by formalin injection in the knockout mice was not different from that observed in wild-type mice. Our results suggest that the endogenous micro-opioid system is activated by intraplantar formalin injection and exerts a tonic inhibitory effect on the pain behavior. These results suggest an important modulatory role of endogenous micro-opioid receptor mechanisms in tonic pain states.

Animals↗
PubMed1989

A study of corticospinal remodelling using retrograde fluorescent tracers in rats.

The retrogradely transported fluorescent tracers Fast Blue (FB) and Diamidino Yellow (DY) were injected into the spinal cord of adult rats that sustained unilateral frontoparietal cortical lesions at birth. Analysis of the resulting cortical labeling pattern in comparison to comparably injected control animals demonstrated an increase of retrogradely-labeled neurons within the unablated cerebral hemisphere ipsilateral to spinal cord injections. These ipsilateral labeled cells corresponded to previous descriptions, based on anterograde tracing techniques, of anomalous uncrossed corticospinal tract (CST) fibers. Additional findings indicated that the ipsilateral CST fibers are not axonal collaterals of normal, crossed CST fibers. Fluorescent tracer injections into cervical and lumbar spinal cord levels demonstrated a distribution pattern of labeled cells within the ipsilateral cortex that was similar to the topographic pattern found contralateral to spinal cord injections in normal animals. These findings support previous anatomical and electrophysiological data indicating that the neonatal cortical lesion-induced increase of ipsilateral CST fibers may be functional.

Animals↗
PubMed1990

Spinal antinociception: comparison of a dermorphin tetrapeptide analogue, [D-arginine2, sarcosine4]-dermorphin (1-4) and morphine in rats.

Intracerebroventricular injections of [D-arginine2, sarcosine4]-dermorphin (1-4) (DAS-DER 1-4) and morphine produced a dose-dependent inhibition of the tail-flick response to thermal stimulation. The ED50 value for each drug was 3.23 (1.35-7.73) nmol/rat and 32.0 (13.3-76.6) nmol/rat, respectively. When injected into the spinal subarachnoid space, the ED50 value was 0.035 (0.015-0.086) nmol/rat for the tetrapeptide and 11.9 (5.7-25.2) nmol/rat for morphine, respectively. Antinociception induced by DAS-DER 1-4 and morphine, through the intracerebroventricular and intrathecal routes, was clearly reduced by pretreatment with a small dose of naloxone. After spinal transection, the antinociceptive potency of systemically-administered morphine was significantly reduced while that of DAS-DER 1-4 was unaltered. The activity of DAS-DER 1-4 and morphine was also reversed by naloxone in spinal animals. It is concluded that DAS-DER 1-4, a dermorphin analogue, has a minor supraspinal action but acts mainly at the level of the spinal cord, in contrast to the action of morphine.

Analgesics↗
PubMed1995

Changes in the electrophysiological properties of cat spinal motoneurons following the intramuscular injection of adriamycin compared with changes in the properties of motoneurons in aged cats.

1. This study was undertaken to investigate the effects of adriamycin (ADM, Doxorubicin) on the basic electrophysiological properties of spinal cord motoneurons in the adult cat. ADM was injected into the biceps, gastrocnemius, semitendinosus, and semimembranosus muscles of the left hindlimb (1.2 mg per muscle). Intracellular recordings from motoneurons innervating these muscles were carried out 12, 20, or 40 days after ADM administration and from corresponding motoneurons in untreated control cats. 2. Twelve days after ADM injection, motoneurons innervating ADM-treated muscles (ADM MNs) exhibited statistically significant increases in input resistance, membrane time constant, and amplitude of the action potential's afterhyperpolarization (AHP). In addition, there was a statistically significant decrease in rheobase and in the delay between the action potential of the initial segment (IS) and that of the somadendritic (SD) portion of the motoneuron (IS-SD delay). There were no significant changes in the resting membrane potential, threshold depolarization, action potential amplitude, or axonal conduction velocity. 3. The changes in electrical properties of motoneurons at 20 and 40 days after ADM injection were qualitatively similar to those observed at 12 days. However, at 40 days after ADM injection there was a statistically significant decrease in the axonal conduction velocity of the ADM MNs. 4. The normal correlations that are present between the AHP duration and electrical properties of the control motoneurons were observed in the ADM MNs, e.g., AHP duration was positively correlated with the input resistance and time constant and negatively correlated with the axonal conduction velocity. The correlation coefficients, however, were reduced in comparison with the control data. 5. This study demonstrates that ADM exerts significant effects on the electrical properties of motoneurons when injected into their target muscles. The majority of the changes in motoneuron electrical properties caused by ADM resemble those observed in motoneurons of aged cats. Additional research is required to determine whether the specific changes induced in motoneurons by ADM and those that occur in motoneurons in old age are due to similar degradative mechanisms.

Action Potentials↗
PubMed2001

Involvement of spinal NK2 and NMDA receptors in aversive behavior induced by intra-arterial injection of capsaicin.

The spinal processing by which intra-arterial injection of capsaicin (CAP) induces vocalization response (VOR) was investigated in guinea pigs. Intrathecal pre-treatment with CP-96,345 (a selective NK(1) receptor antagonist, 50 nmol) did not affect the CAP-induced VOR. However, significant attenuation of the VOR was observed by intrathecal pre-treatment with a selective NK(2) receptor antagonist MEN-10,376 (40 nmol) accompanied with a significant change in the response modality. MK-801 [an N-methyl-D-aspartate (NMDA) receptor antagonist, 20 and 40 nmol] inhibited the CAP-induced VOR dose-dependently without affecting the response modalities. Furthermore, intrathecal co-treatment with 40-nmol MEN-10,376 and 40-nmol MK-801 resulted in a marked inhibitory effect on the VOR followed by a significant alteration of response modalities. Intrathecal pre-treatment with neurokinin A (NKA; a tachykinin NK(2) receptor agonist, 1 nmol) enhanced the CAP-induced VOR. These behavioral results suggested that spinal NK(2) and NMDA receptors might have priority over NK(1) receptors in the spinal processing of nociceptive information from the CAP-sensitive nociceptor.

Animals↗
PubMed1984

The transience of cerebrocerebellar projections is due to selective elimination of axon collaterals and not neuronal death.

Fluorescent dyes were used to determine firstly if the transience of cerebrocerebellar projections in neonatal kittens is due to the selective elimination of axon collaterals or to neuronal death; and secondly, if the cerebrocerebellar projection neurons lived, did any maintain a projection to the brainstem or spinal cord. Injections of Fast Blue were made into the cerebellar cortex and deep nuclei in 7-9 postnatal days old kittens, the age in which cortical axons grow into the cerebellum. Later, at 31-71 postnatal days of age, when the transient cerebrocerebellar projections have disappeared, injections of Nuclear Yellow were made into the brainstem or the spinal cord. In the frontoparietal cortex, numerous neurons were labeled with Fast Blue suggesting that the disappearance of cerebrocerebellar projections is due primarily to the selective elimination of axon collaterals and not neuronal death. Moreover, many of the cortical neurons labeled with Fast Blue also were labeled with Nuclear Yellow which shows that many of the cortical neurons with transient collateral projections to the cerebellum in the neonate maintain a projection to brainstem or spinal targets in older animals.

Animals↗
PubMed2001

Antinociceptive effects after intrathecal administration of phosphodiester-, 2'-O-allyl-, and C-5-propyne-modified antisense oligodeoxynucleotides targeting the NMDAR1 subunit in mouse.

In the present study, we have compared the antinociceptive effect of three different types of antisense oligodeoxynucleotides targeting the N-methyl-D-aspartate (NMDA) R1-subunit in mice. The probes were administrated intrathecally three times during a period of 5 days (1, 5 or 25 microg/injection), followed by evaluation using the formalin test. The antinociceptive effect was correlated to in vitro receptor binding in spinal cord sections. The tissue distribution was studied after a single injection of fluorescein-conjugated probes. The phosphodiester probe showed superficial tissue penetration after 30 min and disappeared within 2 h. The probe did, however, significantly reduce both receptor binding in laminae I and II (by 36-44% compared to saline) as well as pain behavior (32% compared to saline), without apparent side effects. The mismatched probe was ineffective at 25 microg, while some reductions in receptor binding and pain behavior were seen after 5 microg. The C-5-propyne-modified phosphorothioate probe showed pronounced tissue penetration and cellular uptake as soon as 30 min after injection which was still detectable after 24 h. Immediately after injection of the highest dose, long-lasting hind-limb paralysis was observed. Receptor binding was reduced but not in a dose-related manner. Pain behavior was significantly reduced by 40% following 25 microg of antisense probe but not after lower doses or 25 microg of mismatched probe. The 2'-O-allyl-modified probe did not significantly reduce receptor binding or pain behavior. Thus, only the phosphodiester probe showed a significant correlation between reduction in pain behavior and receptor binding. These findings demonstrate that antisense technology is associated with specificity problems, but still could provide a valuable tool to study the role of different target proteins in the drug discovery process.

2-Amino-5-phosphonovalerate↗