Biomedical subjects

A J Beitz

Publications and source records attributed to A J Beitz.

At least 19 recordsLinked to original sources

PubMed1996

Spinal cord NMDA receptors modulate peripheral immune responses and spinal cord c-fos expression after immune challenge in rats subjected to unilateral mononeuropathy.

To characterize further the neural involvement in local immune reactions, we evaluated the effect of intrathecal NMDA-receptor blocker dizocilpine maleate (MK-801) on the peripheral immune response itself and on spinal cord c-fos expression induced by the delayed-type hypersensitivity (DTH) response. Immune challenge took place in the hind paw ipsilateral or contralateral to an injured sciatic nerve in both previously sensitized and immune-naive animals. An enhanced immune response was observed bilaterally in the hind paws of animals subjected to unilateral mononeuropathy compared with sham-operated controls. In contrast, no such enhancement was observed when neuropathic animals were challenged in the front paws. The increased DTH response was blocked successfully by the intrathecal administration of an analgesic dose of MK-801. Compared with sham-operated animals, animals subjected to unilateral mononeuropathy showed both a differential distribution and an increase in the number of c-fos-labeled neurons in the dorsal horn of the L3-L5 spinal cord segments after immune challenge. This was observed irrespective of whether the challenge took place ipsilateral or contralateral to the injured nerve. In addition to reversing the changes in immune response, intrathecal administration of MK-801 reversed the pattern of c-fos immunoreactivity in the spinal cord after immune challenge in neuropathic animals. These data suggest that select groups of spinal cord neurons participate in enhancing the peripheral immune response to a specific antigen in neuropathic animals and that this enhancement involves central NMDA receptors.

Animals↗

PubMed1995

Electrical stimulation of the sciatic nerve alters neuropeptide content and lymphocyte migration in the subcutaneous tissue of the rat hind paw.

To study the possible mechanism by which peripheral nerves mediate immune responses in target tissues, electrical stimulation of the sciatic nerve was combined with subcutaneous microdialysis of the hind paw. Following unilateral stimulation of the sciatic nerve, an ipsilateral rise in substance P and a bilateral rise in VIP levels were observed in dialysate samples from experimental vs control animals. Electrical stimulation of the sciatic nerve induced a marked hyperemia and swelling of the ipsilateral paw. Quantitative immunocytochemical analysis of paraffin-embedded sections of the hind foot pads demonstrated T lymphocyte migration ipsilateral to the stimulated nerve. These findings suggest that peripheral nerves can directly modulate local immune and inflammatory responses.

Animals↗

PubMed1995

Basal release of Met-enkephalin and neurotensin in the ventrolateral periaqueductal gray matter of the rat: a microdialysis study of antinociceptive circuits.

The periaqueductal gray (PAG) contains neural circuits that participate in descending antinociception. Anatomical and electrophysiological evidence suggests that these circuits might employ opioid peptides and GABA in series to remove a tonic inhibition of descending PAG output neurons. The present studies examined the release of the antinociceptive peptides Met-enkephalin and neurotensin in the ventrolateral PAG, and investigated the interaction between GABA and Met-enkephalin release. In awake and freely moving rats the ventrolateral PAG was dialysed using 25 ga. concentric probes. Basal release of peptide in 12 min or 40 min fractions was determined using radioimmunoassays. To establish how the ventrolateral PAG responds to nociception, dialysis was performed following unilateral hindpaw inflammation using Complete Freund's Adjuvant. Twenty-four hours after inflammation was induced, neurotensin release was increased 133% and Met-enkephalin release was increased 353% compared to control animals. Seven days after inflammation was induced, neurotensin release declined precipitously, while basal Met-enkephalin release remained elevated 313% above controls. Thus, unlike enkephalin, increased basal neurotensin release is not sustained with persistent tonic nociception. In addition, we confirmed in normal animals that the ventrolateral PAG is induced to release Met-enkephalin by systemic morphine. A 43% increase in basal Met-enkephalin release was observed immediately following a 12 mg/kg i.p. morphine injection. Morphine should have the opposite effect (inhibit peptide release) if it acts directly on the enkephalinergic neurons. Thus, we examined the hypothesis that GABAergic interneurons in the PAG mediated morphine-stimulated enkephalin release. When the GABAantagonist bicuculline (0.25 microM to 25 microM) was co-infused with the dialysis medium, Met-enkephalin release increased in a dose-dependent fashion and peaked 68% above pre-infusion levels. These data elucidate the reciprocal inhibitory relationship between GABA and enkephalin in the ventrolateral PAG. We hypothesize that, when nociception induces Met-enkephalin release within this region, the tonic GABAergic inhibition is overcome, resulting in greater sensitivity of PAG enkephalinergic neurons. Ultimately, this enhanced enkephalin release should result in greater excitability of the descending PAG output neurons that are responsible for antinociception.

Animals↗

PubMed1995

NMDA R1 mRNA distribution in motor and thalamic-projecting sensory neurons in the rat spinal cord and brain stem.

The N-methyl-D-aspartate (NMDA) receptor is important in both sensory and motor neurotransmission. In this study we examine NMDA R1 mRNA hybridization signal over individual sensory and motor neurons in the spinal cord and brain stem. A significantly greater quantity of NMDA R1 mRNA was present in motor neurons of the lumbar spinal cord and hypoglossal nucleus compared to thalamic projecting sensory neurons in the spinal cord dorsal horn, the spinal trigeminal nucleus pars caudalis and the cuneate and gracile nuclei. No significant difference in the quantity of NMDA R1 mRNA was observed between sensory neurons known to relay predominantly nociceptive information (trigeminothalamic and spinothalamic tract neurons) and that relay predominantly touch and proprioceptive information (dorsal column neurons).

Animals↗

PubMed1995

Castration increases [125I]MK801 binding in the hippocampus of male rats.

This study examines the effect of castration and androgen replacement on [125I]MK801 binding in the hippocampus. In castrated male rats, [125I]MK801 binding was significantly increased in both the stratum oriens and radiatum and the pyramidal cell layer of CA1. In contrast, no increase in [125I]MK801 binding was observed in the stratum oriens and radiatum of CA1 of castrated rats that were treated with dihydrotestosterone. No change in [125I]MK801 binding was observed in the CA3 region or dentate gyrus after castration. The observed increase in [125I]MK801 binding in pyramidal cell neurons within CA1 suggests that androgens may potentially affect hippocampal function by modulating pyramidal cell NMDA receptors.

Androgens↗

PubMed1995

Distribution of NMDAR1 receptor subunit mRNA and [125I]MK-801 binding in the hypothalamus of intact, castrate and castrate-DHTP treated male rats.

This study examines NMDAR1 receptor subunit mRNA expression and [125I]MK-801 binding in hypothalamic and limbic nuclei of intact, castrate and castrate-dihydrotestosterone propionate (DHTP)-treated male rats. In intact rats, the highest levels of NMDAR1 mRNA were observed in the supraoptic, suprachiasmatic, ventromedial and arcuate nuclei. Low levels of hybridization were observed in the bed nucleus of the stria terminalis, lateral preoptic area, lateral hypothalamic area and lateral septum. In castrated rats both NMDAR1 mRNA and [125I]MK-801 binding are significantly decreased in the lateral septum compared to castrate rats treated with DHTP, a non-aromatizable androgen. NMDAR1 mRNA was also significantly decreased in the supraoptic nucleus of castrate rats when compared to castrate rats treated with DHTP. These data suggest that androgens may modulate NMDA receptor function in some parts of the central nervous system.

Animals↗

PubMed1995

N-methyl-D-aspartate R1 messenger RNA and [125I]MK-801 binding decrease in rat spinal cord after unilateral hind paw inflammation.

Recent evidence suggests that N-methyl-D-aspartate receptors play an important role in the etiology and maintenance of chronic nociception. Previous studies have demonstrated that tissue injury or stimulation of nociceptive afferent projections results in the expansion of receptive fields, hyperalgesia and C-fiber-induced wind-up, events that can be inhibited by N-methyl-D-aspartate antagonists. This study examines the effect of unilateral hind paw inflammation on N-methyl-D-aspartate R1 messenger RNA and [125I]dizocilpine maleate binding in the L4-L5 segments of the lumbar spinal cord of rats. Spinal cords were examined at 7.5 h, three, seven and 20 days after injection of the left hind paw with 120 microliters of complete Freund's adjuvant. N-methyl-D-aspartate R1 messenger RNA, as measured with in situ hybridization, was observed to decrease bilaterally in laminae I, II and X of the lumbar spinal cord. This decrease was evident in laminae I and II at 7.5 h and three days after hind paw injection. In lamina X, a postinjection decrease in hybridization signal was observed at 7.5 h and seven days. A bilateral decrease in [125I]dizocilpine maleate binding was observed in laminae I and II at three, seven and 20 days after paw injection. This observed decrease in binding at the N-methyl-D-aspartate receptor suggests a compensatory mechanism by which N-methyl-D-aspartate-mediated nociceptive events may be modulated.

Animals↗

PubMed1994

Immunocytochemical evidence that quisqualate is selectively internalized into a subset of hippocampal neurons.

Quisqualic acid (QUIS) has been shown to interact with several glutamate receptor subtypes and uptake sites. We have previously demonstrated that a brief exposure of hippocampal cells to QUIS sensitizes them to depolarization by the alpha-amino-omega-phosphonate analogues of glutamate, AP4, AP5, and AP6. This QUIS-induced sensitization is accompanied by the active uptake of QUIS into hippocampal slices. In order to localize the sites of QUIS uptake into rat hippocampal slices, a polyclonal antibody against QUIS was raised in rabbits. Utilizing immunocytochemical techniques, we have identified immunoreactive axons and dendrites after brief exposure times to QUIS, and perikarya after longer exposure times to QUIS. The intensity of the QUIS immunoreactivity increased as the exposure time to QUIS increased. QUIS immunoreactivity was primarily found in stratum oriens and stratum radiatum, of regions CA1, CA2, and CA3 of the hippocampus as well as in the hilus and molecular layer of the dentate gyrus. The distribution and morphology of QUIS immunoreactive cells appeared to be similar to those of GABAergic interneurons. Glial fibrillary acidic protein (GFAP) did not co-localize with the QUIS-internalizing cells suggesting that they are not glia. Ultrastructural analysis revealed QUIS immunoreactive profiles within the stratum radiatum. Immunostained profiles at both the light and EM levels appeared, in many cases, to be swollen and showed signs of degeneration. Such changes were only evident in tissue exposed to QUIS. These data demonstrate that QUIS is taken up by a select group of neurons in the rat hippocampus.

Animals↗

PubMed1994

Differential NMDA NR1 mRNA expression among spinal trigeminal neurons that project to different targets.

The N-methyl-D-aspartate (NMDA) NR1 glutamate receptor subtype has been proposed to play an important role in the transmission of orofacial sensory information in the spinal trigeminal nucleus (STN). The distribution of NR1 mRNA expression in the STN and its relationship to STN projection neurons has not been investigated previously. Using neuroanatomical tract tracing with in situ hybridization techniques, we found that neurons in the STN that project to the thalamus, cerebellum and spinal cord expressed more mRNA for NR1 than do nonprojection neurons. Trigeminothalamic neurons were found to express more NR1 mRNA than trigeminospinal or trigeminocerebellar neurons. Thus, NMDA-specific excitatory amino acids may be more efficacious in the relay of orofacial information to the thalamus than to the spinal cord or cerebellum.

Animals↗

PubMed1994

Distribution of nitric oxide synthase-immunoreactive interneurons in the spinal trigeminal nucleus.

The spinal trigeminal nucleus is involved in the transmission of orofacial sensory information. Neither the distribution of the neuromessenger, nitric oxide, within the trigeminal system nor the possible relationship of this simple gas with trigeminothalamic neurons has been carefully studied. Using immunocytochemical (against nitric oxide synthase) and histochemical (NADPH-diaphorase staining) techniques, we have found that nitric oxide neurons and processes are more prominent in the nucleus caudalis and the dorsomedial aspect of the nucleus oralis than in other spinal trigeminal regions. To study the relationship of nitric oxide to trigeminothalamic neurons and intertrigeminal interneurons of the spinal trigeminal nucleus, spinal trigeminal neurons were retrogradely labeled with fluorogold by thalamic injections or by injections into the junction of the nucleus interpolaris and nucleus caudalis. Medullary sections were subsequently processed with NADPH-diaphorase histochemistry. None of the diaphorase-stained neurons in the spinal trigeminal nucleus was found to contain fluorogold; however, some diaphorase-stained processes were found in close proximity to trigeminothalamic neurons. Following spinal trigeminal nucleus injections, many diaphorase-stained neurons were found to contain fluorogold, especially in the nucleus caudalis, suggesting that nitric oxide-containing neurons in the spinal trigeminal nucleus are intertrigeminal interneurons. Collectively, these data indicate that nitric oxide is most prominent in interneurons located in nucleus caudalis and that these interneurons give rise to processes that appose trigeminothalamic neurons, raising the possibility that they may indirectly influence orofacial nociceptive processing at the level of the spinal trigeminal nucleus via nitric oxide production.

Amino Acid Oxidoreductases↗

PubMed1994

NMDA receptor mRNA expression in NOS-containing neurons in the spinal trigeminal nucleus of the rat.

The spinal trigeminal nucleus (STN) is involved in the transmission of orofacial sensory information. Nitric oxide (NO), an important neuromessenger, and the glutamate receptor subtype, NMDA NR1, have been implicated in nociception in the STN. However, the anatomical relationship of NO and NMDA NR1 has not been investigated within this nucleus. Using both immunocytochemical (against NO synthase; NOS) and in situ hybridization studies of NMDA NR1 receptor mRNA, we found that NOS-containing neurons in the STN expressed more mRNA for NR1 than did non-NOS-containing neurons in the STN. These data suggest that NMDA activation may lead to NO production in the STN and is consistent with previous studies, implicating both NMDA and NO in nociception.

Amino Acid Oxidoreductases↗

PubMed1994

Characterization of the effect of cholecystokinin (CCK) on neurons in the periaqueductal gray of the rat: immunocytochemical and in vivo and in vitro electrophysiological studies.

The periaqueductal gray (PAG) is an important integration site for pain, autonomic functions, vocalization, fear and anxiety. Cholecystokinin (CCK) is a major neurotransmitter in the PAG and CCK receptors are heterogeneously distributed within the PAG. Since CCK antagonists are anxiolytic and potentiate morphine analgesia, it is possible that these effects of CCK are mediated through alteration of neuronal activities in the PAG. The goals of this study were to examine the anatomical and physiological properties of the PAG CCK containing systems. The distribution of CCK-containing axons and boutons in PAG was examined using immunohistochemical procedures. These studies show that CCK-like immunoreactive (CCK-LIR) fibers and terminals are present throughout PAG, but are particularly heavily concentrated in a focal column that runs longitudinally throughout the rostrocaudal axis of dorsolateral PAG and in nucleus cuneiformis which represents a caudolateral extension of PAG. The physiological effects of CCK on PAG neurons were examined in both in vivo and in vitro preparations. In the in vivo experiments multibarreled electrodes were used to record from PAG neurons and to apply CCK and the CCK antagonists, CR1409 and proglumide. Of 37 neurons recorded in vivo, CCK caused excitation in 25 cells, inhibited 7 cells and had no effect on 5 cells. The excitatory effect was blocked by CR1409 in 11/11 cells tested. Proglumide blocked the excitatory response of CCK in 12/14 cells. Proglumide blocked the inhibitory effect in 2 of 7 cells, but CR1409 had no effect on CCK-evoked inhibition in 7 cells tested. Extracellular, conventional intracellular and whole cell patch clamping procedures were used to study CCK actions in the in vitro slice preparation. In the extracellular recording experiments, responses of PAG cells to CCK were measured in slices that were maintained at 22 degrees C (room temperature) and at 32 degrees C. CCK excited 40/56, inhibited 7/56 and had no effect on 9/56 cells; excitatory responses were blocked by CR1409 in 32/36 cells and by proglumide in 25/27 cells tested. Inhibitory responses to CCK were unaffected by CR1409, but were blocked in 3/7 cells by proglumide. Conventional intracellular recordings were made from 13 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Cerebellar injury induces NOS in Purkinje cells and cerebellar afferent neurons.

Purkinje cells of the cerebellar cortex and neurons of most precerebellar nuclei are conspicuous by the absence of constitutive (neuronal) nitrix oxide synthase (nNOS). Here we show that following mechanical, chemical or thermal injury to the cerebellar cortex there is an induction of nNOS in Purkinje cells as identified with NADPH-diaphorase (NADPH-d) histochemistry and nNOS immunocytochemistry. Induced nNOS and NADPH-d (inNOS/NADPH-d) first appeared 72 hours post-treatment and persisted in excess of 8 weeks. Precerebellar neurons throughout the brain stem also exhibited induced nNOS and NADPH-d with a similar time course. These results indicate that brain lesions can induce nNOS in local neurons and in neurons which are afferent to the leasioned area.

Amino Acid Oxidoreductases↗

PubMed1994

Hemilabyrinthectomy causes both an increase and a decrease in corticotropin releasing factor mRNA in rat inferior olive.

It was previously shown [NeuroReport, 3 (1992) 829-832] that unilateral labyrinthectomy (UL) induces Fos expression in several brainstem regions, including the beta subnucleus of the inferior olive. Using isotopic 33P in situ hybridization, the present results demonstrate significant changes in oligonucleotide-probed mRNA levels for corticotropin-releasing factor (CRF) in the rat inferior olivary nucleus 4 days following unilateral labyrinthectomy (UL). In the medulla of normal animals there was strong CRF mRNA labeling in the inferior olivary nucleus, and weaker labeling in the vestibular nuclei and prepositus hypoglossi. Following unilateral labyrinthectomy, the contralateral olivary beta subnucleus showed a significant increase in CRF message, similar to the contralateral Fos labeling observed after hemilabyrinthectomy [NeuroReport, 3 (1992) 829-832]. In addition, the contralateral A and B subnuclei (IOA/B) of the inferior olive showed a strong increase in CRF labeling, while the ipsilateral dorsal cap of Kooy (IOK) showed a decrease. This novel bidirectional alteration in CRF message in different subdivisions of the same nuclear group indicates the existence of both up and down regulatory mechanisms controlling CRF peptide expression, and reflects the dynamic neurochemical alterations occurring during vestibular compensation.

Animals↗

PubMed1994

Chronic pain and immunity: mononeuropathy alters immune responses in rats.

In order to investigate the possible relationship between chronic pain and the immune system, delayed-type hypersensitivity (DTH) and humoral immunity were assessed in Sprague-Dawley rats subjected to unilateral peripheral mononeuropathy induced by sciatic ligation. Paw withdrawal latency (PWL) time was measured twice during the experiment in animals subjected to sciatic nerve ligation or sham surgery. Sciatic nerve-ligated animals showed hyperalgesia in the leg subjected to neural ligation when compared to the contralateral leg. No differences in PWL times existed in sham-operated animals. In order to exclude possible alterations in immune response due to the surgical procedure or to the hyperalgesia testing, a group of control animals, not subjected to surgical procedures or hyperalgesia testing, was also included in the experiment. Three days post-sciatic ligation or sham surgery, both experimental and control animals were sensitized to keyhole limpet hemocyanin (KLH). A secondary sensitization followed 1 week after the initial immunization. Fourteen days after the initial sensitization, KLH was injected into the hind foot pad and vehicle into the contralateral foot pad in order to assess DTH. One group of rats subjected to sciatic nerve ligation was tested for DTH in the hind foot pad ipsilateral to the ligated nerve, while another group was tested in the contralateral foot pad. Twenty-four hours following foot pad injections, the thickness of both paws was measured and animals were bled to test for anti-KLH immunoglobulins. Animals in which mononeuropathy was induced, but not sham-operated or control animals, exhibited an enhanced DTH response to KLH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Chronic pain increases brainstem proneurotensin/neuromedin-N mRNA expression: a hybridization-histochemical and immunohistochemical study using three different rat models for chronic nociception.

The role of neurotensin in the central nervous system is poorly understood. Exogenous neurotensin has potent antinociceptive effects when injected into the midbrain periaqueductal gray (PAG). Although it is present in terminals, fibers and perikarya within the PAG and other midbrain regions known for their antinociceptive circuits, it is not known whether endogenous neurotensin modulates nociception. We examined the midbrain in three different rat models for nociception to learn whether acute or chronic pain altered neuronal levels of the proneurotensin/neuromedin N mRNA (neurotensin mRNA). The models were: adjuvant-induced polyarthritis, adjuvant-induced unilateral paw inflammation, and unilateral peripheral mononeuropathy caused by ligation of the sciatic nerve. Behavioral observations confirmed that the expected symptoms developed as previously described. Within each of the three experimental models, we performed in situ hybridization histochemistry on coronal sections from three midbrain levels that included the rostral one-third of the PAG, the middle one-third of the PAG, and the caudal one-third of the PAG. At the level of the rostral PAG, we found that neither chronic nor acute nociception altered the frequencies or distributions of neurons containing neurotensin mRNA. In contrast, at the levels of the mid- and caudal one third of the PAG, the early effects of the nociceptive lesions differed from the chronic effects. During the acute phase of each model, increases in either the frequency or field area of neurons that were hybridization-positive for neurotensin mRNA were confined to the ventromedial PAG and the dorsal raphe nucleus. As the nociceptive stimuli became chronic, the early increases in neurotensin mRNA-containing neurons at the level of the middle third of the ventral PAG were diminished but remained above control levels, while increases in neurotensin mRNA began to occur in the midbrain tegmentum lateral to the PAG. The most striking increases in neurotensin mRNA expression were observed 16-17 days after the onset of nociceptive stimuli. At the level of the mid-PAG and caudal PAG, increased hybridization signal intensities and neuron frequencies occurred within the nucleus cuneiformis and the lateral tegmental nuclei, including the pedunculopontine and microcellular tegmental nuclei, as well as the deep mesencephalic nuclei. Hybridization-positive neurons in the tegmental nuclei were not observed at early stages of lesion development, but were a consistent feature of caudal midbrains after nociception became chronic.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Nitric oxide synthase immunoreactive neurons anatomically define a longitudinal dorsolateral column within the midbrain periaqueductal gray of the rat: analysis using laser confocal microscopy.

Nitric oxide has recently been proposed as a neuronal messenger in both the central and peripheral nervous system. Antibodies against nitric oxide synthase (NOS), the synthesizing enzyme for nitric oxide, were used in combination with immunocytochemistry and confocal laser microscopy to analyze the distribution of this enzyme in the midbrain periaqueductal gray (PAG) of the rat. NOS immunoreactive neurons were localized predominantly in a longitudinally oriented column in the dorsolateral PAG. NOS immunoreactive fibers and processes were scattered throughout the PAG but were most prevalent in the dorsolateral column and in the juxta-aqueductal column. This study provides neurochemical support for the existence of longitudinal columns in the PAG which are postulated to underlie the functional organization of this complex brainstem region.

Amino Acid Oxidoreductases↗

PubMed1993

Nitric oxide synthase is found in some spinothalamic neurons and in neuronal processes that appose spinal neurons that express Fos induced by noxious stimulation.

To determine if nitric oxide (NO) and Fos immunoreactivity induced by noxious stimulation were colocalized in spinothalamic neurons, double-staining immunocytochemical techniques were combined with retrograde neuroanatomical tracing procedures. Initial studies on three rats demonstrated that Fos and nitric oxide synthase (NOS), the synthesizing enzyme for nitric oxide, did not coexist in spinothalamic tract neurons. However, some spinothalamic neurons were found to contain NOS and some NOS immunoreactive processes were found to appose Fos containing neurons. Thus the remainder of the study: (1) analyzed the relationship of NOS positive neuronal processes with Fos stained neurons using a Fos immunocytochemical technique in combination with either NOS immunofluorescence or NADPH-diaphorase histochemistry; and (2) quantitated the number of NOS containing cells that project to the thalamus using a combined immunofluorescent-retrograde tracing procedure. Both NOS-like immunoreactive (NOS IR) neuronal processes and NADPH-diaphorase positive neuronal processes in the dorsal horn of the lumbar spinal cord were found to appose Fos positive neurons located in laminae I and II of the dorsal horn. Approximately 40% of Fos-labeled cells in these superficial laminae were found to be in apposition to or in close proximity to NOS labeled neuronal processes. Examination of spinal cord sections for NOS-containing spinothalamic tract neurons revealed that lamina X was the only spinal cord region containing such double-labeled neurons. Further quantification revealed that approximately 10% of NOS positive neurons in lamina X were double-labeled with Fluorogold. These findings support the hypothesis that nitric oxide is involved in nociceptive events occurring in the spinal cord in response to a peripheral noxious stimulus and further indicate that nitric oxide may contribute to the central transmission of spinothalamic information.

Amino Acid Oxidoreductases↗