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I Tavares

Publications and source records attributed to I Tavares.

At least 19 recordsLinked to original sources

Body composition assessed by impedance changes very early with declining renal graft function.

BACKGROUND: Kidney transplant (Tx) restores renal filtration, although it does not achieve the function of two native kidneys, and with time it may variably involute back to chronic renal failure. We hypothesized that bioelectrical impedance analysis (BIA) might highlight differences for body compartments among Tx with different filtration rates, and we compared them with healthy controls. METHODS: 38 Tx patients (25 males, 13 females) were studied at 75.9 +/- 37.8 months postsurgery and divided into three groups: good creatinine clearance (CrCl, ml/min/1.73 m2; > 65.0), borderline (35.0 < CrCl < 60.0) and bad (CrCl < 35.0). BIA was assessed three times in a year. Total body water, extracellular water (ECW), intracellular water (ICW), Na:K exchange rate (Nae:Ke) and phase angle were studied. Healthy (n = 11) and hemodialysis (n = 11) groups were also studied. RESULTS: BIA showed no differences between healthy controls and good Tx while both borderline and bad Tx presented a significantly higher ECW and lower ICW than either good Tx or normal controls. Only good CrCl was different from predialysis. CONCLUSIONS: A good kidney graft manages to restore and maintain normal body composition, even with potential disturbances brought about by steroids and cyclosporine. With mild renal dysfunction a change in body compartments was observed, moving towards the composition of that with chronic renal failure patients.

Adult↗

Secondary hyperalgesia in the monoarthritic rat is mediated by GABAB and NK1 receptors of spinal dorsal horn neurons: a behavior and c-fos study.

Secondary hyperalgesia in the monoarthritic rat is accompanied by a decrease in nociceptive activation of spinal neurons expressing GABA(B) receptors and by the opposite effect in the cells expressing neurokinin 1 (NK1)-receptors. In order to ascertain the relative role of each receptor, the effects of intrathecal administration of SP-saporin (SP-SAP), baclofen or both were evaluated, using a model of secondary hyperalgesia that consists of mechanical stimulation of the hindlimb skin close to an inflamed joint. Four days after the induction of monoarthritis by intraarticular injection of Complete Freund's Adjuvant (CFA), a cannula was implanted at T(13)-L(1) level and 10 microl of saline or SP-SAP (10(-6) M) were intrathecally (i.t.) injected. Fourteen days after CFA-injection, half of the animals from each group received i.t. injections of 10 microl saline and the remainder were injected with the same volume of baclofen (1 microg). Ten minutes later, the animals were behaviorally evaluated by the von Frey test or submitted to noxious mechanical stimulation to analyze c-fos expression. The von Frey thresholds increased after the treatments, but more pronouncedly after baclofen or SP-SAP plus baclofen. In segments L(2)-L(3), the spinal area that receives input from the stimulated skin close to the inflamed joint, the numbers of Fos-immunoreactive neurons were reduced after the three treatments both in the superficial and deep dorsal horn. In segments T(13)-L(1), the numbers of Fos-immunoreactive neurons were significantly reduced after treatment with SP-SAP plus baclofen in both dorsal horn regions, and in the deep dorsal horn after baclofen treatment. We conclude that both GABA(B) and NK1 receptors of spinal dorsal horn neurons participate in secondary hyperalgesia in the monoarthritic rat, although the decrease in GABA inhibition appears to play a more important role than the increase in SP-mediated effects.

Animals↗

Differential expression of NK1 and GABAB receptors in spinal neurones projecting to antinociceptive or pronociceptive medullary centres.

The balance between excitatory and inhibitory input exerted upon spinal cord neurones that belong to spinofugal pathways determines the ultimate type of information transmitted to the brain. We compared the relative expression of NK1 and GABAB receptors in two spinomedullary pathways targeting an antinociceptive area and a pronociceptive centre, respectively, the lateral part of the caudal ventrolateral medulla (VLMlat) and the dorsal reticular nucleus (DRt). Spinal cord sections of rats injected in the VLMlat or DRt with the retrograde tracer cholera toxin subunit B were triple-immunoreacted for the tracer, NK1 receptors and GABAB receptors. The dorsal horn neurones labelled from the VLMlat mainly co-localized the two receptors while those labelled from the DRt mainly expressed GABAB receptors, which was particularly evident in neurones of laminae IV-V. The morphological classification of lamina I neurones projecting to the VLMlat showed that fusiform, flattened and pyramidal cells mainly co-localized NK1 and GABAB receptors. As to lamina I neurones projecting to the DRt, multipolar neurones mainly expressed GABAB receptors while the majority of flattened and pyramidal neurones co-localized NK1 and GABAB receptors. The present results suggest that the expression of NK1 and GABAB receptors varies in neurones participating to different spinofugal pathways. The importance of the present findings in the knowledge of the endogenous supraspinal pain control system is discussed.

Animals↗

Imbalance between the expression of NK1 and GABAB receptors in nociceptive spinal neurons during secondary hyperalgesia: a c-Fos study in the monoarthritic rat.

The neurochemical changes that operate in nociceptive spinal cord circuits during secondary hyperalgesia are largely unknown, in particular with respect to the balance between excitatory and inhibitory neurotransmission. In this study we evaluated the expression of NK1 and GABA(B) receptors in nociceptive spinal neurons in a model of secondary hyperalgesia consisting of noxious mechanical stimulation of the hindlimb skin close to a joint chronically inflamed by complete Freund's adjuvant. In spinal segments receiving input from that skin area, Fos-immunodetection was combined with immunocytochemistry for NK1 receptors, GABA(B) receptors or both receptors. In control and monoarthritic animals, neurons double-labeled for Fos and each receptor occurred mainly in laminae I and IV-V. In lamina I, the percentage of NK1 neurons expressing Fos was higher in monoarthritics while lower percentages of GABA(B) neurons expressed Fos. The percentage of Fos-positive cells expressing NK1 immunoreaction did not change in monoarthritics but that of Fos cells with GABA(B) immunoreaction was lower in these animals. In laminae IV-V, a large increase in Fos expression was detected in monoarthritic rats but the relative proportions of Fos-positive neurons expressing each receptor were similar in the two groups. Co-localization of NK1 and GABA(B) receptors occurred only in lamina I neurons in both experimental groups with no differences between control and monoarthritic animals in the percentages of Fos-positive neurons that expressed the receptors. Considering the participation of lamina I neurons bearing NK1 and GABA(B) receptors in several spinofugal systems, it is possible that the imbalance between excitatory and inhibitory actions exerted, respectively, by substance P and GABA may subserve secondary hyperalgesia by increasing ascending transmission of nociceptive input.

Animals↗

Brain afferents to the lateral caudal ventrolateral medulla: a retrograde and anterograde tracing study in the rat.

The ventrolateral medulla (VLM) modulates autonomic functions, motor reactions and pain responses. The lateralmost part of the caudal VLM (VLMlat) was recently shown to be the VLM area responsible for pain modulation. In the present study, the brain sources of VLMlat afferent fibers were determined by tract-tracing techniques. Following injection of cholera toxin subunit B into the VLMlat, retrogradely labeled neurons in the forebrain occurred at the somatosensory, insular, motor, limbic and infralimbic cortices, and at the central amygdaloid nucleus. Retrogradely labeled neurons in diencephalic regions were observed in the lateral hypothalamus, posterior hypothalamus and paraventricular nucleus. In the brainstem, retrograde labeling occurred at the periaqueductal gray, red nucleus, parabrachial area, nucleus raphe magnus, nucleus tractus solitarii, lateral reticular nucleus and dorsal and ventral medullary reticular formation. In the cerebellum, retrogradely labeled neurons occurred at the lateral nucleus. Following injections of the anterograde tracer biotinylated dextran amine (BDA) into the lateral hypothalamus or paraventricular nucleus, anterogradely labeled fibers were mainly observed in the VLMlat. Injections of BDA into the periaqueductal gray, red nucleus or lateral nucleus of the cerebellum resulted in anterograde labeling in the VLMlat and lateral reticular nucleus. The present study gives an account of the brain regions putatively involved in triggering the modulatory actions elicited from the VLMlat. These include areas committed to somatosensory processing, autonomic control, somatic and visceral motor activity and affective reactions. The findings suggest that the VLMlat may play a major homeostatic role in the integration of nociception with other brain functions.

Adjuvants, Immunologic↗

Projection sites of superficial and deep spinal dorsal horn cells in the nucleus tractus solitarii of the rat.

By using anterograde transport of biotin dextran amine injected into the cervical spinal dorsal horn, we have shown that fibres from superficial and deep dorsal horn project to the nucleus tractus solitarii via two distinct pathways. Afferent fibres from the superficial lamina (I-III) were found to course in the dorsal funiculus and terminate bilaterally in the caudal zone of the nucleus tractus solitarii (NTS), mainly within the commissural subnucleus. In contrast, afferents from the deeper dorsal horn laminae (IV-V) were found to course in the dorsolateral fasciculus and terminate ipsilaterally, mostly in the lateral areas of the caudal nucleus tractus solitarii. Similar, but more extensive patterns of labelled fibres were produced by injections into the white matter of the dorsal funiculus and dorsolateral fasciculus, respectively. These observations suggest that the caudal NTS not only serves as a location of visceral afferent convergence and integration, but may also be a receptive area for monosynaptic projections from dorsal horn neurons receiving sensory afferent inputs. Such projections may represent pathways through which NTS neurons are influenced by nociceptive and non-nociceptive information from the dorsal horn and thereby can co-ordinate the appropriate autonomic response, including adjustments in cardiorespiratory reflex output.

Afferent Pathways↗

Reciprocal connections between the medullary dorsal reticular nucleus and the spinal dorsal horn in the rat.

The synaptic architecture of spinal afferents of the dorsal portion (DRtd) of the medullary dorsal reticular nucleus (DRt) is studied. After iontophoretic injections of cholera toxin subunit B (CTb) into the superficial (laminae I-II), deep (laminae IV-V) or entire (laminae I-V) dorso-ventral extent of the spinal dorsal horn at the cervico-thoracic or lumbo-sacral levels, axonal boutons of two distinct types were labelled in the DRtd. Type A boutons (82% after cervico-thoracic injections and 92% after lumbo-sacral injections) were roundish, small and presented few mitochondria and small, round synaptic vesicles. Type B boutons (18% after cervico-thoracic injections and 8% after lumbo-sacral injections) were elongated, two to three times larger, and exhibited numerous mitochondria and larger round vesicles. Both types of bouton established asymmetrical synaptic contacts with small dendritic profiles and, less frequently, with dendritic trunks and perikarya. Retrograde labelling occurred in the postsynaptic profile of 15-18% type A boutons labelled from any injection site. Taken together with previous data on DRt-spinal synaptic contacts at the superficial dorsal horn, the present results point to the occurrence of a reciprocal excitatory loop connecting the dorsal DRt and lamina I, which may be at the basis of the DRt-mediated pain-facilitating effects described recently.

Afferent Pathways↗

Comparison of indomethacin and nimesulide, a selective cyclooxygenase-2 inhibitor, on key pathophysiologic steps in the pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in the rat.

BACKGROUND: The predicted gastrointestinal tolerability of specific cyclooxygenase-2 inhibitors could be due to either a lack of 'topical' irritation and/or lack of effect on cyclooxygenase-1. METHODS: Key pathophysiologic steps (in vitro and in vivo uncoupling, intestinal prostanoid levels (prostaglandin E, thromboxane B2, and 6-keto-prostaglandin F1alpha), intestinal permeability (51Cr-ethylenediaminetetraacetic acid), inflammation (faecal excretion of a granulocyte marker protein), and ulcer counts) in enteropathy induced by nonsteroidal anti-inflammatory drugs were assessed after administration of indomethacin, 10 mg/kg, and 15 (roughly equipotent), 30, and 60 mg/kg of the preferential cyclooxygenase-2 inhibitor nimesulide. RESULTS: Indomethacin uncoupled oxidative phosphorylation at lower concentrations than nimesulide in vitro. Indomethacin was associated with electron microscopy changes suggestive of uncoupling in 60%-70% of enterocytes examined, whereas nimesulide affected 10%-30% of enterocytes, depending on the dose. Indomethacin increased intestinal permeability and caused inflammation and ulcers with 71%-96% reductions in prostanoid levels. Nimesulide at 15 mg/kg caused no damage, whereas 30 and 60 mg/kg nimesulide were associated with significant decreases in mucosal prostanoids (46%-75%), but only the 60-mg/kg dose caused a transient increase in intestinal permeability. However, at none of the doses did nimesulide cause intestinal inflammation or ulcers. CONCLUSIONS: These results endorse the idea that selective cyclooxygenase-2 inhibitors may be associated with some gastrointestinal tolerance due to their selectivity for cyclooxygenase-2, inhibiting cyclooxygenase-1 at only very high doses, and reduced topical irritation.

Animals↗

Lesions of the caudal ventrolateral medulla block the hypertension-induced inhibition of noxious-evoked c-fos expression in the rat spinal cord.

The effect of lesioning the lateral portion of the caudal ventrolateral medullary reticular formation (VLMIat) on the noxious-evoked expression of the c-fos proto-oncogene in spinal neurons, was studied in short-term hypertensive rats. Occlusion of the renal artery for 96 h in unlesioned animals induced a 52% increase in blood pressure (BP) and a 66% decrease in the number of Fos-immunoreactive (Fos-IR) spinal cells following noxious cutaneous stimulation, as compared to values in normotensive controls. Lesioning the VLMIat in hypertensive rats by unilateral quinolinic acid (QA) injection (0.3 microl of a 180 nmol/microl solution) 24 h before noxious stimulation, prevented the Fos-IR cell decrease. In normotensive rats, lesioning the VLMIat produced no changes in c-fos expression. To investigate the role played by the VLMIat in cardiovascular control, BP and heart rate (HR) were measured during local injections of QA or glutamate (0.5 microl of a 100 nmol/microl solution) to normotensive animals. Injections of QA produced an immediate rise in BP and HR which reached maximal values (18 and 14% increase, respectively) 5 min after the administration onset, then returning gradually to baseline levels. Glutamate injections resulted in an immediate decrease of the same values, which reached 29 and 39%, respectively, 4 min after the beginning of injection, after which they decreased to baseline levels. These results suggest that VLMIat neurons inhibit nociceptive spinal neurons in response to rises in blood pressure, while exerting negative control of cardiovascular parameters. It is suggested that the VLMIat is involved in the genesis of hypoalgesia during hypertension.

Journal Article↗

The pontine A5 noradrenergic cells which project to the spinal cord dorsal horn are reciprocally connected with the caudal ventrolateral medulla in the rat.

A disynaptic pathway linking the caudal ventrolateral medulla (VLM) to the spinal cord via the A5 noradrenergic cell group of the pons has recently been described in the rat. In the present work, the projections of the A5 to the VLM and to the spinal dorsal horn were studied with double-tracing techniques combined with immunostaining of the noradrenaline-synthesizing enzyme dopamine-beta-hydroxylase. Cholera toxin subunit B (CTb) injected into the VLM and fluoro-gold injected into the spinal dorsal horn produced double retrograde labelling of A5 neurons immunoreactive for dopamine-beta-hydroxylase, which received appositions of fibre varicosities labelled anterogradely with CTb injected into the VLM. After injecting CTb into the A5, retrogradely labelled neurons occurred in the VLM. These neurons were contacted by anterogradely labelled fibres from the A5 group. These observations indicate that the VLM cells acting upon the A5 spinally projecting neurons, which are likely to exert an alpha2-adrenoreceptor-mediated inhibition on the spinal cord, are targeted by collaterals of the A5 spinal cord-bound axons. The A5-VLM pathway may be the anatomical substrate of a negative feedback circuit whereby the modulatory action of the VLM on the spinal cord is self-inhibited through activation of the A5.

Animals↗

The ventrolateral medulla of the rat is connected with the spinal cord dorsal horn by an indirect descending pathway relayed in the A5 noradrenergic cell group.

The pathway conveying the descending inhibitory noradrenergic input elicited from the caudal ventrolateral medulla (VLM) onto the spinal cord dorsal horn was studied in the rat. Retrograde labeling with cholera toxin subunit B (CTb) injected into the dorsal horn was combined with immunostaining for dopamine-beta-hydroxylase (DBH) in the VLM and other brainstem nuclei containing noradrenergic cells. CTb-labeled neurons occurred in the lateral part of the VLM (VLMlat), located ventrolaterally to the DBH-immunoreactive cells of the A1 noradrenergic cell group. Neuronal profiles stained for CTb and DBH (double labeled) occurred in the A5 (31%), A6 (57%), and A7 (12%) noradrenergic cell groups. To ascertain whether noradrenergic cells targeting the spinal cord in those groups received projections from the VLMlat, this area was injected with the anterograde tracer biotinylated dextran amine (BDA). Labeled terminal fibers with boutons en passant were apposed to numerous double-stained neurons in the A5 cell group. Similar appositions occurred in small amounts in the ventral subcoerulear component of the A6. Correlated light and electron microscopic analyses of the labeled appositions revealed that the BDA-labeled axonal boutons contained spherical vesicles and were presynaptic at asymmetrical contacts to somata and dendritic profiles of the double-stained A5 neurons. These data indicate the occurrence of an indirect dysynaptic pathway connecting the VLM to the spinal cord, with a relay in the A5 cells. This pathway may convey the antinociceptive effects mediated by alpha 2-adrenoreceptors, which have been previously observed in the spinal cord following VLM stimulation.

Animals↗

Hypertension inhibits noxious-evoked c-fos expression in the rat spinal cord.

The effect of hypertension on spinal induction of the c-fos proto-oncogene following noxious mechanical stimulation of the skin was studied in the rat. The occlusion of renal artery raised blood pressure steeply, reaching 52% over initial values. Oral administration of NG-nitro-L-arginine methyl ester provoked a gradual increase in blood pressure which reached up to 62%. The numbers of spinal dorsal horn Fos-immunoreactive nuclei were reduced to 66% and 38% of controls in animals with renal- and pharmacologically-induced hypertension, respectively. These data indicate that hypertension is accompanied by an inhibition of spinal nociceptive neurones which probably accounts for the hypoalgesia observed in hypertensive subjects. They further suggest an influence by the rate of increase of blood pressure on the level of spinal inhibition.

Animals↗

Projection sites of superficial or deep dorsal horn in the dorsal reticular nucleus.

The termination sites in the medullary dorsal reticular nucleus (DRt) of axons arising from superficial or deep dorsal horn cells were analysed by anterograde tracing with biotinylated dextran (BD). Following BD injections in spinal laminae I-III or in these laminae plus the dorsal funiculus, labelled fibres and boutons were located in the dorsal most ipsilateral portion of the DRt. Injections covering laminae III-V or laminae I-V resulted in bilateral labelling of the ventral DRt and ipsilateral labelling of the dorsal DRt. These findings, together with previous data concerning the origin of DRt projections to the superficial or deep dorsal horn, suggest the occurrence of reciprocal anatomical loops connecting the dorsal or the ventral areas of both regions.

Animals↗

[The assessment of functional status in the elderly. The application of a Portuguese version of the COOP/WONCA charts].

INTRODUCTION: The outcomes of medical care can be measured in terms of health or functional status. Several outcomes measures have been developed in the last years but, there are several difficulties with cross-cultural adaptations. This study is mainly an application exercise to a group of old people of a Portuguese version of the COOP/WONCA charts. METHODS: A descriptive cross-sectional study with a component of qualitative analysis was done. Population basis was the elderly registered in the lists of five family doctors in two Portuguese health centres (Lumiar and Costa da Caparica) in the Lisbon region. A random sample of 189 patients (aged 65 and over) was interviewed. The studied variables were: gender, age, civil status, literacy, co-morbidity and dimensions of the COOP/WONCA charts. Univariate and bivariate analysis was done. A qualitative analysis was also performed to approach relevancy and acceptability of the charts to the elderly. RESULTS: 23% of the elderly had important limitations (values 4 and 5 of the charts) in physical fitness, 25% had unfavourable repercussions in feelings (values 4 and 5), 12% had important difficulties (value 4 and 5) in every-day life activities and 7% had important limitations in social life. 66% had no changes in their health in the last two weeks, 18% got better and 16% got worse. 21% valued their overall health as fair or poor, 47% as good and 24% as very good or excellent. Moderate to severe pain in the last two weeks was reported by 55% of the patients. Female reported in general worse scores than males. Statistical significance was found in the association between the number of the co-existent health problems in the same person (co-morbidity) and the values of some dimensions of the COOP/WONCA charts. In the half of the cases where the Katz index was measured there were non-concordance with the measures of the daily life of the COOP/WONCA charts. The charts had good acceptability and applicability but also some difficulties for illiterate elderly. DISCUSSION: Although the use of COOP/WONCA charts could be difficult with elderly patients the present study showed its applicability and utility in the everyday clinical practice. The charts open new possibilities for international comparisons on functional status assessment.

Activities of Daily Living↗

Descending projections from the caudal medulla oblongata to the superficial or deep dorsal horn of the rat spinal cord.

The location of neurons in the caudal medulla oblongata that project to the superficial or deep dorsal horn was studied in the rat, by means of retrograde labelling from confined spinal injection sites. The tracer cholera toxin subunit B was injected into laminae I-III (fuve rats) or I-V (three rats) at C4-7 spinal segments. Neurons projecting to the superficial dorsal horn were located in the dorsomedial part of the dorsal reticular nucleus ipsilaterally, the subnucleus commissuralis of the nucleus tractus solitarius bilaterally, and a region occupying the lateralmost part of the ventrolateral reticular formation between the lateral reticular nucleus and the caudal pole of the spinal trigeminal nucleus, pars caudalis, bilaterally. Neurons projecting to the deep dorsal horn, which were only labelled when laminae I-V were filled by the tracer, occurred in the dorsomedial and ventrolateral parts of the dorsal reticular nucleus and in the ventral reticular nucleus bilaterally. A few cells were located in the above described lateralmost portion of the ventrolateral reticular formation bilaterally and in the ventral portion of the ipsilateral cuneate nucleus. In the light of previous data demonstrating that dorsal horn neurons project to the dorsal reticular nucleus, the ventrolateral reticular formation, and the nucleus tractus solitarius, and that neurons in these three medullary regions are involved in pain inhibition at the spinal level, the descending projections demonstrated here suggest the occurrence of spino-medullary-spinal loops mediating the analgesic actions elicited in each nucleus upon the arrival of nociceptive input from the dorsal horn.

Animals↗

Carrageenan-induced inflammation of the hind foot provokes a rise of GABA-immunoreactive cells in the rat spinal cord that is prevented by peripheral neurectomy or neonatal capsaicin treatment.

An increase in the number of gamma-aminobutyric acid (GABA)-immunoreactive cells is reported in the superficial dorsal horn of the rat spinal cord upon unilateral inflammation of the hind foot caused by subcutaneous carrageenan injection. The rise of GABAergic cells was restricted to the ipsilateral dorsal horn, reaching a peak value of 23.4% over the contralateral side 4 days after carrageenan injection. Sciatic neurectomy or neonatal capsaicin treatment prevented this effect. These findings suggest that dorsal horn GABA is up-regulated by the increase of noxious inflow conveyed by unmyelinated C fibers from the inflamed tissues.

Animals↗

Neurons in the superficial dorsal horn of the rat spinal cord projecting to the medullary ventrolateral reticular formation express c-fos after noxious stimulation of the skin.

The nociceptive nature of the neurons of the superficial dorsal horn (laminae I-III) which project to the medullary ventrolateral reticular formation is studied in the rat. Medullary injections of Fluoro-Gold showed exclusive retrograde labeling of laminae I-III cells when the tracer filled a zone intermediate between the lateral tip of the lateral reticular nucleus and the spinal trigeminal nucleus, pars caudalis. This zone is here called VLMlat. Following noxious mechanical or thermal stimulation of the skin, double-labeled neurons, which stained retrogradely and were Fos-immunoreactive, prevailed in laminae I and IIo. Double-labeled neurons were few in lamina IIi after thermal stimulation and entirely lacking in lamina III after the two kinds of stimulation. Findings in lamina I confirm previous electrophysiological data (see Menétrey et al., J. Neurophysiol., 52 (1984) 595-611) showing that lamina I cells projecting to the ventrolateral reticular medulla convey noxious messages. The occurrence of numerous double-labeled cells in lamina IIo suggests that this lamina is also involved in nociceptive transmission to the VLMlat.

Animals↗

GABA decreases in the spinal cord dorsal horn after peripheral neurectomy.

A significant fall in the number of GABA-immunoreactive cells in laminae I-III of the rat spinal cord occurred in the somatotopic area of projection of the sciatic nerve after nerve transection. The decrease started at 2 weeks post-neurectomy, and at 4 weeks ipsilateral mean cell numbers were approximately 72% of contralateral control values. Similarly, the concentration of GABA in spinal homogenates was significantly reduced 4 weeks post-neurectomy. These data, together with our recent finding of an increase in spinal GABA during chronic inflammation of the hindlimb, suggest that the level of GABA in the dorsal horn is regulated by the amount of primary afferent input.

Animals↗