Eduardo Malmierca

Corticofugal action on somatosensory response properties of rat nucleus gracilis cells

Single unit recordings were performed in the nucleus gracilis (Gr) of anesthetized rats to study the influences of the sensorimotor corticofugal projections on sensory responses of those cells. The effects of electrical stimulation of contralateral primary sensory cortex were studied in two conditions: when the receptive fields of the stimulated cortical area and the gracilis cells overlapped (matched) or when they were completely different (unmatched). Cortical stimulation at low intensities (<50 microA) evoked spike firing only in gracilis neurons with matched receptive fields. When the receptive fields were unmatched, the intensity of the stimulation had to be increased above 50 microA to elicit spike firing. To study the corticofugal actions on the responses of Gr neurons, the onset of peripheral stimulation was likened to a single cortical shock in the sensorimotor cortex. When receptive fields matched, cortical stimulation facilitated the cellular responses to the natural sensory stimulation of their RF in most of the Gr neurons (86%). In the unmatched receptive fields, cortical stimulation could either inhibit (66.7%), facilitate (20.8%) or did not modify (12.5%) the sensory response at all. Trains of cortical shocks during sensory stimulation demonstrated that the facilitatory and inhibitory effects on Gr neurons outlasted the period of stimulation by 30-60 s. Results indicate that the sensorimotor cortex exercises a very precise control of sensory transmission throughout the Gr nucleus and suggest that the corticofugal projection may play an important role in the plasticity of the sensorimotor system.

Neuronal disinhibition in the trigeminal nucleus caudalis in a model of chronic neuropathic pain.

The mechanisms underlying neuropathic facial pain syndromes are incompletely understood. We used a unilateral chronic constriction injury of the rat infraorbital nerve (CCI‐IoN) as a facial neuropathic model. Pain‐related behavior of the CCI‐IoN animals was tested at 8, 15 and 26 days after surgery (dps). The response threshold to mechanical stimulation with von Frey hairs on the injured side was reduced at 15 and 26 dps, indicating the presence of allodynia. We performed unitary recordings in the caudalis division of the spinal trigeminal nucleus (Sp5C) at 8 or 26 dps, and examined spontaneous activity and responses to mechanical and thermal stimulation of the vibrissal pad. Neurons were identified as wide dynamic range (WDR) or low‐threshold mechanoreceptive (LTM) according to their response to tactile and/or noxious stimulation. Following CCI‐IoN, WDR neurons, but not LTM neurons, increased their spontaneous activity at 8 and 26 dps, and both types of Sp5C neurons increased their responses to tactile stimuli. In addition, the on–off tactile response in neurons recorded after CCI‐IoN was followed by afterdischarges that were not observed in control cases. Compared with controls, the response inhibition observed during paired‐pulse stimulation was reduced after CCI‐IoN. Immunohistochemical studies showed an overall decrease in GAD65 immunoreactivity in Sp5C at 26 dps, most marked in laminae I and II, suggesting that following CCI‐IoN the inhibitory circuits in the sensory trigeminal nuclei are depressed. Consequently, our results strongly suggest that disinhibition of Sp5C neurons plays a relevant role in the appearance of allodynia after CCI‐IoN.

Primary somatosensory cortex modulation of tactile responses in nucleus gracilis cells of rats

Corticofugal influences from the primary somatosensory cortex to the gracilis nuclei were studied with single unit recordings performed in urethane‐anaesthetized rats. Two types of neurons were identified: low firing rate (LF) neurons, which could be activated antidromically by medial lemniscus stimulation; and high firing rate (HF) neurons. The effects of electrically stimulating the contralateral primary somatosensory cortex were studied in two situations: when the stimulated cortical area and specific gracilis cells had overlapping receptive fields and when the receptive fields of the cells and primary somatosensory cortex did not overlap. Cortical stimulation facilitated cortical and tactile responses in most gracilis neurons (68% and 58% for LF and HF neurons, respectively) with overlapping receptive fields. When receptive fields were different, cortical stimulation inhibited tactile response in most LF neurons (58%) and some HF neurons (20%). Trains of cortical shocks during sensory stimulation demonstrated that the facilitatory and inhibitory effects outlasted the stimulation period by 5 min. The facilitatory effect was decreased by iontophoretic application of the N‐methyl‐D‐aspartate (NMDA) receptor antagonist APV (50 mm). However, APV did not modify the intensity of the tactile response inhibition in cells with nonoverlapping receptive fields, although, its duration was decreased (<5 min). Iontophoretic application of the γ‐aminobutyric acid (GABA)A antagonist bicuculline (20 mm) blocked the cortically evoked inhibition in cells with nonoverlapping receptive fields. The results indicate that the somatosensory cortex precisely controls somatosensory transmission throughout the gracilis nucleus by means of NMDA and GABAA receptor activation.

Characteristics of louse-borne relapsing fever in Ethiopian children and adults

Abstract Louse-borne relapsing fever (LBRF) is endemic in Ethiopia. The epidemiological and clinical aspects of LBRF and the differences between the infection in children and that in adults were investigated in a rural hospital in Ethiopia. During the 5-year study (1997-2002), 197 patients had a confirmed diagnosis of LBRF. Most (62.1%) of the cases were children under 15 years of age. The adult cases (i.e. those aged ≥15 years) were far more likely to present with headache (76.9% v. 40%; P <0.001), musculo-skeletal pains (61.5% v. 30.5%; P <0.001), dizziness (64% v. 39%; P =0.002) and bleeding (16.9% v. 3.8%; P =0.005) than the paediatric. The overall level of case fatality was 6.4%. Death appeared to be significantly associated with adulthood (P =0.01), delay in consultation (P =0.026) and the presence of vomiting (P =0.023). LBRF is clearly still a public-health problem in Ethiopia, where the clinical manifestations of the disease differ according to the age of the case.

Results of a 10-year survey of louse-borne relapsing fever in southern Ethiopia: a decline in endemicity

When transmitted from person to person by the human body louse, Pediculus humanus humanus, the spirochaete Borrelia recurrentis can cause an acute febrile illness. In the highlands of Ethiopia, this illness, which is known as louse-borne relapsing fever (LBRF), has probably been endemic for centuries and, until the last few years, epidemics of the disease have been common (Borgnolo et al., 1993). The outbreaks that occurred in northern Ethiopia in the 1990s were attributed to the return of soldiers to their original recruitment areas, after the end of 30 years of fighting against Eritrea (Borgnolo et al., 1993; Sundnes and Haimanot, 1993). In the catchment area for the Gambo General Rural Hospital (GGRH), which lies, at about 2200 m above sea level, on the eastern escarpment of the Great Rift Valley, about 250 km to the south of Addis Ababa, LBRF has been endemic for many years. Ramos et al. (2004) described the 197 cases identified in this area between 1997 and 2002. Encouragingly, however, no new cases of the disease have been detected in this area since early in 2005, raising the possibility that the disease in no longer locally endemic. The trends in LBRF seen in this region in the last decade are described and discussed below. During the study period (11 September 1997–10 September 2007), 579,136 patients attended the outpatients’ department of the GGRH, of whom 251 were found to have Borrelia infection (by microscopical examination of their bloodsmears) and were therefore recorded as cases of LBRF. Although this gives an overall incidence, over the study decade, of 4.3 cases/10,000 outpatients, this value does not show the remarkable fall seen in annual incidence. Over half (58%) of all the cases detected in the decade occurred in the first 3 years but only four (1.6%) occurred in the last 3 years (see Table). The highest monthly numbers of LBRF cases were seen in February–November 1998 (see Figure). In each of the months between this peak and February 2005 (except for six scattered months when no cases were seen), between one and eight cases of the disease presented at the GGRH. Since March 2005, however, no new cases have been diagnosed. The seasonality of LBRF in Ethiopia is unclear. While Parry et al. (1970) observed a peak in incidence during the ‘big rains’ (known locally as kiremt), which fall between June and September, Daniel et al. (1992) subsequently found incidence to peak during the ‘small rains’ (belg), which fall between March and May. No marked seasonality was observed in the present study, with 53 (21.1%) of the cases diagnosed during the big rains and 80 (31.9%) during the small rains. In Ethiopia, LBRF has been both an epidemic problem, with outbreaks associated with war, military personnel and refugee camps (Borgnolo et al., 1993; Sundnes and Haimanot, 1993), and an endemic problem, with a relatively small but steady stream of cases presenting for treatment (Mitiku and Mengistu, 2002). Until 2005 — assuming that the 1998 peak in the numbers of cases presenting can be considered an outbreak — this was the picture at the GGRH. Since mid-2005, however, no cases of LBRF have been recorded at the GGRH, possibly indicating Annals of Tropical Medicine & Parasitology, Vol. 102, No. 5, 467–469 (2008)

Inhibitory control of nociceptive responses of trigeminal spinal nucleus cells by somatosensory corticofugal projection in rat

The caudal division of the trigeminal spinal nucleus (Sp5C) is an important brainstem relay station of orofacial pain transmission. The aim of the present study was to examine the effect of cortical electrical stimulation on nociceptive responses in Sp5C neurons. Extracellular recordings were performed in the Sp5C nucleus by tungsten microelectrodes in urethane-anesthetized Sprague-Dawley rats. Nociceptive stimulation was produced by application of capsaicin cream on the whisker pad or by constriction of the infraorbital nerve. Capsaicin application evoked a long-lasting increase in the spontaneous firing rate from 1.4±0.2 to 3.4±0.6 spikes/s. Non-noxious tactile responses from stimuli delivered to the receptive field (RF) center decreased 5 min. after capsaicin application (from 2.3±0.1 to 1.6±0.1 spikes/stimulus) while responses from the whisker located at the RF periphery increased (from 1.3±0.2 to 2.0±0.1 spikes/stimulus under capsaicin). Electrical train stimulation of the primary (S1) or secondary (S2) somatosensory cortical areas reduced the increase in the firing rate evoked by capsaicin. Also, S1, but not S2, cortical stimulation reduced the increase in non-noxious tactile responses from the RF periphery. Inhibitory cortical effects were mediated by the activation of GABAergic and glycinergic neurons because they were blocked by bicuculline or strychnine. The S1 and S2 cortical stimulation also inhibited Sp5C neurons in animals with constriction of the infraorbital nerve. Consequently, the corticofugal projection from S1 and S2 cortical areas modulates nociceptive responses of Sp5C neurons and may control the transmission of nociceptive sensory stimulus.

Louse-borne relapsing fever in Ethiopian children: experience of a rural hospital.

We describe the epidemiological and clinical aspects of louse-borne relapsing fever (LBRF) in a series of children attending in a rural hospital in Ethiopia during 1997–2007. From a total of 249 cases of LBRF, 154 (61.4%) were children (> 15 years). The most frequent symptoms were: fever, headache, dizziness and musculoskeletal pains. The overall case fatality rate was 2.4 (10% for patients < 1.1 years; 3.4% for 1.1 to 4.0 years; and 0% >4.0 years [P = 0.05]). The mortality in children was less than in adults (13.2%) (P = 0.003).

Corticofugal projections induce long-lasting effects on somatosensory responses in the trigeminal complex of the rat

The sensory information flow at subcortical relay stations is controlled by the action of topographic connections from the neocortex. To determinate the functional properties of the somatosensory corticofugal projections to the principal (Pr5) and caudal spinal (Sp5C) trigeminal nuclei, we performed unitary recordings in anesthetized rats. To examine the effect of these cortical projections we used tactile stimulation of the whisker and electrical stimulation of somatosensory cortices. Corticofugal anatomical projections to Pr5 and Sp5C nuclei were detected by using retrograde fluorescent tracers. Neurons projecting exclusively to Pr5 were located in the cingulate cortex while neurons projecting to both Sp5C and Pr5 nuclei were located in the somatosensory and insular cortices (>75% of neurons). Physiological results indicated that primary somatosensory cortex produced a short-lasting facilitating or inhibiting effects (<5 min) of tactile responses in Pr5 nucleus through activation of NMDA glutamatergic or GABAA receptors since effects were blocked by iontophoretically application of APV and bicuculline, respectively. In contrast, stimulation of secondary somatosensory cortex did not affect most of the Pr5 neurons; however both cortices inhibited the nociceptive responses in the Sp5C nucleus through activation of glycinergic or GABAA receptors because effects were blocked by iontophoretically application of strychnine and bicuculline, respectively. These and anatomical results demonstrated that the somatosensory cortices projects to Pr5 nucleus to modulate tactile responses by excitatory and inhibitory actions, while projections to the Sp5C nucleus control nociceptive sensory transmission by only inhibitory effects. Thus, somatosensory cortices may modulate innocuous and noxious inputs simultaneously, contributing to the perception of specifically tactile or painful sensations.

Louse-borne relapsing fever and malaria co-infection in Ethiopia

observation could be due to the high cost of insulin drugs and a lack of adequate home monitoring culture among the patients. These, coupled with poverty – which makes it almost impossible for patients to go in for regular lipid profile testing and maintain regular drug regimen together with poor diet and physical activity management – could be blamed for the high prevalence rates. These factors are worth noting, especially among the IDDM patients as their cases are insulin-dependent, and as they are mainly youths, they may not have the financial muscle and thus are dependent on a guardian to attend regular check-ups. This result suggests that atherosclerosis may be accelerated in these patients and that they may be more prone to the development of coronary heart disease. We call for government subsidization of the cost of treatment and testing regimen of hyperlipidaemiaassociated DM to ensure adequate monitoring, treatment and reduction of dyslipidaemia among diabetics, especially in Africa.

Neuron synchronization in the rat gracilis nucleus facilitates sensory transmission in the somatosensory pathway

We have studied the role of the temporal correlation of multiple cell discharges in the facilitation of the somatosensory information transmission from the gracilis nucleus to the primary somatosensory (SI) cortex in anesthetized rats. Pairs of gracilis neurons or gracilis–SI cortical neurons were recorded during application of 20‐ms tactile stimuli in control conditions and after electrical corticofugal stimulation. Cross‐correlation of neural spike trains showed significant changes in synchronization of the neuron firing provoked by the corticofugal stimulation. To quantify the time–frequency alterations in the functional association within neuron pairs we used the wavelet coherence measure. We show that electrical stimulation of the SI cortex induces a short‐lasting facilitation of tactile responses of projecting gracilis neurons if their receptive fields (RFs) overlap with the RF of the stimulated cortical area (matching condition). Moreover, synchronization of discharges of gracilis neurons with a common RF is increased by activation of the corticofugal projection. Synchronization is favored by a stimulus induced synchronous oscillatory activity of projecting neurons in the range 3–10 Hz. In the matching condition synchronous discharges in the gracilis increment the number of spikes elicited in the SI cortex. Thus the efficacy of the sensory transmission from the gracilis nucleus to the SI cortex is modulated by the corticofugal projection through two complementary mechanisms: (i) by changing the responsiveness (number of elicited spikes) of individual gracilis neurons; and (ii) by a dynamic consolidation of gracilis neurons with a common RF into microcircuits generating synchronous spikes.