Iriana Galán-arriero - Academia.edu (original) (raw)

Papers by Iriana Galán-arriero

Tesis Doctoral leida en la Universidad Rey Juan Carlos de Madrid en 2016. Director de la Tesis: J... more Tesis Doctoral leida en la Universidad Rey Juan Carlos de Madrid en 2016. Director de la Tesis: Julian Taylor

Spinal Cord, 2016

Study design: Although abnormal cutaneous reflex (CR) activity has been identified during gait af... more Study design: Although abnormal cutaneous reflex (CR) activity has been identified during gait after incomplete spinal cord injury (SCI), this activity has not been directly compared in subjects with and without the spasticity syndrome. Objectives: Characterisation of CR activity during controlled rest and 'ramp and hold' phases of controlled plantarflexion in subjects with and without the SCI spasticity syndrome. Design: Transverse descriptive study with non-parametric group analysis. Setting: SCI rehabilitation hospital. Methods: Tibialis Anterior (TA) reflexes were evoked by innocuous cutaneous plantar sole stimulation during rest and ramp and hold phases of plantarflexion torque in non-injured subjects (n = 10) and after SCI with (n = 9) and without (n = 10) hypertonia and/or involuntary spasm activity. Integrated TA reflex responses were analysed as total (50-300 ms) or short (50-200 ms) and long-latency (200-300 ms) activity. Results: Total and long-latency TA activity was inhibited in non-injured subjects and the SCI group without the spasticity syndrome during plantarflexion torque but not in the SCI spasticity group. Furthermore, loss of TA reflex inhibition during plantarflexion correlated with time after SCI (ρ = 0.79, P = 0.009). Moreover, TA reflex activity inversely correlated with maximum plantarflexion torque in the spasticity group (ρ = − 0.75, P = 0.02), despite similar non-reflex TA electromyographic activity during plantarflexion after SCI in subjects with (0.11, 0.08-0.13 mV) or without the spasticity syndrome (0.09, 0.07-0.12 mV). Conclusions: This reflex testing procedure supports previously published evidence for abnormal CR activity after SCI and may characterise the progressive disinhibition of TA reflex activity during controlled plantarflexion in subjects diagnosed with the spasticity syndrome.

Introduction Spinal cord injury (SCI) often leads to sensorimotor dysfunction, including paralysi... more Introduction Spinal cord injury (SCI) often leads to sensorimotor dysfunction, including paralysis, spasticity and neuropathic pain, which directly impacts quality of life. Several pathophysiological mechanisms contribute to SCI, including neuroinflammation, oxidative stress, edema and neurodegeneration. Acute spinal contusion often involves an acute haemorrhage and expansion which represents a secondary pathological process of necrosis as a consequence of a progressive failure of blood capillary integrity (1). These secondary events also induce ischaemia and tissue hypoxia, while blood accumulation within the spinal cord causes further neuronal cell death due to haemotoxicity (2). Recently it has been postulated that haemorrhage within the spinal cord is associated with changes in sensorimotor function, includ-ing neuropathic pain and spasticity after SCI (3). In this preliminary study the clinical impact of spinal haemorrhage secondary to complete cervical SCI on sensorimotor func...

Pain, 2014

The p38a mitogenous activated protein kinase (MAPK) cell signaling pathway is a key mechanism of ... more The p38a mitogenous activated protein kinase (MAPK) cell signaling pathway is a key mechanism of microglia activation and has been studied as a target for neuropathic pain. The effect of UR13870, a p38a MAPK inhibitor, on microglia expression in the anterior cingulate cortex (ACC) and spinal dorsal horn was addressed after T9 contusion spinal cord injury (SCI) in the rat, in addition to behavioral testing of pain-related aversion and anxiety. Administration of intravenous UR13870 (1 mg/kg i.v.) and pregabalin (30 mg/kg i.v.) reduced place escape avoidance paradigm (PEAP) but did not affect open-field anxiety behavior 42 days after SCI. PEAP behavior was also reduced in animals administered daily with oral UR13870 (10 mg/kg p.o.) and preserved spinal tissue 28 days after SCI. Although UR13870 (10 mg/kg p.o.) failed to reduce OX-42 and glial fibrillar acid protein immunoreactivity within the spinal dorsal horn, a reduction toward the control level was observed close to the SCI site. In the anterior cingulate cortex (ACC), a significant increase in OX-42 immunoreactivity was identified after SCI. UR13870 (10 mg/kg p.o.) treatment significantly reduced OX-42, metabotropic glutamate type 5 receptor (mGluR5), and NMDA (N-methyl-d-aspartate) 2B subunit receptor (NR2B) expression in the ACC after SCI. To conclude, oral treatment with a p38a MAPK inhibitor reduces the affective behavioral component of pain after SCI in association with a reduction of microglia and specific glutamate receptors within the ACC. Nevertheless the role of neuroinflammatory processes within the vicinity of the SCI site in the development of affective neuropathic pain cannot be excluded.

Biosystems & Biorobotics, 2013

Spasticity is an important sensorimotor disorder that affects between 65-78% of people with spina... more Spasticity is an important sensorimotor disorder that affects between 65-78% of people with spinal cord injury (SCI). Although the standard diagnosis of spasticity relies on the standard measurement of hypertonia and stretch hyperreflexia, these symptoms are often described by patients as beneficial and may only play a limited role in motor dysfunction. In contrast related spasticity signs, such as involuntary muscle contractions (spasms) and cutaneous long-latency hyperreflexia, may be more problematic for residual motor function and general daily activities. As such there is a real need to characterize the impact of the symptoms of spasticity on neurological, functional, and daily activity during SCI rehabilitation. In this lecture the diagnostic utility of cutaneous hyperreflexia during both active and passive movement, as a possible hallmark of SCI spasticity will be discussed, in addition to its tractability to novel pharmacological and sensory neurorehabilitative strategies designed to modulate this specific sign of motor dysfunction.

European journal of pain (London, England), 2015

Recently, fatty acids have been shown to modulate sensory function in animal models of neuropathi... more Recently, fatty acids have been shown to modulate sensory function in animal models of neuropathic pain. In this study, the antinociceptive effect of 2-hydroxyoleic acid (2-OHOA) was assessed following spared nerve injury (SNI) with reflex and cerebrally mediated behavioural responses. Initial antinociceptive behavioural screening of daily administration of 2-OHOA (400 mg/kg, p.o.) was assessed in Wistar rats by measuring hindlimb reflex hypersensitivity to von Frey and thermal plate stimulation up to 7 days after SNI, while its modulatory effect on lumbar spinal dorsal horn microglia reactivity was assessed with OX-42 immunohistochemistry. In vitro the effect of 2-OHOA (120 μM) on cyclooxygenase protein expression (COX-2/COX-1 ratio) in lipopolysaccharide-activated macrophage cells was tested with Western blot analysis. Finally, the effects of 2-OHOA treatment on the place escape aversion paradigm (PEAP) and the open-field-induced anxiety test were tested at 21 days following nerve...

Neuroscience Letters, 2013

h i g h l i g h t s • Effects of cervical repetitive magnetic stimulation (rMS) on thermal thresh... more h i g h l i g h t s • Effects of cervical repetitive magnetic stimulation (rMS) on thermal thresholds. • 20 Hz cervical rMS increased warm threshold only within the local dermatome. • 1 Hz cervical rMS increased warm threshold within local and thoracic dermatomes. • No modulation of warm threshold within the V3 remote dermatome. • This technique holds promise for the neuromodulation of thermal pain.

Journal of the Neurological Sciences, 2013

Background: Central neuropathic pain (NP) is associated with change in endogenous pain modulation... more Background: Central neuropathic pain (NP) is associated with change in endogenous pain modulation (EPM) evoked by heterotopic noxious conditioning stimulation (HNCS). Objective: Characterise EPM disruption in patients with NP following spinal cord injury (SCI) and its relationship with contact heat evoked potentials (CHEPs). Methods: Ten healthy subjects and 20 patients with SCI (injury level below Th2) were recruited, 10 of which presented non-evoked NP (N5/10 NRS). Cz/Fz-CHEPs with corresponding perception of evoked heat pain (EvHP) from the C6 dermatome were assessed. Test stimulation (TS) was a 30 s tonic heat stimulus with the plateau intensity set individually at the temperature that evoked 3/10 (0-10, NRS, "pain-3"). The HNCS was a 30 s immersion of the contralateral hand in an innocuous (33°C) or painful (12°C) water bath. Subjects performed three protocols: non-conditioned TS; innocuous-HNCS TS and noxious-HNCS TS. TS pain intensity was assessed at 10 s (t1), 20 s (t2) and 30 s (t3). Results: Significant net t1 EPM of TS intensity was evoked in the healthy (−1.0 ± 0.3; p b 0.01) and SCI-noNP groups (−0.8 ± 0.3; p b 0.05), but not in the SCI-NP group (+ 0.2 ± 0.3; p N 0.05). Mean net t1-t3 EPM was different between the healthy and SCI-NP groups (p = 0.04). Importantly mean net t1-t3 EPM correlated highly with the CHEP amplitude only in patients with SCI-NP (rho = 0.8; p = 0.015), suggesting that disruption of EPM following NP may be quantified with this objective biomarker of pain perception. Conclusion: Endogenous inhibitory pain modulation is lost in subjects with SCI NP and is reflected by an increase in sensory evoked potentials in response to contact heat stimulation.

Biosystems & Biorobotics, 2014

ABSTRACT Tibialis Anterior (TA) electromyographic coherence estimation is assumed to reflect comm... more ABSTRACT Tibialis Anterior (TA) electromyographic coherence estimation is assumed to reflect common supraspinal descending input spinal motoneurons, related to corticospinal tract activity. This study documented residual voluntary motor recovery at 2 week intervals during subacute spinal cord injury (SCI) with intramuscular TA EMG coherence estimation within the 10-60Hz bandwidth, assessed during controlled maximal isometric and isokinetic dorsiflexion. Several clinical and functional lower limb measures (muscular testing, dorsiflexion maximal voluntary torque and gait function measured with the WISCI II) and neurophysiological measures (TA motor evoked potentials, MEPs) were also recorded. Total and TA muscle strength, voluntary torque generation and gait function improved during subacute SCI, in addition to 40-60Hz, but not 15-30Hz intramuscular TA coherence. TA MEPs failed to reflect significant recovery of function. The SCI spasticity syndrome non-specifically reduced 15-30Hz TA coherence and was detected as high TA coherence values during fast isokinetic movement in all frequency bands. To conclude, longitudinal assessment of adaptive and maladaptive motor plasticity during subacute SCI can be detected with TA EMG coherence estimation during controlled movement, providing orientative diagnostic information during neurorehabilitation.

Sensorimotor dysfunction following incomplete spinal cord injury (iSCI) is often characterized by... more Sensorimotor dysfunction following incomplete spinal cord injury (iSCI) is often characterized by the debilitating symptoms of paralysis, spasticity and pain, which require treatment with novel pleiotropic pharmacological agents. Previous in vitro studies suggest that Albumin (Alb) and Oleic Acid (OA) may play a role together as an endogenous neurotrophic factor. Although Alb can promote basic recovery of motor function after iSCI, the therapeutic effect of OA or Alb-OA on a known translational measure of SCI associated with symptoms of spasticity and change in nociception has not been studied. Following T9 spinal contusion injury in Wistar rats, intrathecal treatment with: i) Saline, ii) Alb (0.4 nanomoles), iii) OA (80 nanomoles), iv) Alb-Elaidic acid (0.4/80 nanomoles), or v) Alb-OA (0.4/80 nanomoles) were evaluated on basic motor function, temporal summation of noxious reflex activity, and with a new test of descending modulation of spinal activity below the SCI up to one month ...

Neuroscience Letters

Microglia cell activation plays a role in the development of neuropathic pain partly due to the a... more Microglia cell activation plays a role in the development of neuropathic pain partly due to the activation of the p38α MAPK signaling pathway after nerve injury. In this study we assessed the effect of UR13870, a p38α MAPK inhibitor, in the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;spared nerve injury&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; (SNI) model, to study its effects on modulation of spinal microglial activation and to test behavioral hyperreflexia responses and cerebral-mediated pain behavior. The effect of daily administration of UR13870 (10mg/kg p.o.) and Pregabalin (50mg/kg p.o.) on reflex hypersensitivity to mechanical and cold test stimuli and on affective related pain responses measured with the place escape avoidance paradigm and the open field-induced anxiety test, were evaluated after SNI in Sprague Dawley rats. Microglial reactivity in the ipsilateral lumbar laminae I/II dorsal horn was evaluated with OX-42 immunohistochemistry. UR13870 treatment significantly decreased hindlimb hyperreflexia to both mechanical and cold stimuli after SNI without loss of general motor function, in addition to a reduction in pain-related anxiety behavior at day 21 after SNI, accompanied by normalization of OX-42 immunoreactivity within the ipsilateral lumbar dorsal horn. Pregabalin treatment only reduced mechanical hyperreflexia and affected general motor function. Oral administration of the p38α MAPK inhibitor, UR13870, mediates antinociception to both mechanical and cold stimuli, and significantly restored inner-zone exploration in the open field test, accompanied by normalization in dorsal horn microglial activation in the SNI model.

Journal of Manipulative and Physiological Therapeutics

The Clinical Journal of Pain

Journal of Electromyography and Kinesiology

PloS one, 2017

Sensorimotor dysfunction following incomplete spinal cord injury (SCI) is often characterized by ... more Sensorimotor dysfunction following incomplete spinal cord injury (SCI) is often characterized by paralysis, spasticity and pain. Previously, we showed that intrathecal (i.t.) administration of the albumin-oleic acid (A-OA) complex in rats with SCI produced partial improvement of these symptoms and that oral 2-hydroxyoleic acid (HOA, a non-hydrolyzable OA analogue), was efficacious in the modulation and treatment of nociception and pain-related anxiety, respectively. Here we observed that intrathecal treatment with the complex albumin-HOA (A-HOA) every 3 days following T9 spinal contusion injury improved locomotor function assessed with the Rotarod and inhibited TA noxious reflex activity in Wistar rats. To investigate the mechanism of action of A-HOA, microarray analysis was carried out in the spinal cord lesion area. Representative genes involved in pain and neuroregeneration were selected to validate the changes observed in the microarray analysis by quantitative real-time RT-PCR....

Medical & biological engineering & computing, Jan 17, 2018

Several studies have examined spinal reflex modulation during leg cycling in healthy and spinal c... more Several studies have examined spinal reflex modulation during leg cycling in healthy and spinal cord injury (SCI) subjects. However, the effect of cutaneous plantar afferent input on spinal excitability during leg cycling after SCI has not been characterised. The aim of the study was to test the feasibility of using controlled leg cycling in combination with plantar cutaneous electrical stimulation (ES) cycling to assess lower limb spinal sensorimotor excitability in subjects with motor complete or incomplete SCI. Spinal sensorimotor excitability was estimated by measuring cutaneomuscular-conditioned soleus H-reflex activity. Reflex excitability was tested before and after a 10-min ES cycling session in 13 non-injured subjects, 6 subjects with motor incomplete SCI (iSCI) who had moderately impaired gait function, 4 subjects with motor iSCI who had severely impaired gait function, and 5 subjects with motor complete SCI (cSCI). No modulation of soleus H-reflex with plantar cutaneous s...

Biochimica et biophysica acta, Sep 1, 2017

Omega-3 polyunsaturated fatty acids (PUFAs), such as docosaexaenoic acid (DHA) and eicosapentaeno... more Omega-3 polyunsaturated fatty acids (PUFAs), such as docosaexaenoic acid (DHA) and eicosapentaenoic acid (EPA), mediate neuroactive effects in experimental models of traumatic peripheral nerve and spinal cord injury. Cellular mechanisms of PUFAs include reduced neuroinflammation and oxidative stress, enhanced neurotrophic support, and activation of cell survival pathways. Bioactive Omega-9 monounsaturated fatty acids, such as oleic acid (OA) and 2-hydroxy oleic acid (2-OHOA), also show therapeutic effects in neurotrauma models. These FAs reduces noxious hyperreflexia and pain-related anxiety behavior following peripheral nerve injury and improves sensorimotor function following spinal cord injury (SCI), including facilitation of descending inhibitory antinociception. The relative safe profile of neuroactive fatty acids (FAs) holds promise for the future clinical development of these molecules as analgesic agents. This article is part of a Special Issue entitled: Membrane Lipid Thera...

Revista Latinoamericana de Cirugía Ortopédica, 2017