Back Mechanical Sensitivity Assessment in the Rat for Mechanistic Investigation of Chronic Back Pain.

Low back pain is the leading cause of disability worldwide, with dramatic personal, economic, and social consequences. To develop novel therapeutics, animal models are needed to examine the mechanisms and effectiveness of novel therapies from a translational perspective. Several rodent models of back pain are used in current investigations.

Spinal neurovascular coupling is preserved despite time-dependent alterations of spinal cord blood flow responses in a rat model of chronic back pain: implications for functional spinal cord imaging.

Functional magnetic resonance imaging has been used to investigate nociceptive processes in patients with chronic pain. However, the results may be confounded with changes in neurovascular coupling induced by chronic pain. The objective of this study was to examine spinal neurovascular coupling in a rat model of chronic back pain induced by muscle inflammation.

Attenuation of widespread hypersensitivity to noxious mechanical stimuli by inhibition of GABAergic neurons of the right amygdala in a rat model of chronic back pain.

Background: Chronic primary low back pain may be associated with hyperalgesia in uninjured tissues and with decreased pain inhibition. Previous studies have shown that the amygdala is involved in pain regulation and chronic pain, that neuronal activity in the amygdala is altered in models of persistent pain, and that the central nucleus of the right amygdala plays an active role in widespread hypersensitivity to noxious stimuli.

Methods: Behavioral, electrophysiological, biochemical, and chemogenetic methods were used to examine the role of the central nucleus of the right amygdala in hypersensitivity to noxious stimuli in a rat model of chronic back pain induced by a local injection of Complete Freund Adjuvant (CFA) in paraspinal muscles.

Fasting prevents medetomidine-induced hyperglycaemia and alterations of neurovascular coupling in the somatosensory cortex of the rat during noxious stimulation.

Medetomidine and isoflurane are commonly used for general anaesthesia in fMRI studies, but they alter cerebral blood flow (CBF) regulation and neurovascular coupling (NVC). In addition, medetomidine induces hypoinsulinemia and hyperglycaemia, which also alter CBF regulation and NVC. Furthermore, sudden changes in arterial pressure induced by noxious stimulation may affect NVC differently under medetomidine and isoflurane anaesthesia, considering their different effects on vascular functions.

Contribution of astrocytes to neurovascular coupling in the spinal cord of the rat.

Functional magnetic resonance imaging (fMRI) of the spinal cord relies on the integrity of neurovascular coupling (NVC) to infer neuronal activity from hemodynamic changes. Astrocytes are a key component of cerebral NVC, but their role in spinal NVC is unclear. The objective of this study was to examine whether inhibition of astrocyte metabolism by fluorocitrate alters spinal NVC.

Locomotor deficits induced by lumbar muscle inflammation involve spinal microglia and are independent of KCC2 expression in a mouse model of complete spinal transection.

Spinal cord injury (SCI) is associated with damage to musculoskeletal tissues of the spine. Recent findings show that pain and inflammatory processes caused by musculoskeletal injury mediate plastic changes in the spinal cord. These changes could impede the adaptive plastic changes responsible for functional recovery.

Biphasic Effect of Buspirone on the H-Reflex in Acute Spinal Decerebrated Mice.

Pharmacological treatment facilitating locomotor expression will also have some effects on reflex expression through the modulation of spinal circuitry. Buspirone, a partial serotonin receptor agonist (5-HT ), was recently shown to facilitate and even trigger locomotor movements in mice after complete spinal lesion (Tx). Here, we studied its effect on the H-reflex after acute Tx in adult mice.

Integration of bilateral nociceptive inputs tunes spinal and cerebral responses.

Together with the nociceptive system, pain protects the body from tissue damage. For instance, when the RIII-reflex is evoked by sural nerve stimulation, nociceptive inputs activate flexor muscles and inhibit extensor muscles of the affected lower limb while producing the opposite effects on the contralateral muscles. But how do the spinal cord and brain integrate concurrent sensorimotor information originating from both limbs? This is critical for evoking coordinated responses to nociceptive stimuli, but has been overlooked.

Regulation of cortical blood flow responses by the nucleus basalis of Meynert during nociceptive processing.

Cerebral blood flow (CBF) is essential for neuronal metabolic functions. CBF is partly regulated by cholinergic projections from the nucleus basalis of Meynert (NBM) during cortical processing of sensory information. During pain-related processing, however, this mechanism may be altered by large fluctuations in systemic mean arterial pressure (MAP).

Axons morphometry in the human spinal cord.

Due to the technical challenges of large-scale microscopy and analysis, to date only limited knowledge has been made available about axon morphometry (diameter, shape, myelin thickness, volume fraction), thereby limiting our understanding of neuronal microstructure and slowing down research on neurodegenerative pathologies. This study addresses this knowledge gap by establishing a state-of-the-art acquisition and analysis framework for mapping axon morphometry, and providing the first comprehensive mapping of axon morphometry in the human spinal cord. We dissected, fixed and stained a human spinal cord with osmium tetroxide, and used a scanning electron microscope to image the entirety of 23 axial slices, covering C1 to L5 spinal levels.

H-reflex disinhibition by lumbar muscle inflammation in a mouse model of spinal cord injury.

Inflammation is a common comorbidity in patients with traumatic spinal cord injury (SCI). Recent reports indicate that inflammation hinders functional recovery in animal models of SCI. However, the spinal mechanisms underlying this alteration are currently unknown.

Functional Neuroimaging of Nociceptive and Pain-Related Activity in the Spinal Cord and Brain: Insights From Neurovascular Coupling Studies.

Spinal cord and brain processes underlie pain perception, which produces systemic cardiovascular changes. In turn, the autonomic nervous system regulates vascular function in the spinal cord and brain in order to adapt to these systemic changes, while neuronal activity induces local vascular changes. Thus, autonomic regulation and pain processes in the brain and spinal cord are tightly linked and interrelated.

Facilitation of Locomotor Spinal Networks Activity by Buspirone after a Complete Spinal Cord Lesion in Mice.

Despite efforts to potentiate spinal cord lesioned (SCL) patients' functional recovery with multi-targeted therapy combining pharmacological treatment and training, consistent improvements in locomotor control by descending transmission or spinal network facilitation are still eluding clinicians and researchers. Lately, United States Food and Drug Administration-approved buspirone has shown promise and promoted locomotor-like movement occurrence in SCL patients, but evidence on how and where it exerts its effects is lacking. The objective of the present study was, first, to verify buspirone effect on locomotor spinal network and to evaluate if it promoted functional recovery when combined with training.

Isoflurane anesthesia does not affect spinal cord neurovascular coupling: evidence from decerebrated rats.

Neurological examination remains the primary clinical investigation in patients with spinal cord injury. However, neuroimaging methods such as functional magnetic resonance imaging (fMRI) are promising tools for following functional changes in the course of injury, disease and rehabilitation. However, the relationship between neuronal activity and blood flow in the spinal cord on which fMRI relies has been largely overlooked.

Lumbar muscle inflammation alters spinally mediated locomotor recovery induced by training in a mouse model of complete spinal cord injury.

Locomotor networks after spinal cord injury (SCI) are shaped by training-activated proprioceptive and cutaneous inputs. Nociception from injured tissues may alter these changes but has largely been overlooked. The objective of the present study was to ascertain whether lumbar muscle inflammation hinders locomotion recovery in a mouse model of complete SCI.

Tight neurovascular coupling in the spinal cord during nociceptive stimulation in intact and spinal rats.

Functional magnetic resonance imaging (fMRI) is based on neurovascular coupling, which allows inferring neuronal activity from hemodynamic changes. Spinal fMRI has been used to examine pain processes, although spinal neurovascular coupling has never been investigated. In addition, fluctuations in mean arterial pressure (MAP) occur during nociceptive stimulation and this may affect neurovascular coupling.

A pneumatic phantom for mimicking respiration-induced artifacts in spinal MRI.

Purpose: To design a phantom capable of mimicking human respiration to serve as a testing platform for correction of the static and time-evolving magnetic field distortions typically encountered in MRI of the spinal cord.

Methods: An inflation system to mimic the air variation of the human lungs was constructed. The inflation system was linked to a phantom containing synthetic lungs and an ex vivo human spine.

Systemic blood pressure alters cortical blood flow and neurovascular coupling during nociceptive processing in the primary somatosensory cortex of the rat.

Inference on nociceptive and pain-related processes from functional magnetic resonance imaging is made with the assumption that the coupling of neuronal activity and cerebral hemodynamic changes is stable. However, since nociceptive stimulation is associated with increases in systemic arterial pressure, it is essential to determine whether this coupling remains the same during different levels of nociception and pain. The main objective of the present study was to compare the amplitude of local field potentials (LFP) and cerebral blood flow (CBF) changes in the primary somatosensory cortex during nociceptive electrical stimulation of the contralateral or ipsilateral forepaw in isoflurane-anesthetized rats, while manipulating mean arterial pressure (MAP).

Coxofemoral joint kinematics using video fluoroscopic images of treadmill-walking cats: development of a technique to assess osteoarthritis-associated disability.

The objectives of this pilot study were to develop a video fluoroscopy kinematics method for the assessment of the coxofemoral joint in cats with and without osteoarthritis (OA)-associated disability. Two non-OA cats and four cats affected by coxofemoral OA were evaluated by video fluoroscopy. Video fluoroscopic images of the coxofemoral joints were captured at 120 frames/s using a customized C-arm X-ray system while cats walked freely on a treadmill at 0.

Split-belt walking alters the relationship between locomotor phases and cycle duration across speeds in intact and chronic spinalized adult cats.

During overground or treadmill walking, the stance phase and cycle durations are reduced as speed increases, whereas swing phase duration remains relatively invariant. When the speed of the left and right sides is unequal, as is the case during split-belt locomotion or when walking along a circular path, adjustments in stance and swing phases are observed, which could alter the phase/cycle duration relationships. Here, we tested this hypothesis in the left and right hindlimbs of four intact and two chronic spinal-transected adult cats during tied-belt (i.

Effect of locomotor training in completely spinalized cats previously submitted to a spinal hemisection.

After a spinal hemisection in cats, locomotor plasticity occurring at the spinal level can be revealed by performing, several weeks later, a complete spinalization below the first hemisection. Using this paradigm, we recently demonstrated that the hemisection induces durable changes in the symmetry of locomotor kinematics that persist after spinalization. Can this asymmetry be changed again in the spinal state by interventions such as treadmill locomotor training started within a few days after the spinalization? We performed, in 9 adult cats, a spinal hemisection at thoracic level 10 and then a complete spinalization at T13, 3 weeks later.

Incomplete spinal cord injury promotes durable functional changes within the spinal locomotor circuitry.

While walking in a straight path, changes in speed result mainly from adjustments in the duration of the stance phase while the swing phase remains relatively invariant, a basic feature of the spinal central pattern generator (CPG). To produce a broad range of locomotor behaviors, the CPG has to integrate modulatory inputs from the brain and the periphery and alter these swing/stance characteristics. In the present work we raise the issue as to whether the CPG can adapt or reorganize in response to a chronic change of supraspinal inputs, as is the case after spinal cord injury (SCI).

Recovery of hindlimb locomotion after incomplete spinal cord injury in the cat involves spontaneous compensatory changes within the spinal locomotor circuitry.

After incomplete spinal cord injury (SCI), compensatory changes occur throughout the whole neuraxis, including the spinal cord below the lesion, as suggested by previous experiments using a dual SCI paradigm. Indeed, cats submitted to a lateral spinal hemisection at T10-T11 and trained on a treadmill for 3-14 wk re-expressed bilateral hindlimb locomotion as soon as 24 h after spinalization, a process that normally takes 2-3 wk when a complete spinalization is performed without a prior hemisection. In this study, we wanted to ascertain whether similar effects could occur spontaneously without training between the two SCIs and within a short period of 3 wk in 11 cats.

Kinematic study of locomotor recovery after spinal cord clip compression injury in rats.

After spinal cord injury (SCI), precise assessment of motor recovery is essential to evaluate the outcome of new therapeutic approaches. Very little is known on the recovery of kinematic parameters after clinically-relevant severe compressive/contusive incomplete spinal cord lesions in experimental animal models. In the present study we evaluated the time-course of kinematic parameters during a 6-week period in rats walking on a treadmill after a severe thoracic clip compression SCI.

Chapter 2--the spinal generation of phases and cycle duration.

During walking, an increase in speed is accompanied by a decrease in the stance phase duration while the swing phase remains relatively invariant. By definition, the rhythm generator in the lumbar spinal cord controls cycle period, phase durations, and phase transitions. Our first aim was to determine if this asymmetry in the control of locomotor cycles is an inherent property of the central pattern generator (CPG).