Neuroplasticity of ascending and descending pathways after somatosensory system injury: reviewing knowledge to identify neuropathic pain therapeutic targets

Boadas-Vaello, Pere; Castany, Sílvia; Homs, Judit; Álvarez-Pérez, Beltrán; Deulofeu, Meritxell; Verdú, Enrique

doi:10.1038/sc.2015.225

Cited by 83 publications

(69 citation statements)

References 144 publications

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“…Chronic CNS pathologies, including epilepsy, Alzheimer’s and Parkinson’s diseases, multiple sclerosis, amyotrophic lateral sclerosis and neuropathic pain [1-6] as well as acute brain injuries with long term neurological sequelae such as infections, stroke and neurotrauma [7, 8] display similar neuronal network reorganizations, suggesting the presence of shared pathogenic mechanisms. A common hallmark of these conditions is the presence of neuroinflammation [9-12].…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammation Alters Integrative Properties of Rat Hippocampal Pyramidal Cells

et al. 2018

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Neuroinflammation is consistently found in many neurological disorders, but whether or not the inflammatory response independently affects neuronal network properties is poorly understood. Here, we report that intracerebroventricular injection of the prototypical inflammatory molecule lipopolysaccharide (LPS) in rats triggered a strong and long lasting inflammatory response in hippocampal microglia associated with a concomitant up-regulation of Toll-like receptor (TLR4) in pyramidal and hilar neurons. This, in turn, was associated with a significant reduction of the dendritic hyperpolarization-activated cyclic-AMP gated channel type 1 (HCN1) protein level while Kv4.2 channels were unaltered as assessed by western blot. Immunohistochemistry confirmed the HCN1 decrease in CA1 pyramidal neurons and showed that these changes were associated with a reduction of TRIP8b, an auxiliary subunit for HCN channels implicated in channel subcellular localization and trafficking. At the physiological level, this effect translated into a 50% decrease in HCN1-mediated currents (Ih) measured in the distal dendrites of hippocampal CA1 pyramidal cells. At the functional level, the band-pass filtering properties of dendrites in the theta frequency range (4-12 Hz) and their temporal summation properties were compromised. We conclude that neuroinflammation can independently trigger an acquired channelopathy in CA1 pyramidal cell dendrites that alters their integrative properties. By directly changing cellular function, this phenomenon may participate in the phenotypic expression of various brain diseases.

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Section: Introductionmentioning

confidence: 99%

Neuroinflammation Alters Integrative Properties of Rat Hippocampal Pyramidal Cells

et al. 2018

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“…Neuropathic pain and inflammatory pain (as well as other painful syndromes comprised within the concept of pathological pain) are a frequent source of chronic pain, which causes several significant changes in the CNS, inducing neural plasticity of the areas involved in the processing of pain. Following traumatic injuries, both the neural plasticity of the spinal cord (Dickenson et al, 2002;Ro and Chang, 2005;Baron, 2009;Jarvis and Boyce-Rustay, 2009;Wrigley et al, 2009;Vranken, 2009Vranken, , 2012Boadas-Vaello et al, 2016) and ascending and descending pathways (Ro and Chang, 2005;Baron, 2009;Boadas-Vaello et al, 2016) have been thoroughly reviewed. On another note, the neural plasticity of the spinal cord after inflammatory pain has also been reviewed (Brierley and Linden, 2014;Demir et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Neuroplasticity of Supraspinal Structures Associated with Pathological Pain

Boadas-Vaello

Homs

Reina

et al. 2017

The Anatomical Record

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Peripheral nerve and spinal cord injuries, along with other painful syndromes such as fibromyalgia, diabetic neuropathy, chemotherapeutic neuropathy, trigeminal neuralgia, complex regional pain syndrome, and/or irritable bowel syndrome, cause several neuroplasticity changes in the nervous system along its entire axis affecting the different neuronal nuclei. This paper reviews these changes, focusing on the supraspinal structures that are involved in the modulation and processing of pain, including the periaqueductal gray matter, red nucleus, locus coeruleus, rostral ventromedial medulla, thalamus, hypothalamus, basal ganglia, cerebellum, habenula, primary, and secondary somatosensory cortex, motor cortex, mammillary bodies, hippocampus, septum, amygdala, cingulated, and prefrontal cortex. Hyperexcitability caused by the modification of postsynaptic receptor expression, central sensitization, and potentiation of presynaptic delivery of neurotransmitters, as well as the reduction of inhibitory inputs, changes in dendritic spine, neural circuit remodeling, alteration of gray matter, and upregulation of proinflammatory mediators (e.g., cytokines) by reactivation of astrocytes and microglial cells are the main functional, structural, and molecular neuroplasticity changes observed in the above supraspinal structures, associated with pathological pain. Studying these changes in greater depth may lead to the implementation and improvement of new therapeutic strategies against pathological pain. Anat Rec, 300:1481-1501, 2017. © 2017 Wiley Periodicals, Inc.

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“…Neuropathic pain is characterized by molecular and biochemical neuroplasticity that could occur in the ascending and descending pathways. 4 Considering the time course of evaluating histological sections, Pagano et al 30 have chosen to evaluate GAD expression after 1 hour based on the peaks of expression of transcription factor proteins. 12 On the other hand, microdialysis enables immediate and local sampling and collection of GABA from the interstitial space.…”

Section: Discussionmentioning

confidence: 99%

“…In the CCI rats, peripheral neuropathy promoted mechanical hyperalgesia compared with the control rats (interaction F (1,4) = 51.22; p < 0.05) ( Fig. 3).…”

Section: Mcs Effect On the Nociceptive Thresholdmentioning

confidence: 91%

Neurochemical effects of motor cortex stimulation in the periaqueductal gray during neuropathic pain

Andrade

Martinez

Pagano

et al. 2020

Journal of Neurosurgery

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OBJECTIVEMotor cortex stimulation (MCS) is a neurosurgical technique used to treat patients with refractory neuropathic pain syndromes. MCS activates the periaqueductal gray (PAG) matter, which is one of the major centers of the descending pain inhibitory system. However, the neurochemical mechanisms in the PAG that underlie the analgesic effect of MCS have not yet been described. The main goal of this study was to investigate the neurochemical mechanisms involved in the analgesic effect induced by MCS in neuropathic pain. Specifically, we investigated the release of γ-aminobutyric acid (GABA), glycine, and glutamate in the PAG and performed pharmacological antagonism experiments to validate of our findings.METHODSMale Wistar rats with surgically induced chronic constriction of the sciatic nerve, along with sham-operated rats and naive rats, were implanted with both unilateral transdural electrodes in the motor cortex and a microdialysis guide cannula in the PAG and subjected to MCS. The MCS was delivered in single 15-minute sessions. Neurotransmitter release was evaluated in the PAG before, during, and after MCS. Quantification of the neurotransmitters GABA, glycine, and glutamate was performed using a high-performance liquid chromatography system. The mechanical nociceptive threshold was evaluated initially, on the 14th day following the surgery, and during the MCS. In another group of neuropathic rats, once the analgesic effect after MCS was confirmed by the mechanical nociceptive test, rats were microinjected with saline or a glycine antagonist (strychnine), a GABA antagonist (bicuculline), or a combination of glycine and GABA antagonists (strychnine+bicuculline) and reevaluated for the mechanical nociceptive threshold during MCS.RESULTSMCS reversed the hyperalgesia induced by peripheral neuropathy in the rats with chronic sciatic nerve constriction and induced a significant increase in the glycine and GABA levels in the PAG in comparison with the naive and sham-treated rats. The glutamate levels remained stable under all conditions. The antagonism of glycine, GABA, and the combination of glycine and GABA reversed the MCS-induced analgesia.CONCLUSIONSThese results suggest that the neurotransmitters glycine and GABA released in the PAG may be involved in the analgesia induced by cortical stimulation in animals with neuropathic pain. Further investigation of the mechanisms involved in MCS-induced analgesia may contribute to clinical improvements for the treatment of persistent neuropathic pain syndromes.

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Neuroplasticity of ascending and descending pathways after somatosensory system injury: reviewing knowledge to identify neuropathic pain therapeutic targets

Cited by 83 publications

References 144 publications

Neuroinflammation Alters Integrative Properties of Rat Hippocampal Pyramidal Cells

Neuroinflammation Alters Integrative Properties of Rat Hippocampal Pyramidal Cells

Neuroplasticity of Supraspinal Structures Associated with Pathological Pain

Neurochemical effects of motor cortex stimulation in the periaqueductal gray during neuropathic pain

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