Alteration of nociceptive integration in the spinal cord of a rat model of Parkinson's disease

Charles, Keri-Ann; Naudet, Frédéric; Bouali‐Benazzouz, Rabia; Landry, Marc; Deurwaerdère, Philippe De; Fossat, Pascal; Benazzouz, Abdelhamid

doi:10.1002/mds.27377

Cited by 28 publications

(10 citation statements)

References 17 publications

(19 reference statements)

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“…We have previously shown that the PD model induces an increase in c-Fos-positive cells, accompanied by a decrease in opioidergic modulation [ 17 ]. Consistent with our findings, persistent pain in a rat model similar to the one presented in this study was associated with hyperexcitability of nociceptive neurons in the DHSC observed by electrophysiology [ 26 ]. Interestingly, eMCS was able to reverse the c-Fos-positive cells to control levels, suggesting an inhibition in nociceptive neuron activation, as previously shown in naive rats [ 59 ].…”

Section: Discussionsupporting

confidence: 91%

“…Beside dopamine, serotonin deficit also plays a major role in PD pathophysiology and is related to nonmotor symptoms such as pain and depression [ 21 , 22 , 23 , 24 , 25 ]. In rodent PD model, a deficiency in the descending analgesic pathways results in opioidergic deficit, glial activation, and neuronal hyperexcitability in the dorsal horn of the spinal cord (DSHC), leading to increased central sensitization and consequent pain syndrome [ 17 , 25 , 26 ]. Hence, we hypothesized that therapeutic approaches based on the reinforcement of descending analgesic control may be more effective for pain management in PD patients.…”

Section: Introductionmentioning

confidence: 99%

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Motor Cortex Stimulation Reversed Hypernociception, Increased Serotonin in Raphe Neurons, and Caused Inhibition of Spinal Astrocytes in a Parkinson’s Disease Rat Model

Campos

Berzuino

Barbosa

et al. 2021

Cells

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Persistent pain is a prevalent symptom of Parkinson’s disease (PD), which is related to the loss of monoamines and neuroinflammation. Motor cortex stimulation (MCS) inhibits persistent pain by activating the descending analgesic pathways; however, its effectiveness in the control of PD-induced pain remains unclear. Here, we evaluated the analgesic efficacy of MCS together with serotonergic and spinal glial modulation in an experimental PD (ePD) rat model. Wistar rats with unilateral striatal 6-OHDA and MCS were assessed for behavioral immobility and nociceptive responses. The immunoreactivity of dopamine in the substantia nigra and serotonin in the nucleus raphe magnus (NRM) and the neuronal, astrocytic, and microglial activation in the dorsal horn of the spinal cord were evaluated. MCS, without interfering with dopamine loss, reversed ePD-induced immobility and hypernociception. This response was accompanied by an exacerbated increase in serotonin in the NRM and a decrease in neuronal and astrocytic hyperactivation in the spinal cord, without inhibiting ePD-induced microglial hypertrophy and hyperplasia. Taken together, MCS induces analgesia in the ePD model, while restores the descending serotonergic pathway with consequent inhibition of spinal neurons and astrocytes, showing the role of MCS in PD-induced pain control.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Motor Cortex Stimulation Reversed Hypernociception, Increased Serotonin in Raphe Neurons, and Caused Inhibition of Spinal Astrocytes in a Parkinson’s Disease Rat Model

Campos

Berzuino

Barbosa

et al. 2021

Cells

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“…At the behavioral level, regardless inconsistencies found through the scientific publications, p a r k i n s o n i a n a n i m a l s t e n d t o m i m i c t h e h u m a n symptomatology showing motor but also non-motor impairments (Titova et al, 2017). An array of studies report that rodents lesioned with 6-OHDA or MPTP show anxious and depressive behavior, pain, cognitive, and sleep disturbances (Monaca et al, 2004;Pérez et al, 2009;Berghauzen-Maciejewska et al, 2014;Vo et al, 2014;Kamińska et al, 2017;Charles et al, 2018;Campos et al, 2019;Domenici et al, 2019), more notably in bilateral models of the disease (Ferro et al, 2005;Tadaiesky et al, 2008;Santiago et al, 2010;Bonito-Oliva et al, 2014;Vieira et al, 2019). Although the participation of other nuclei cannot be ruled out, the role of the LC in the mentioned functions is widely accepted.…”

Section: Preclinical Evidencementioning

confidence: 99%

The Noradrenergic System in Parkinson’s Disease

et al. 2020

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Nowadays it is well accepted that in Parkinson's disease (PD), the neurodegenerative process occurs in stages and that damage to other areas precedes the neuronal loss in the substantia nigra pars compacta, which is considered a pathophysiological hallmark of PD. This heterogeneous and progressive neurodegeneration may explain the diverse symptomatology of the disease, including motor and non-motor alterations. In PD, one of the first areas undergoing degeneration is the locus coeruleus (LC). This noradrenergic nucleus provides extensive innervation throughout the brain and plays a fundamental neuromodulator role, participating in stress responses, emotional memory, and control of motor, sensory, and autonomic functions. Early in the disease, LC neurons suffer modifications that can condition the effectiveness of pharmacological treatments, and importantly, can lead to the appearance of common non-motor symptomatology. The noradrenergic system also exerts anti-inflammatory and neuroprotective effect on the dopaminergic degeneration and noradrenergic damage can consequently condition the progress of the disease. From the pharmacological point of view, it is also important to understand how the noradrenergic system performs in PD, since noradrenergic medication is often used in these patients, and drug interactions can take place when combining them with the gold standard drug therapy in PD, L-3,4-dihydroxyphenylalanine (L-DOPA). This review provides an overview about the functional status of the noradrenergic system in PD and its contribution to the efficacy of pharmacologicalbased treatments. Based on preclinical and clinical publications, a special attention will be dedicated to the most prevalent non-motor symptoms of the disease.

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“…This is consistent with the analgesic benefits provided by oxycodone/naloxone in PD patients with severe pain 25,27 and is further supported by the findings of bilateral reductions in enkephalins and μ-opioid receptors and increased excitability of lamina V wide dynamic range neurons in the spinal cord of unilaterally 6-OHDA lesioned rats which expressed mechanical and heat hypersensitivity. 68,76 Serotonergic involvement in the nociceptive hypersensitivity is also implicated. For example, 6-OHDA lesioned rats with nociceptive hypersensitivity show reduced numbers of 5-HT neurons in the rostral ventromedial medulla (RVM) and in the dorsal horn of the spinal cord, 77 suggestive of reduced 5-HT transmission in these pain related regions.…”

Section: -Ohdamentioning

confidence: 99%

Potential of animal models for advancing the understanding and treatment of pain in Parkinson’s disease

Buhidma

Rukavina

Chaudhuri

et al. 2020

npj Parkinsons Dis.

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Pain is a commonly occurring non-motor symptom of Parkinson's disease (PD). Treatment of pain in PD remains less than optimal and a better understanding of the underlying mechanisms would facilitate discovery of improved analgesics. Animal models of PD have already proven helpful for furthering the understanding and treatment of motor symptoms of PD, but could these models offer insight into pain in PD? This review addresses the current position regarding pain in preclinical models of PD, covering the face and predictive validity of existing models and their use so far in advancing understanding of the mechanisms contributing to pain in PD. While pain itself is not usually measured in animals, nociception in the form of thermal, mechanical or chemical nociceptive thresholds offers a useful readout, given reduced nociceptive thresholds are commonly seen in PD patients. Animal models of PD including the reserpine-treated rat and neurodegenerative models such as the MPTP-treated mouse and 6hydroxydopamine (6-OHDA)-treated rat each exhibit reduced nociceptive thresholds, supporting face validity of these models. Furthermore, some interventions known clinically to relieve pain in PD, such as dopaminergic therapies and deep brain stimulation of the subthalamic nucleus, restore nociceptive thresholds in one or more models, supporting their predictive validity. Mechanistic insight gained already includes involvement of central and spinal dopamine and opioid systems. Moving forward, these preclinical models should advance understanding of the cellular and molecular mechanisms underlying pain in PD and provide test beds for examining the efficacy of novel analgesics to better treat this debilitating non-motor symptom.

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Alteration of nociceptive integration in the spinal cord of a rat model of Parkinson's disease

Abstract: These results provide evidence for alteration of nociceptive integration in the spinal dorsal horn neurons in 6-OHDA rats that can reflect changes in pain behavior. © 2018 International Parkinson and Movement Disorder Society.

Cited by 28 publications

References 17 publications

Motor Cortex Stimulation Reversed Hypernociception, Increased Serotonin in Raphe Neurons, and Caused Inhibition of Spinal Astrocytes in a Parkinson’s Disease Rat Model

Motor Cortex Stimulation Reversed Hypernociception, Increased Serotonin in Raphe Neurons, and Caused Inhibition of Spinal Astrocytes in a Parkinson’s Disease Rat Model

The Noradrenergic System in Parkinson’s Disease

Potential of animal models for advancing the understanding and treatment of pain in Parkinson’s disease

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