Neural mechanism underlying hyperalgesic response to orofacial pain in Parkinson's disease model rats

Maegawa, Hiroharu; Morimoto, Yoshinari; Kudo, Chiho; Hanamoto, Hiroshi; Sato, Aiji; Sugimura, Mitsutaka; Kato, Takafumi; Yoshida, Atsushi; Niwa, Hitoshi

doi:10.1016/j.neures.2015.01.006

Cited by 25 publications

(38 citation statements)

References 56 publications

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“…Intranigral microinjection of naloxone has suppressed the antinociceptive effects of systemically administered morphine in thermal nociceptive tests in a dose-related manner (Baumeister et al, 1988). Hypersensitivity to noxious stimulation has also been reported to possibly be involved in unilateral dopamine depletion in the nigrostriatal pathway in the rat (Maegawa et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Differential Spinal and Supraspinal Activation of Glia in a Rat Model of Morphine Tolerance

et al. 2018

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Development of tolerance is a well known pharmacological characteristic of opioids and a major clinical problem. In addition to the known neuronal mechanisms of opioid tolerance, activation of glia has emerged as a potentially significant new mechanism. We studied activation of microglia and astrocytes in morphine tolerance and opioid-induced hyperalgesia in rats using immunohistochemistry, flow cytometry and RNA sequencing in spinal- and supraspinal regions. Chronic morphine treatment that induced tolerance and hyperalgesia also increased immunoreactivity of spinal microglia in the dorsal and ventral horns. Flow cytometry demonstrated that morphine treatment increased the proportion of M2-polarized spinal microglia, but failed to impact the number or the proportion of M1-polarized microglia. In the transcriptome of microglial cells isolated from the spinal cord (SC), morphine treatment increased transcripts related to cell activation and defense response. In the studied brain regions, no activation of microglia or astrocytes was detected by immunohistochemistry, except for a decrease in the number of microglial cells in the substantia nigra. In flow cytometry, morphine caused a decrease in the number of microglial cells in the medulla, but otherwise no change was detected for the count or the proportion of M1- and M2-polarized microglia in the medulla or sensory cortex. No evidence for the activation of glia in the brain was seen. Our results suggest that glial activation associated with opioid tolerance and opioid-induced hyperalgesia occurs mainly at the spinal level. The transcriptome data suggest that the microglial activation pattern after chronic morphine treatment has similarities with that of neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Differential Spinal and Supraspinal Activation of Glia in a Rat Model of Morphine Tolerance

et al. 2018

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“…We assumed that the effects of 6-OHDA on GABA were likely indirect via PICs signal. In addition, the previous studies have demonstrated that dopamine levels were decreased in SNc by 6-OHDA ( 31 ). Thus, we did not perform the immunohistochemical experiment to indicate this result in our current study.…”

Section: Discussionmentioning

confidence: 95%

“…It has been reported that 6-OHDA injected into the medial forebrain bundle of rats to lead to extensive destruction of DA neurons of the substantia nigra pars compacta ( 29 ). A unilateral lesion of the nigrostriatal pathway also causes rotational behavior toward the lesioned side after administration of methamphetamine ( 30 , 31 ). In the present study, the same rat model of PD was used, and consistent with prior studies, we have observed that rotational behavior appeared >7 turns/min after methamphetamine in 6-OHDA-injected rats.…”

Section: Discussionmentioning

confidence: 99%

“…Early studies showed that electrical stimulation or opioids microinjected into the PAG produced profound long-lasting antinociception ( 32 , 33 ). In particular, activated neuronal cells are identified in PAG of PD rats evoked by 6-OHDA ( 31 ), suggesting that neural substrates are likely present within the PAG in engagement of the abnormalities in pain response observed in PD. Furthermore, previous studies showed that PIC mediators appear in the PAG, and activation of PICs in the PAG plays a role in modulating pain response or is involved in morphine withdrawal response ( 34 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

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Contribution of Pro-inflammatory Cytokine Signaling within Midbrain Periaqueductal Gray to Pain Sensitivity in Parkinson’s Disease via GABAergic Pathway

et al. 2016

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Background/aimsHypersensitive pain response is often observed in patients with Parkinson’s disease (PD); however, the mechanisms responsible for hyperalgesia are not well understood. Chronic neuroinflammation is one of the hallmarks of PD pathophysiology. Since the midbrain periaqueductal gray (PAG) is an important component of the descending inhibitory pathway controlling on central pain transmission, we examined the role for pro-inflammatory cytokines (PICs) system of PAG in regulating exaggerated pain evoked by PD.MethodsWe used a rat model of PD to perform the experimental protocols. PD was induced by microinjection of 6-hydroxydopamine to lesion the left medial forebrain bundle. Pain responses to mechanical and thermal stimulation were first examined in control rats and PD rats. Then, ELISA and Western Blot analysis were used to determine PIC levels and their receptors expression.ResultsProtein expression of IL-1β, IL-6, and TNF-α receptors (namely, IL-1R, IL-6R, and TNFR subtype TNFR1) in the plasma membrane PAG of PD rats was upregulated, whereas the total expression of PIC receptors was not significantly altered. The ratio of membrane protein and total protein (IL-1R, IL-6R, and TNFR1) was 1.48 ± 0.15, 1.59 ± 0.18, and 1.67 ± 0.16 in PAG of PD rats (P < 0.05 vs. their respective controls). This was accompanied with increases of PICs of PAG and decreases of GABA (623 ± 21 ng/mg in control rats and 418 ± 18 ng/mg in PD rats; P < 0.05 vs. control rats) and withdrawal thresholds to mechanical and thermal stimuli. Our data further showed that the concentrations of GABA and withdrawal thresholds were largely restored by blocking those PIC receptors in PAG of PD rats. Stimulation of GABA receptors in PAG of PD rats also blunted a decrease in withdrawal thresholds.ConclusionOur data suggest that upregulation of the membrane PIC receptor in the PAG of PD rats is likely to impair the descending inhibitory pathways in regulating pain transmission and thereby plays a role in the development of hypersensitive pain response in PD.

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“…It determined by the chronic and slowly progressive injury and depletion of dopaminergic neurons in the substantia nigra that may led to motor disturbances, including bradykinesia, akinesia, rest tremor, and postural instability. Likewise, patients may suffer from nonmotor symptoms, including depression, anxiety, rapid eye movement (REM) disorder, and pain [2,3]. Catalepsy, the impairment of movement initiation, is an extrapyramidal dysfunction known as a prominent motor symptom of PD, which is related to the striatal dopamine reduction.…”

Section: Introductionmentioning

confidence: 99%

The Cataleptic, Asymmetric, Analgesic, and Brain Biochemical Effects of Parkinson’s Disease Can Be Affected byToxoplasma gondiiInfection

Taherianfard

Riyahi

Razavi

et al. 2020

BioMed Research International

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Purpose. Parkinson’s disease (PD) is a neurodegenerative disorder with progressive motor defects. Therefore, the aim of the present investigation was to examine whether catalepsy, asymmetry, and nociceptive behaviors; the Nissl-body and neuron distribution; brain-derived neurotrophic factor (BDNF); malondialdehyde (MDA); total antioxidant capacity (TAC) levels; and the percentage of dopamine depletion of striatal neurons in the rat model of Parkinson’s disease (PD) can be affected by Toxoplasma gondii (TG) infection. Methods. Fifty rats were divided into five groups: control (intact rats), sham (rats which received an intrastriatal injection of artificial cerebrospinal fluid (ACSF)), PD control (induction of PD without TG infection), TG control (rats infected by TG without PD induction), and PD infected (third week after PD induction, infection by TG was done). PD was induced by the unilateral intrastriatal microinjection of 6-hydroxydopamine (6-OHDA) and ELISA quantified dopamine, BDNF, MDA, and TAC in the striatum tissue. Cataleptic, asymmetrical, nociceptive, and histological alterations were determined by bar test, elevated body swing test, formalin test, and Nissl-body and neuron counting in the striatal neurons. Results. The results demonstrated that PD could significantly increase the number of biased swings, descent latency time, and nociceptive behavior and decrease the distribution of Nissl-stained neurons compared to the control and sham groups. TG infection significantly improved biased swing, descent latency time, nociceptive behavior, and the Nissl-body distribution in striatal neurons in comparison to the PD control group. The striatal level of BDNF in the PD-infected and TG control groups significantly increased relative to the PD control group. The striatal MDA was significantly higher in the PD control than other groups, while striatal TAC was significantly lower in the PD control than other groups. Conclusions. The current study indicates that TG infection could improve the cataleptic, asymmetric, nociceptive and behaviors; the level of striatal dopamine release; BDNF levels; TAC; and MDA in PD rats.

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Neural mechanism underlying hyperalgesic response to orofacial pain in Parkinson's disease model rats

Cited by 25 publications

References 56 publications

Differential Spinal and Supraspinal Activation of Glia in a Rat Model of Morphine Tolerance

Differential Spinal and Supraspinal Activation of Glia in a Rat Model of Morphine Tolerance

Contribution of Pro-inflammatory Cytokine Signaling within Midbrain Periaqueductal Gray to Pain Sensitivity in Parkinson’s Disease via GABAergic Pathway

The Cataleptic, Asymmetric, Analgesic, and Brain Biochemical Effects of Parkinson’s Disease Can Be Affected byToxoplasma gondiiInfection

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