Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson’s disease
In Parkinson’s disease (PD), chronic pain is a common symptom which markedly affects the quality of life. Some physiological arguments proposed that Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in PD.
We investigated in 58 PD patients the effect of STN-DBS on pain using the short McGill Pain Questionnaire and other pain parameters such as the Bodily discomfort subscore of the Parkinson’s disease Questionnaire 39 and the Unified Parkinson's Disease Rating Scale section II (UPDRS II) item 17.
All pain scores were significantly improved 12 months after STN-DBS. This improvement was not correlated with motor improvement, depression scores or L-Dopa reduction.
STN-DBS induced a substantial beneficial effect on pain in PD, independently of its motor effects and mood status of patients.
Available from: Xianguo Liu
- "This is in line with the finding that injury to motor neurons produces neuropathic pain in rats, although the situation in postpoliomyelitis patients might be more complicated. Furthermore, pain also constitutes the major non motor syndrome in Parkinson's disease (PD) (Dieb et al., 2014; Pellaprat et al., 2014). In our recent work, we have found that L5-VRT up-regulates interleukin-6 (IL-6) in uninjured primary afferent system, and that the absence of IL-6 achieved by pre-treatment with IL-6 neutralizing antibody delays the induction of mechanical allodynia in bilateral hindpaws (Wei et al., 2013a). "
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ABSTRACT: Motor nerve injury by L5 ventral root transection (L5-VRT) initiates interleukin-6 (IL-6) up-regulation in primary afferent system contributing to neuropathic pain. However, the early upstream regulatory mechanisms of IL-6 after L5-VRT are still unknown. Here, we monitored both the activity of calpain, a calcium-dependent protease suggested as one of the earliest mediators for cytokine regulation, and the expression of IL-6 in bilateral L4-L6 dorsal root ganglias (DRGs) soon after L5-VRT. We found that the protein level of calpain-2 in DRGs, but not calpain-1 was increased transiently in the first 10 min-1 h ipsilaterally and 20 min-1h contralaterally after L5-VRT, long before mechanical allodynia was initiated (5-15 h ipsilaterally and 15 h-1 d contralaterally). The early activation of calpain evaluated by the generation of spectrin breakdown products (SBDP) correlated well with IL-6 up-regulation in bilateral DRGs. Double immunofluorescence staining revealed that almost all the calpain-2 positive neurons expressed IL-6, indicating an association between calpain-2 and IL-6. Inhibition of calpain by pre-treatment with MDL28170 (25mg/kg, i.p.) attenuated the rat mechanical allodynia and prevented the early up-regulation of IL-6 following L5-VRT. Addition of exogenous calpain-2 onto the surface of left L5 DRG triggered a temporal allodynia and increased IL-6 in bilateral DRGs simultaneously. Taken together, the early increase of calpain-2 in L5-VRT rats might be responsible for the induction of allodynia via up-regulating IL-6 in DRG neurons.
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ABSTRACT: Recently, we demonstrated that dimeric apocynin prevented loss of motor function in the leucine-rich repeat kinase 2 (LRRK2(R1441G)) transgenic (tg) mouse (treated with 200mg/kg, three times per week) [B.P. Dranka et al., Neurosci. Lett. 549 (2013) 57-62]. Here we extend those studies by treating LRRK2(R1441G) mice with an orally-available, mitochondrially-targeted apocynin derivative. We hypothesized that the increased mitochondrial permeability of Mito-apocynin, due to the triphenylphosphonium moiety, would allow improvement of Parkinson's disease (PD) symptoms at lower doses than those required for diapocynin. Tests of motor coordination (pole test, Rotor-Rod) revealed a significant deficit in coordinated motor function in LRRK2(R1441G) mice by 15 months of age. Decreased performance on the pole test and Rotor-Rod in the LRRK2(R1441G) mice was prevented with Mito-apocynin treatment (3mg/kg, three times per week). Decreased olfactory function is an early indication of PD in human patients. LRRK2(R1441G) tg mice displayed deficits in sense of smell in both the hidden treat test, and a radial arm maze test. Interestingly, treatment with Mito-apocynin prevented this hyposmia, and animals retained normal ability to identify either a scented treat or a food pellet as well as wild type littermates. Together, these data demonstrate that the mitochondria-targeted apocynin analog is effective in preventing early PD-like symptoms in the LRRK2(R1441G) mouse model.
Available from: Chae S Lim
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ABSTRACT: Pain is the most prominent non-motor symptom observed in patients with Parkinson's disease (PD). However, the mechanisms underlying the generation of pain in PD have not been well studied. We used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD to analyze the relationship between pain sensory abnormalities and the degeneration of dopaminergic neurons.
The latency to fall off the rotarod and the total distance traveled in round chamber were significantly reduced in MPTP-induced PD mice, consistent with motor dysfunction. MPTP-treated mice also showed remarkably shorter nociceptive response latencies compared to saline-treated mice and the subcutaneous injection of L-3,4-dihydroxyphenylalanine (L-DOPA) partially reversed pain hypersensitivity induced by MPTP treatment. We found that degeneration of cell bodies and fibers in the substantia nigra pars compacta and the striatum of MPTP-treated mice. In addition, astrocytic and microglial activation was seen in the subthalamic nucleus and neuronal activity was significantly increased in the striatum and globus pallidus. However, we did not observe any changes in neurons, astrocytes, and microglia of both the dorsal and ventral horns in the spinal cord after MPTP treatment.
These results suggest that the dopaminergic nigrostriatal pathway may have a role in inhibiting noxious stimuli, and that abnormal inflammatory responses and neural activity in basal ganglia is correlated to pain processing in PD induced by MPTP treatment.
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