Abstract
In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain.
Highlights
Parkinson’s disease (PD) is a progressive and incurable neurodegenerative disorder affecting 1% of people over 65 years and recognized clinically by its motor symptoms, such as bradykinesia, rest tremor, rigidity, and postural instability [1,2,3]
Parkinsonian phenotype was validated in 6-OHDA-lesioned rats using tyrosine hydroxylase (TH) quantification and behavioral testing
Western blotting analysis showed that protein level of TH in 6-OHDA-lesioned group significantly decreased in the CPu by 45% compared to the sham group (Figure 1(c), P = 0.0012, n = 4 rats/group)
Summary
Parkinson’s disease (PD) is a progressive and incurable neurodegenerative disorder affecting 1% of people over 65 years and recognized clinically by its motor symptoms, such as bradykinesia, rest tremor, rigidity, and postural instability [1,2,3]. Nonmotor symptoms in PD patients, including neuropsychiatric symptoms, pain, sexual difficulties, sleep disorders, and gastrointestinal symptoms, have been received much more attention, because they significantly reduced quality of life in PD patients if left untreated [4,5,6,7,8]. Pain is a common nonmotor symptom and has a disabling effect on quality of life in PD patients, affecting about 60% to 85% of PD patients [9,10,11,12]. The management of PD-associated pain remains challenging and a major hurdle
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
