PD-related Pain Research Articles

Pain Assessment in Chinese Parkinson’s Disease Patients Using King’s Parkinson’s Disease Pain Scale

PurposeTo assess Parkinson’s disease (PD)-related pain using the Chinese translation of King’s Parkinson’s disease Pain Scale (KPPS).Patients and MethodsA cohort of 200 patients with primary PD was recruited for this study. Their demographic and clinical features, including age, disease duration, levodopa equivalent daily dose (LEDD), and scores on the Unified Parkinson’s Disease Rating Scale-III (UPDRS III), Hoehn-Yahr Scale (H&Y), Mini-Mental State Examination (MMSE), Activities of Daily Living Scale (ADL), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Pittsburgh Sleep Quality Index (PSQI), Visual Analogue Scale (VAS) and KPPS, were recorded.ResultsThe prevalence of PD-related pain was 44.5%. Among the patients with PD-related pain, the average KPPS score was 41.2 ± 26.8. Pain was most commonly located in the lower limbs (60.7%), upper limbs (22.5%) and waist (21.3%). The most common pain type was musculoskeletal pain (68.5%). Compared with the PD group without pain, the PD group with pain had a longer disease duration (p = 0.022), higher LEDD (p = 0.008), higher UPDRSIII score (p = 0.018), higher H&Y stage (p = 0.003), higher HAMD score (p < 0.001), higher HAMA score (p < 0.001), lower ADL score (p = 0.046) and higher PSQI score (p < 0.001). PD-related pain was correlated with the H&Y stage and the PSQI score (p < 0.05). Cut-off points of 0, 34, and 70 were obtained to discriminate pain severity levels between no pain, mild, moderate, and severe pain, respectively.ConclusionChinese version of KPPS is not only an easy tool for characterization and scoring of pain in PD patients but also has the ability to distinguish between different levels of pain severity.

Efficacy and safety evaluation of safinamide as an add-on treatment to levodopa for parkinson’s disease

ABSTRACT Introduction While levodopa is still the most effective treatment for Parkinson’s disease, concerns about long-term complications such as wearing-off and dyskinesia with levodopa usage remain. Areas covered Safinamide is a highly selective and reversible monoamine oxidase B inhibitor introduced in the European Union, Japan, and the United States as an adjunctive agent to levodopa in PD patients with motor fluctuation. This review outlines the pharmacological properties, therapeutic effects, and tolerability of safinamide as an adjunct to levodopa in patients with advanced PD. Efficacy and safety findings from double-blind and placebo-controlled clinical trials for safinamide as an adjunct therapy to levodopa for PD are summarized. Expert opinion Safinamide was well tolerated as a treatment for PD, and there was no significant difference in the frequency and severity of adverse events between the safinamide and placebo groups. It was also suggested that safinamide had a beneficial effect on the accompanying non-motor symptoms such as PD-related pain. Safinamide may exhibit neuroprotective effects through antioxidant and anti-glutamate effects, and research on the disease-modifying effect of PD is desired in the future.

Characteristics and treatment of pain in Parkinson's disease

Pain is a representative non-motor symptom in patients with Parkinson's disease (PD). Pain is one of the most common symptoms that plague patients with PD regardless of the stage of the disease, also it can exacerbate other symptoms, such as depression, anxiety or sleep disturbance, and lead to impaired quality of life. However, pain is often not adequately evaluated and treated. PD patients complain of a wide variety of pain, including both PD-related pain which caused by PD-specific symptoms, for example, rigidity, bradykinesia or motor fluctuation, and PD-unrelated pain, and it can be divided into central and peripheral depending on the site of the disorder. In the medical care of the pain, it is important to evaluate the type and severity of the pain using PD-specific assessment scales such as King's PD pain scale and to consider the evidence-based treatment methods according to the pathophysiology of the pain.

Neuronal Dynamics of Pain in Parkinson's Disease.

Pain is an important non-motor symptom of Parkinson’s disease (PD). It negatively impacts the quality of life. However, the pathophysiological mechanisms underlying pain in PD remain to be elucidated. This study sought to use electroencephalographic (EEG) coherence analysis to compare neuronal synchronization in neuronal networks between patients with PD, with and without pain. Twenty-four patients with sporadic PD were evaluated for the presence of pain. Time-frequency and coherence analyses were performed on their EEG data. Whole-brain and regional coherence were calculated and compared between pain-positive and pain-negative patients. There was no significant difference in the whole-brain coherence between the pain-positive and pain-negative groups. However, temporal–temporal coherence differed significantly between the two groups (p = 0.031). Our findings indicate that aberrant synchronization of inter-temporal regions is involved in PD-related pain. This will further our understanding of the mechanisms underlying pain in PD.

Pain in Parkinson's disease: Mechanism-based treatment strategies.

Chronic pain, highly prevalent throughout the course of Parkinson's disease (PD), has been ranked as one of the top ten most bothersome symptoms people with Parkinson's (PwP) are experiencing. Yet, robust evidence-based treatment strategies are lacking. This unmet need is partly attributable to the multifaceted nature of PD-related pain, which results in part from a complex and poorly understood interplay involving a range of neurotransmitter pathways. Degeneration of nigrostriatal dopaminergic pathways and alterations of central nervous system extra-striatal dopaminergic, noradrenergic, serotoninergic, glutamatergic, opioidergic and endocannabinoid circuits may all promote a heightened experience of pain in PwP. Thus, the potential targets for mechanism-based pain-relieving strategies in PwP are several. These targets are discussed herein. An increasing number of clinical trials and experimental studies in animal models of PD are being designed with the aim of addressing the pathophysiological mechanism(s) underlying PD-related pain. Overall, recent research findings highlight the analgesic effects of dopaminergic and opioidergic medication for certain subtypes of pain in PwP, whereas proposing novel strategies that involve targeting other neurotransmitter pathways. The origin of pain in PwP remains under investigation. Although our understanding of the mechanisms underpinning persistent pain in PD has improved in recent years, this has not yet translated to clinical alleviation of this most troublesome nonmotor symptom. Patient stratification linked with evidence-based personalized pain-treatment plans for optimal analgesic relief will rely on advances in our understanding of the dopaminergic and nondopaminergic targets outlined in this review.

Increased plasma orexin-A concentrations are associated with the non-motor symptoms in Parkinson’s disease patients

BackgroundOrexin, a neuropeptide primarily secreted by neurons in the lateral hypothalamus, has been implicated in Parkinson’s disease (PD). Studies on the relationship between plasma orexin-A levels and PD are rare. ObjectivesThis study aimed to assess levels of plasma orexin-A in the progression of PD and to evaluate the correlation between orexin-A levels and non-motor symptoms. MethodsEnzyme-linked immunosorbent assay was used to determine plasma orexin-A levels in 117 healthy controls and 121 PD patients, including those with early (n = 68), medium (n = 40) and advanced (n = 13) stages of the disease. Evaluation of motor symptoms and non-motor symptoms in PD patients, such as sleep disorders, cognitive dysfunction, neuropsychiatric symptoms, autonomic nervous dysfunction, hyposmia and PD-related pain, were assessed by the associated scales. ResultsPlasma orexin-A levels were significantly higher in PD patients compared to healthy controls. Orexin-A levels were elevated in early-stage and medium-stage PD compared to healthy controls, but were decreased in advanced-stage PD. Orexin-A levels were negatively correlated with the Unified Parkinson’s Disease Rating Scale Part III scores, disease duration, and dopamine receptor agonist doses, and were positively correlated with the Pittsburgh Sleep Quality Index, REM-sleep Behavior Disorder Questionnaire, 14-item Hamilton Anxiety Scale, Mini-Mental State Examination, and Non-motor Symptom Scale items 22–24 scores. ConclusionsWe found for the first time that plasma orexin-A levels were increased in early-stage and medium-stage PD and were decreased in advanced-stage PD. Furthermore, orexin-A levels were correlated with the non-motor symptoms of insomnia, REM-sleep behavior disorder, anxiety, cognitive dysfunction, and renal dysfunction.

The Parkinson disease pain classification system: results from an international mechanism-based classification approach.

Pain is a common nonmotor symptom in patients with Parkinson disease (PD) but the correct diagnosis of the respective cause remains difficult because suitable tools are lacking, so far. We developed a framework to differentiate PD- from non-PD-related pain and classify PD-related pain into 3 groups based on validated mechanistic pain descriptors (nociceptive, neuropathic, or nociplastic), which encompass all the previously described PD pain types. Severity of PD-related pain syndromes was scored by ratings of intensity, frequency, and interference with daily living activities. The PD-Pain Classification System (PD-PCS) was compared with classic pain measures (ie, brief pain inventory and McGill pain questionnaire [MPQ], PDQ-8 quality of life score, MDS-UPDRS scores, and nonmotor symptoms). 159 nondemented PD patients (disease duration 10.2 ± 7.6 years) and 37 healthy controls were recruited in 4 centers. PD-related pain was present in 122 patients (77%), with 24 (15%) suffering one or more syndromes at the same time. PD-related nociceptive, neuropathic, or nociplastic pain was diagnosed in 87 (55%), 25 (16%), or 35 (22%), respectively. Pain unrelated to PD was present in 35 (22%) patients. Overall, PD-PCS severity score significantly correlated with pain's Brief Pain Inventory and MPQ ratings, presence of dyskinesia and motor fluctuations, PDQ-8 scores, depression, and anxiety measures. Moderate intrarater and interrater reliability was observed. The PD-PCS is a valid and reliable tool for differentiating PD-related pain from PD-unrelated pain. It detects and scores mechanistic pain subtypes in a pragmatic and treatment-oriented approach, unifying previous classifications of PD-pain.

Contribution of functional dopamine D2 and D3 receptor variants to motor and non-motor symptoms of early onset Parkinson’s disease

In the present study, we focused on investigating the contribution of functional dopamine D2 and D3 receptor variants to motor and/or non-motor symptoms of early onset Parkinson’s disease (EOPD). Three functional single nucleotide polymorphisms (SNPs), DRD3 rs6280, DRD2 rs2283265 and DRD2 rs1076560, were genotyped in 128 Turkish EOPD patients and then, statistical analysis was conducted for the potential impacts of SNPs on clinical parameters. All three SNPs were found to be statistically significant in terms of PD-related pain: DRD3 [rs6280; risk allele “T” for pain; p = 0.031; odds ratio (OR)=4.25], DRD2 [rs2283265; risk allele “A” for pain; p = 0.001; OR=8.47] and, DRD2 [rs1076560; risk allele “A” for pain; p = 0.022; OR=4.58]. Additionally, bilateral disease [p = 0.011; OR=5.10] and gender [risk group “female”; p = 0.003; OR=8.53] were also identified as significant univariate risk factors for PD-related pain. Based on logistic regression analysis conducted with the significant univariate risk factors, this the first report to clarify that a female patient with bilateral PD and DRD2 rs2283265 polymorphism has a significant risk for PD-related pain. Our findings might contribute to improve life quality by offering treatment options for pain in PD patients with these clinical and genetic features.

Short-term effect of deep brain stimulation on pain associated with Parkinson′s disease

Objective To investigate the short-term outcome of deep brain stimulation (DBS) for the treatment of pain associated with PD (Parkinson′s disease). Methods The clinical data of 47 cases of PD patients with pain symptoms admitted to Neurosurgery Department of Northern Theater Command General Hospital from January 2017 to June 2018 were retrospectively analyzed. A total of 35 patients underwent STN (subthalamic nucleus)-DBS and 12 patients underwent GPi (globus pallidus internus)-DBS. The stimulation contact selection and parameter adjustment were carried out at 3 weeks post operation. Visual analogue scale (VAS) was used to evaluate the degree of preoperative and postoperative pain severity. Results The VAS [median (upper and lower quartiles)] were 1.0 (0.5-1.4) and 1.0(0.7-1.6) respectively at 3 months and 6 months post operation in 47 patients, which was statistically different from that of pre-operation 4.0(4.0-8.0) (both P<0.001). At 3 months post operation, the improvement rate of 35 patients undergoing STN-DBS was (79.5±26.3)%, which was not statistically different from that of 12 patients undergoing GPi-DBS [(76.9±28.4)%] (P=0.78). The improvement rate of 35 patients receiving STN-DBS was (75.1±27.4)% 6 months after operation, which was not statistically different from that of 12 patients receiving GPi-DBS [(82.8±28.9)%] (P=0.86). Conclusion Deep brain stimulation could effectively relieve PD-related pain. There seems no significant difference between GPi-DBS and STN-DBS in the treatment outcome of PD-related pain. Key words: Parkinson disease; Pain; Deep brain stimulation; Treatment outcome

An overview of pain in Parkinson's disease

Pain is a common non-motor symptom of Parkinson's disease (PD) and the prevalence of pain among PD patients varies because of the disease stage, co-morbidities, and evaluating tools. Risk factors for pain in PD include an early age of onset, long disease duration, motor complications, concomitant depressive symptoms, female gender, and associated medical conditions. In patients with PD, pain can be classified as musculoskeletal pain, chronic body pain (central or visceral), fluctuation-related pain, nocturnal pain, orofacial pain, pain with discolouration/oedema/swelling, and radicular/neuropathic pain; musculoskeletal pain as the most common type. Potential underlying mechanisms include a disruption of peripheral nociception and alterations in central pain threshold/processing. Genetic polymorphisms in genes that confer pain susceptibility might also play a role in the occurrence of pain in PD. In advanced stage of patients with PD, polyneuropathy could occur in patients using high dosage of levodopa. Pain often correlates to other non-motor symptoms of PD, including depression, sleep, and autonomic symptoms. Dopaminergic drugs, non-dopaminergic medications, botulinum toxin, deep brain stimulation, and physiotherapy have shown some benefits for certain types of PD-related pain. An increased awareness of pain as a common non-motor symptom of PD provides further insights into sensory system dysregulation in this disease. In this review, we aim to summarizes the clinical features of pain in patients with PD and emphasize the latest evidence of pain related to levodopa treatment.

Comparison of Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation Surgery on Parkinson Disease–Related Pain

To analyze and compare the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) and globus pallidus internus (GPi)-DBS on Parkinson disease (PD)-related pain. A retrospective study was performed of 64 patients (28 who underwent GPi-DBS and 36 who underwent STN-DBS) with PD-related pain in our hospital between January 2017 and July 2019. A numerical rating scale (NRS) was used to evaluate the degree of pain preoperatively and 4 months after operation, and the unified PD scale III (UPDRS-III) was completed simultaneously to assess motor symptoms. The average NRS score of all 64 patients after surgery was 1.09 ± 1.39, which was significantly lower than that before operation (4.44 ± 1.67; P < 0.0001). The improvement rate of NRS was 75 ± 27% in the 28 GPi-DBS patients and 79 ± 27% in the 36 STN-DBS patients, with no significant difference (P= 0.577). The improvements in NRS and UPDRS-III were significantly correlated in the STN-DBS group (r= 0.3707, P= 0.026) but not significantly correlated in the GPi-DBS group (P= 0.516). Both GPi-DBS and STN-DBS were effective for analyzing PD-related pain and seemed to have similar efficacy. This study provides an important first-step toward determining different DBS targets for controlling PD-related pain. Follow-up prospective research is an appropriate next step on the path to multicenter clinical trials.

Cannabidiol increases the nociceptive threshold in a preclinical model of Parkinson's disease

Medications that improve pain threshold can be useful in the pharmacotherapy of Parkinson's disease (PD). Pain is a prevalent PD's non-motor symptom with a higher prevalence of analgesic drugs prescription for patients. However, specific therapy for PD-related pain are not available. Since the endocannabinoid system is expressed extensively in different levels of pain pathway, drugs designed to target this system have promising therapeutic potential in the modulation of pain. Thus, we examined the effects of the 6-hydroxydopamine- induced PD on nociceptive responses of mice and the influence of cannabidiol (CBD) on 6-hydroxydopamine-induced nociception. Further, we investigated the pathway involved in the analgesic effect of the CBD through the co-administration with a fatty acid amide hydrolase (FAAH) inhibitor, increasing the endogenous anandamide levels, and possible targets from anandamide, i.e., the cannabinoid receptors subtype 1 and 2 (CB1 and CB2) and the transient receptor potential vanilloid type 1 (TRPV1). We report that 6-hydroxydopamine- induced parkinsonism decreases the thermal and mechanical nociceptive threshold, whereas CBD (acute and chronic treatment) reduces this hyperalgesia and allodynia evoked by 6-hydroxydopamine. Moreover, ineffective doses of either FAAH inhibitor or TRPV1 receptor antagonist potentialized the CBD-evoked antinociception while an inverse agonist of the CB1 and CB2 receptor prevented the antinociceptive effect of the CBD. Altogether, these results indicate that CBD can be a useful drug to prevent the parkinsonism-induced nociceptive threshold reduction. They also suggest that CB1 and TRPV1 receptors are important for CBD-induced analgesia and that CBD could produce these analgesic effects increasing endogenous anandamide levels.

Acupuncture Effect and Mechanism for Treating Pain in Patients With Parkinson's Disease.

Non-motor symptoms of Parkinson's disease (PD) have been receiving increasing attention. Approximately half of patients with PD have experience PD-related pain. We investigated the effect and mechanism of acupuncture in patients with PD who have pain. PD patients with pain were divided into acupuncture group and control group. Nine patients completed acupuncture treatment; seven patients who received only an analgesic agent underwent resting-state functional magnetic resonance imaging (rs-fMRI) twice. fMRI was performed to evaluate the functional connectivity of the brain regions. After treatment, a decrease in total scores on the King's Parkinson's Disease Pain Scale (KPPS) and Unified Parkinson's Disease Rating Scale was observed in the acupuncture group (−46.2 and −21.6%, respectively). In the acupuncture group, increased connectivity was observed in four connections, one in the left hemisphere between the middle temporal gyrus (MTG) and precentral gyrus, and three in the right hemisphere between the postcentral gyrus and precentral gyrus, supramarginal gyrus and precentral gyrus, and MTG and insular cortex. A significant correlation was noted between the changes in functional connectivity and KPPS. The involved connection was between the left middle frontal gyrus and the right precentral gyrus (R = −0.698, P = 0.037). Acupuncture could relieve pain in PD patients by modulating brain regions related to both sensory-discriminative and emotional aspects. The present study might increase the confidence of users that acupuncture is an effective and safe analgesic tool that can relieve PD-related pain.

Association of Parkinson’s disease-related pain with plasma interleukin-1, interleukin-6, interleukin-10, and tumour necrosis factor-α

ObjectiveTo study the association between Parkinson's disease (PD)-related pain and plasma interleukin (IL)‑1, IL‑6, IL‑10, and tumour necrosis factor (TNF)‑α levels. MethodsSixty-seven participants were enrolled. Plasma inflammatory cytokine levels of IL-1, IL-6, IL-10, and TNF-α were measured with enzyme-linked immunosorbent assay. We additionally administered the third part of the Unified Parkinson’s Disease Rating Scale (UPDRS III) and Hoehn and Yahr (H–Y) scale stage and recorded the course of the disease, the type and location of the pain, and the use of drugs. ResultsThe level of IL-1 was significantly higher in the PD-with-pain than in the healthy-control group (P < 0.05). There was no significant difference among groups in the other examined cytokine levels. There was a statistically significant difference between the PD-with-pain and the PD-without-pain groups in UPDRS III and H–Y stage. Additionally, the IL-1 level was significantly higher in patients who received a levodopa dosage of >250 mg than in their counterparts who received ≤250 mg, and the IL-1 level was higher in patients with an H–Y stage of >2 and UPDRS III of >27 than in their counterparts with an H–Y stage of ≤2 and UPDRS III of ≤27. The expression of TNF-α was higher in patients aged ≥70 years than in their counterparts aged <70 years. The level of IL-10 was significantly lower in the patients with an H–Y stage of >2 than in their counterparts with an H–Y stage of ≤2. ConclusionThe elevated level of IL-1 and the depressed level of IL-10 in the peripheral blood of patients with PD-related pain suggests that certain inflammatory cytokines may be implicated in the occurrence and clinical symptoms of PD-related pain.

Nonmotor Symptoms and Subthalamic Deep Brain Stimulation in Parkinson's Disease.

Subthalamic deep brain stimulation (STN DBS) is an established treatment for the motor symptoms in patients with advanced Parkinson’s disease (PD). In addition to improvements in motor symptoms, many studies have reported changes in various nonmotor symptoms (NMSs) after STN DBS in patients with PD. Psychiatric symptoms, including depression, apathy, anxiety, and impulsivity, can worsen or improve depending on the electrical stimulation parameters, the locations of the stimulating contacts within the STN, and changes in medications after surgery. Global cognitive function is not affected by STN DBS, and there is no increase in the incidence of dementia after STN DBS compared to that after medical treatment, although clinically insignificant declines in verbal fluency have been consistently reported. Pain, especially PD-related pain, improves with STN DBS. Evidence regarding the effects of STN DBS on autonomic symptoms and sleep-related problems is limited and remains conflicting. Many symptoms of nonmotor fluctuations, which are occasionally more troublesome than motor fluctuations, improve with STN DBS. Although it is clear that NMSs are not target symptoms for STN DBS, NMSs have a strong influence on the quality of life of patients with PD, and clinicians should thus be aware of these NMSs when deciding whether to perform surgery and should pay attention to changes in these symptoms after STN DBS to ensure the optimal care for patients.

Clinical Study on Chronic Pain in Parkinson's Disease Patients in Shanghai, China

Background/Aims: Pain in Parkinson's disease (PD) may be more distressing than that in other nonmotor disabilities. The aims of the present study were to assess the prevalence and identify the epidemiological characteristics of PD-related pain among patients with idiopathic PD in Shanghai, China. Methods: A total of 1,058 patients with definite idiopathic PD were investigated using a structure questionnaire in 12 hospitals in Shanghai. The severity of their motor disorders, antiparkinson treatments, and pain-related observations, such as time points for the onset of pain, duration and degree, body localization, external influences, and treatments for pain, were collected for analysis. Results: Approximately 28% (296 subjects) of all PD patients suffered from PD-related pain. Female patients with pain had a higher age level, were older at PD onset, had a higher frequency of pain, a higher frequency of pain before the onset of PD symptoms, a longer duration of pain, and a higher incidence of pain in the early stage compared to male patients. Larger levodopa-equivalent doses, higher frequencies of sleep disorders and/or motor fluctuation, and/or dyskinesia were found in patients with pain compared to patients without pain. The most frequent pain type was musculoskeletal pain followed by dystonia. The male group had a much shorter pain duration than the female group. The patients experienced more pain before taking antiparkinson drugs compared to after treatment. Conclusion: Chronic PD-related pain is a frequent complaint and complex in PD. The challenge of managing pain in PD patients will hopefully someday result in specific and effective treatment strategies. i 2014 S. Karger AG, Basel

Effects of deep brain stimulation on pain and other nonmotor symptoms in Parkinson disease.

To prospectively evaluate the effect of subthalamic nucleus deep brain stimulation (STN-DBS) on the different characteristics of pain and other nonmotor symptoms (NMS) in patients with Parkinson disease (PD). Forty-four patients with PD and refractory motor symptoms were screened for STN-DBS. Patients were evaluated before and 1 year after surgery. The primary outcome was change in pain prevalence after surgery. Secondary outcome measures were changes in motor function (Unified Parkinson's Disease Rating Scale), characteristics of pain and other NMS using specific scales and questionnaires, and quality of life. Forty-one patients completed the study. The prevalence of pain changed from 70% to 21% after surgery (p < 0.001). There were also significant improvements in pain intensity, NMS, and quality of life after STN-DBS (p < 0.05). Dystonic and musculoskeletal pain responded well to DBS, while central pain and neuropathic pain were not influenced by surgery. There was a strong correlation between the change in pain intensity and the improvement in quality of life (r = 0.708, p < 0.005). No correlation was found between pain improvement and preoperative response to levodopa or motor improvement during stimulation (r = 0.247, p = 0.197 and r = 0.249, p = 0.193, respectively) or with changes in other NMS. STN-DBS decreased pain after surgery, but had different effects in different types of PD-related pain. Motor and nonmotor symptom improvements after STN-DBS did not correlate with pain relief. This study provides Class IV evidence that in patients with idiopathic PD with refractory motor fluctuations, STN-DBS decreases the prevalence of pain and improves quality of life.

Pain in Parkinson's disease associated with COMT gene polymorphisms.

Background. PD patients present high incidence of pain with unknown pathogenesis. Objective. We investigated the relation of COMT polymorphisms rs4633 and rs6267 with PD pain. Subjects and Methods. One hundred PD patients and 105 controls were evaluated with simplified Mc GILL pain scale and VAS scale. PD patients were assessed with H&Y grade, UPDRS score, and HAMD scale. Polymorphisms rs4633 and rs6267 were detected by PCR and direct sequencing. Results. Fifty-seven percent of PD patients experienced pain, consisting of PD-related pain (64.91%) (the majority was dystonia pain) and non-PD-related pain (35.09%) (psychogenic pain was most frequent). The frequency of rs6267 genotype “GT/TT” and allele “T” was higher in PD pain. No difference was observed in frequencies of rs4633 between PD pain and without pain. UPDRS and depression score were higher in PD pain. The onset age was earlier in PD-related pain (57.43 ± 19.71) than non-PD-related pain (63.36 ± 6.88). Conclusion. PD patients possess a high prevalence of pain. Dystonia pain was the most frequent type of PD-related pain. COMT gene rs6267 allele “T” associated with PD pain. PD pain was influenced by disease severity and depression. PD onsets earlier in patients with PD-related pain than non-PD-related pain.

S1-3. Spinal cord stimulation in Parkinson disease

The new devices introduced for spinal cord stimulation (SCS) enable us to choose stimulation contacts and to change the stimulation conditions even after implantation. SCS is used for treating chronic pain that is resistant to medication. Many patients with Parkinson disease (PD) develop pain as a non-motor manifestation. SCS lead to gait improvement in our 5 patients with PD-related pain. The mechanism underlying the SCS-induced improvement in Parkinsonian gait is not known. Gait is thought to be controlled by mainly 3 regions, the midbrain locomotion region, brain stem locomotion region, which is the pedunculopontine nucleus in humans, and spinal central pattern generator (CPG). Dimitrijevic et al. showed locomotion-like reciprocal electromyogram bursts for the lower legs of patients with complete spinal cord injury; this suggests that the CPG is important for gait improvement (Ann N Y Acad Sci. 1998 Nov). Epidural SCS-induced locomotion in mouse and rat models of PD; the induction of locomotion was more pronounced when l-dopa was administered along with SCS, indicating that the central mechanisms play a role in locomotion induction (Fuentes et al., Science 20 March 2009). Further studies are required to elucidate the mechanism of SCS-induced gait improvement in patients with PD.

Cannabis Smoking for Treatment of Parkinson's Disease (PD4.005)

Objective: To assess the clinical effect of cannabis on the motor and non-motor symptoms of PD. Background Recent years have witnessed a substantial increase in the use of cannabis as a therapeutic agent for various medical conditions. The present study was prompted by several reports of the effect of cannabis on motor symptoms in animal models of Parkinson9s disease. Design/Methods: 17 PD patients (mean age 64.2 years, mean disease duration 7.3 years) currently using cannabis as add on therapy were assessed at the Movement Disorders Clinic. The effect of cannabis on the motor symptoms of the disease was evaluated using the Unified Parkinson9s Disease Rating Scale (UPDRS) at baseline and 30 minutes after smoking Cannabis. The effect of cannabis on non-motor symptoms of PD and its side effects were evaluated using the visual analogue scale (VAS), the present pain intensity scale (PPI) ,the Short-Form Mcgill Pain Questionnaire and the Medical Cannabis Survey National Drug and Alcohol Research Center Questionnaire. Results: There was an overall significant improvement in the mean total motor UPDRS score (33.5 ±14.6 before vs. 22.9 ±11.2 after cannabis smoking; P Conclusions: Cannabis holds promise as another treatment option for PD. It can apparently alleviate not only the motor symptoms but also the non-motor symptoms, especially PD-related pain and sleep, thereby improving patient quality of life. Disclosure: Dr. Lotan has nothing to disclose. Dr. Treves has nothing to disclose. Dr. Roditi has nothing to disclose. Dr. Djaldetti has nothing to disclose.