PD-related Pain Research Articles

Posterior insula repetitive transcranial magnetic stimulation for chronic pain in patients with Parkinson disease – pain type matters: A double-blinded randomized sham-controlled trial

ObjectivesAltered somatosensory processing in the posterior insula may play a role in chronic pain development and contribute to Parkinson disease (PD)-related pain. Posterior-superior insula (PSI) repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to have analgesic effects among patients with some chronic pain conditions. This study aimed at assessing the efficacy of PSI-rTMS for treating PD-related pain. MethodsThis was a double-blinded, randomized, sham-controlled, parallel-arm trial (NCT03504748). People with PD (PwP)-related chronic pain underwent five daily PSI-rTMS sessions for a week, followed by once weekly maintenance stimulations for seven weeks. rTMS was delivered at 10 Hz and 80% of the resting motor threshold. The primary outcome was a ≥ 30% pain intensity reduction at 8 weeks compared to baseline. Functionality, mood, cognitive, motor status, and somatosensory thresholds were also assessed. ResultsTwenty-five patients were enrolled. Mean age was 55.2 ± 9.5 years-old, and 56% were female. Nociceptive pain accounted for 60%, and neuropathic and nociplastic for 20% each. No significant difference was found for 30% pain reduction response rates between active (42.7%) and sham groups (14.6%, p = 0.26). Secondary clinical outcomes and sensory thresholds also did not differ significantly. In a post hoc analysis, PwP with nociceptive pain sub-type experienced more pain relief after active (85.7%) compared to sham PSI-rTMS (25%, p = 0.032). ConclusionOur preliminary results suggest that different types of PD-related pain may respond differently to treatment, and therefore people with PD may benefit from having PD-related pain well characterized in research trials and in clinical practice.

Self-management of primary dysmenorrhea-related pain: cross-sectional study on non-pharmacological interventions.

Aim: Different nonpharmacological strategies are adopted to decrease primary dysmenorrhea (PD)-related pain. The present study aimed to verify women's use of nonpharmacological methods for pain and compare them with evidence from the literature.Materials & methods: A two-step study was conducted, comprising an online survey with 9144 women to assess nonpharmacological strategies for relieving PD-related pain, and a literature review on PubMed of verify the evidence of nonpharmacological methods.Results: Many women reported using heat therapy (61.5%), tea (42.4%) and massage (30.9%) to alleviate menstrual pain. However, the literature on these methods is limited.Conclusion: Several nonpharmacological methods are used by women to relieve PD-related pain and studies with low bias risk are needed to prove their effectiveness.

TDCS for parkinson‘s disease disease-related pain: A randomized trial

ObjectiveTo evaluate the effects of transcranial direct current stimulation (tDCS) on Parkinson’s disease (PD)-related pain. MethodsThis triple-blind randomized controlled trial included twenty-two patients (age range 38–85, 10 male) with PD-related pain. Eleven subjects received ten sessions of 20 minutes tDCS over the primary motor cortex contralateral to pain at 2 mA intensity. Eleven subjects received sham stimulation. Outcome measures included changes in the Kinǵs Parkinsońs Pain Scale (KPPS), Brief Pain Inventory (BPI), widespread mechanical hyperalgesia (WMH), temporal summation of pain (TS), and conditioned pain modulation (CPM). ResultsSignificant differences were found in KPPS between groups favoring the active-tDCS group compared to the sham-tDCS group at 15-days follow-up (p = 0.014) but not at 2 days post-intervention (p = 0.059). The active-group showed significant improvements over the sham-group after 15 days (p = 0.017). Significant changes were found in CPM between groups in favor of active-tDCS group at 2 days post-intervention (p = 0.002) and at 15 days (p = 0.017). No meaningful differences were observed in BPI or TS. ConclusionstDCS of the primary motor cortex alleviates perceived PD-related pain, reduces pain sensitization, and enhances descending pain inhibition. SignificanceThis is the first study to test and demonstrate the use of tDCS for improving PD-related pain.

Translation and cross-cultural adaptation of the Spanish version of the King’s Parkinson’s Disease Pain Scale (KPPS)

Purpose To translate and cross-culturally adapt the King’s Parkinson’s Disease Pain Scale (KPPS) into Spanish. Methods The English KPPS was forward translated into Spanish, back translated, and revised by the original developers. Cross-cultural adaptation of relevant target groups was conducted following COSMIN standards. Cognitive pretesting in Spanish people with Parkinson’s Disease (PD) and pain was performed via three semi-structured focus group meetings. Changes were implemented based on qualitative and quantitative analyses. A Delphi study (two rounds) of individual assessments by Spanish experts was conducted. Changes were implemented based on the Content Validity Index (CVI) at item and scale levels (I-CVI/S-CVI). Results Five Spanish professionals performed the initial translation. Thirty-eight inter-translation inconsistencies were identified, and consensus was reached for a unified version. After back translation and confirmation with scale developers, the pre-final Spanish KPPS was obtained. Cognitive pretesting in 30 people with PD-related pain identified 5 items where terminology changes were made to assure comprehensibility. The Delphi study in 14 Spanish experts underlined the necessity to further modify two items. After the second round, all experts agreed on the modifications and I-CVI and S-CVI were satisfactory. Conclusions The KPPS was successfully translated and cross-culturally adapted into Spanish.

Prevalence, pain intensity and symptoms associated with primary dysmenorrhea: a cross-sectional study

BackgroundPrimary dysmenorrhea (PD) is an etiological cyclic pelvic pain related to the menstrual period; it can negatively impact women’s quality of life and productivity. The aim of the present study was to estimate the prevalence of PD and analyze associated symptoms in Brazilian women.MethodsAn online cross-sectional study was carried out in Brazil, with a structured questionnaire regarding dysmenorrhea and associated symptoms. PD intensity was measured with the Numerical Rating Scale for Pain and classified as mild (1–3), moderate (4–7) and severe (> 8). The association between qualitative variables was performed using Pearson’s Chi-Square Test. The quantification of this association was measured using multinomial logistic regression models, with calculation of Odds Ratio and confidence interval. A significance level of 5% was considered.ResultsA total of 10,070 women were included. Most participants classified PD intensity as moderate (40.4%, 41.9% and 49.7%) and severe (21.2%, 24.8% and 28.4%) in the previous month, 3 months and 5 years, respectively. The most common symptoms associated with PD were irritability, abdominal distension sensation, anxiety and feeling more emotional. The increased of the risk (OR > 1.0) for moderate and severe PD-related pain intensity is related to age, nulliparity and presence PD since adolescence.ConclusionThere is a high prevalence of PD among Brazilian women, and the most common symptoms reported were irritability, abdominal distension sensation, anxiety and feeling more emotional.

Pain in Parkinson disease: a deep phenotyping study.

In our prospective cross-sectional study, we comprehensively characterized Parkinson disease (PD)-related pain in monocentrically recruited patients with PD using standardized tools of pain assessment and categorization. One hundred fifty patients were systematically interviewed and filled in questionnaires for pain, depression, motor, and nonmotor symptoms. Patients with PD-related pain (PD pain), patients without PD-related pain (no PD pain), and patients without pain (no pain) were compared. Pain was present in 108/150 (72%) patients with PD, and 90/150 (60%) patients were classified as having PD-related pain. Most of the patients with PD (67/90, 74%) reported nociceptive pain, which was episodic (64/90, 71%), primarily nocturnal (56/90, 62%), and manifested as cramps (32/90, 36%). Parkinson disease-related pain was most frequently located in the feet (51/90, 57%), mainly at the toe joints (22/51, 43%). 38/90 (42%) patients with PD-related pain received analgesic medication with nonsteroidal anti-inflammatory drugs being the most frequently used (31/42, 82%) and opioids most effective (70% pain reduction of individual maximum pain intensities, range 22%-100%, confidence interval 50%-90%). All patients received oral PD treatment; however, levodopa equivalent dose showed no correlation with mean pain intensities (Spearman ρ = 0.027, P > 0.05). Our data provide a comprehensive analysis of PD-related pain, giving evidence for mainly non-neuropathic podalgia, which bears the potential to rethink assessment and analgesic treatment of pain in PD in clinical practice.

Pain characterization in patients with Parkinson's disease.

Patients with Parkinson's disease (PD) often report chronic pain, which is one of the most complex non-motor symptoms. Therefore, this study aims to review the literature on the characteristics of pain in patients with PD. A systematic literature review was conducted following MOOSE recommendations. Observational studies reporting pain in patients with PD were included. No time restrictions were applied, but studies in Portuguese, Spanish, and English were considered. The search was performed in PubMed®, LILACS, and SciELO databases. Twenty-six articles of observational studies were identified, reporting an average pain prevalence of 67.36%, emphasizing the significance of this symptom in the PD population. Pain was reported in various body regions, including lower limbs, upper limbs, lumbar spine, cervical spine, and other joints. Pain classification varied, encompassing musculoskeletal pain, PD-related pain, neuropathic pain, and dystonic pain, among others. Pain in patients with PD is a prevalent and multifactorial condition, significantly impacting patients' quality of life. Heterogeneity in data across included studies was observed, highlighting the need for additional research to elucidate the underlying mechanisms of pain in patients with PD and develop effective therapeutic strategies to address this symptom and improve the quality of life for individuals living with the disease.

Complications of Peritoneal Dialysis Part I: Mechanical Complications.

Peritoneal dialysis (PD) is a form of KRT that offers flexibility and autonomy to patients with ESKD. It is associated with lower costs compared with hemodialysis in many countries. However, it can be associated with unexpected interruptions to or discontinuation of therapy. Timely diagnosis and resolution are required to minimize preventable modality change to hemodialysis. This review covers mechanical complications, including leaks, PD hydrothorax, hernias, dialysate flow problems, PD-related pain, and changes in respiratory mechanics. Most mechanical complications occur early, either as a result of PD catheter insertion or the introduction of dialysate and consequent increased intra-abdominal pressure. Late mechanical complications can also occur and may require different treatment.

Parkinson's Disease-related Pains are Not Equal: Clinical, Somatosensory and Cortical Excitability Findings in Individuals With Nociceptive Pain

Chronic pain is a frequent and burdensome nonmotor symptom of Parkinson's disease (PD). PD-related chronic pain can be classified as nociceptive, neuropathic, or nociplastic, the former being the most frequent subtype. However, differences in neurophysiologic profiles between these pain subtypes, and their potential prognostic and therapeutic implications have not been explored yet. This is a cross-sectional study on patients with PD (PwP)-related chronic pain (ie, started with or was aggravated by PD). Subjects were assessed for clinical and pain characteristics through questionnaires and underwent quantitative sensory tests and motor corticospinal excitability (CE) evaluations. Data were then compared between individuals with nociceptive and non-nociceptive (ie, neuropathic or nociplastic) pains. Thirty-five patients were included (51.4% male, 55.7 ± 11.0 years old), 20 of which had nociceptive pain. Patients with nociceptive PD-related pain had lower warm detection threshold (WDT, 33.34 ± 1.39 vs 34.34 ± 1.72, P = .019) and mechanical detection threshold (MDT, 2.55 ± 1.54 vs 3.86 ± .97, P = .007) compared to those with non-nociceptive pains. They also presented a higher proportion of low rest motor threshold values than the non-nociceptive pain ones (64.7% vs 26.6%, P = .048). In non-nociceptive pain patients, there was a negative correlation between WDT and non-motor symptoms scores (r = −.612, P = .045) and a positive correlation between MDT and average pain intensity (r = .629, P = .038), along with neuropathic pain symptom scores (r = .604, P = .049). It is possible to conclude that PD-related chronic pain subtypes have distinctive somatosensory and CE profiles. These preliminary data may help better frame previous contradictory findings in PwP and may have implications for future trial designs aiming at developing individually-tailored therapies. PerspectiveThis work showed that PwP-related nociceptive chronic pain may have distinctive somatosensory and CE profiles than those with non-nociceptive pain subtypes. These data may help shed light on previous contradictory findings in PwP and guide future trials aiming at developing individually-tailored management strategies.

Analgesic effect of safinamide mesylate in a rat model of neuropathic pain

Pain is one of the most frequent non-motor symptoms of Parkinson’s disease (PD). Neuropathic pain is highly prevalent in PD and negatively affects the quality of life of patients with PD. However, there is currently no evidence-based treatment for its control. Safinamide, a monoamine oxidase (MAO)-B inhibitor with a sodium channel inhibitory effect, showed improvement in PD-related pain in several clinical trials. However, it is unclear for which of the various types of pain in PD safinamide is effective. The aim of the present study was to examine the effect of safinamide on neuropathic pain in a rat model of chronic constriction injury (CCI). Pain was evaluated on postoperative days 14 and 21 using von Frey or weight-bearing tests. Male CCI model rats showed a decreased paw withdrawal threshold and a weight-bearing deficit on postoperative days 14 and 21. Single oral administration of safinamide (15, 30, 45 or 70 mg/kg) dose-dependently improved neuropathic pain in both pain assessments on day 14. Subsequently, the 15 and 45 mg/kg dose groups were administered safinamide orally once daily until day 21. With repeated administration, the effect of safinamide on pain was enhanced. The present findings show that safinamide improves neuropathic pain in male CCI model rats. Further animal model research and pathological and molecular pharmacological investigations are warranted.

Pain in Parkinson disease: mechanistic substrates, main classification systems, and how to make sense out of them.

Parkinson disease (PD) affects up to 2% of the general population older than 65 years and is a major cause of functional loss. Chronic pain is a common nonmotor symptom that affects up to 80% of patients with (Pw) PD both in prodromal phases and during the subsequent stages of the disease, negatively affecting patient's quality of life and function. Pain in PwPD is rather heterogeneous and may occur because of different mechanisms. Targeting motor symptoms by dopamine replacement or with neuromodulatory approaches may only partially control PD-related pain. Pain in general has been classified in PwPD according to the motor signs, pain dimensions, or pain subtypes. Recently, a new classification framework focusing on chronic pain was introduced to group different types of PD pains according to mechanistic descriptors: nociceptive, neuropathic, or neither nociceptive nor neuropathic. This is also in line with the International Classification of Disease-11, which acknowledges the possibility of chronic secondary musculoskeletal or nociceptive pain due to disease of the CNS. In this narrative review and opinion article, a group of basic and clinical scientists revise the mechanism of pain in PD and the challenges faced when classifying it as a stepping stone to discuss an integrative view of the current classification approaches and how clinical practice can be influenced by them. Knowledge gaps to be tackled by coming classification and therapeutic efforts are presented, as well as a potential framework to address them in a patient-oriented manner.

Periaqueductal grey and spinal cord pathology contribute to pain in Parkinson’s disease

Pain is a key non-motor feature of Parkinson’s disease (PD) that significantly impacts on life quality. The mechanisms underlying chronic pain in PD are poorly understood, hence the lack of effective treatments. Using the 6-hydroxydopamine (6-OHDA) lesioned rat model of PD, we identified reductions in dopaminergic neurons in the periaqueductal grey (PAG) and Met-enkephalin in the dorsal horn of the spinal cord that were validated in human PD tissue samples. Pharmacological activation of D1-like receptors in the PAG, identified as the DRD5+ phenotype located on glutamatergic neurons, alleviated the mechanical hypersensitivity seen in the Parkinsonian model. Downstream activity in serotonergic neurons in the Raphé magnus (RMg) was also reduced in 6-OHDA lesioned rats, as detected by diminished c-FOS positivity. Furthermore, we identified increased pre-aggregate α-synuclein, coupled with elevated activated microglia in the dorsal horn of the spinal cord in those people that experienced PD-related pain in life. Our findings have outlined pathological pathways involved in the manifestation of pain in PD that may present targets for improved analgesia in people with PD.

Efectiveness of transcranial Direct Current Stimulation (tDCS) on Parkinson´s Disease (PD)-related pain: effects on pain processing features in PD patients

Abstract Background: PD-related pain is a prevalent and under-reported non-motor symptom that severely impacts patients' quality of life. Nevertheless, there is a lack of non-pharmacologic protocols to manage this symptom. Regarding their pain processing features, PD patients have reduced pain thresholds (PT), an augmented Temporal Summation (TS) after repetitive nociceptive stimulus, and the impairment of their Conditioned Pain Modulation (CPM) is correlated with greater severity and premature onset of the disease. Both pain and PD cause a reduction in corticomotor excitability, governed by the primary motor cortex (M1). TDCS applied to M1 increases corticospinal excitability, not only in the stimulated area but also in sensory and emotional pain processing structures. TDCS would be effective in treating central sensitivity-related pain, however, it has not been tested yet in PD-related pain. Objective: To estimate the effectiveness of tDCS on pain processing features in PD patients. Methods: This is a randomized, triple-blind, parallel design clinical trial with 18 subjects (61.3±11.52 years old). They were randomly assigned to one of two intervention groups: active-tDCS (9) vs. sham-tDCS (9). The active group received 10 consecutive sessions of 20 min of tDCS with active anode on M1 at 2 mA intensity. The sham group followed the same protocol, but the tDCS stimulator was turned off at 30 seconds. All subjects were evaluated pre, post, and 15 days post-intervention with the variables Pain Expansion (the sum of PTs), TS, and CPM. Results: There are statistically significant improvements between groups post-intervention for CPM (p=0.010), and 15 days post-intervention for CPM (p=0.032) and Pain Expansion (p=0.022) in favor of active-tDCS when compared with sham-tDCS. There are no statistically significant differences in the group-time interaction for the TS (p= 0.780). Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: tDCS, Parkinson´s Disease, Pain Expansion, Conditioned Pain Modulation

VEGF-Expressing Mesenchymal Stem Cell Therapy for Safe and Effective Treatment of Pain in Parkinson’s Disease

Vascular endothelial growth factor (VEGF) is a pro-angiogenic factor that mediates the differentiation and function of vascular endothelial cells. VEGF has been implicated in modulating various pains. However, the effects of VEGF in Parkinson’s disease (PD)-related pain have not been studied. The goal of this study was to understand the effects of VEGF-expressing mesenchymal stem cells (MSCs) on PD-related pain and the involved mechanisms. We used two types of MSCs: hAMSC-Vector-GFP and hAMSC-VEGF189-GFP in PD mice. Then, the expression of VEGF and the viability have been compared between two types of MSCs. To demonstrate the therapeutic effect of hAMSC-VEGF189-GFP, we transplanted each cell line in a PD mouse model. Head mechanical withdrawal thresholds were examined. hAMSC-VEGF189-GFP was associated with significantly increased VEGF expression and slightly increased viability, compared with hAMSC-Vector-GFP. The transplanted hAMSC-VEGF189-GFP significantly improved mechanical allodynia and inhibited transient receptor potential vanilloid 1 (TRPV1) expression in site. And such pain relief effects could be partially blocked by TRPV1 agonist. However, we did not observe tumor generation or neuron degeneration in hAMSC-VEGF189-GFP-transplanted animals. Taken together, our data suggest that hAMSC-VEGF189-GFP is safely therapeutically appropriate for treating PD-related pain. VEGF inhibits TRPV1 expression, which may contribute to its analgesic properties.

Chronic Pain And Levodopa Therapy in Parkinson’s Disease Patients

Background: Pain is a frequent non-motor symptom in patients with Parkinson’s disease (PD) and appears to be related to low levels of dopamine. This study describes the characteristics of chronic pain in a group of PD patients undergoing levodopa therapy. Methods: This was a cross-sectional study. The pain was assessed in 21 selected PD patients with chronic pain using several scales and instruments. Changes in pain response from levodopa use (wearing-off phenomenon) were monitored. Results: The most prevalent type of pain was nociceptive (71.4%), musculoskeletal and dystonic, but neuropathic pain accounted for the highest pain score according to the Parkinson’s Disease Pain Classification System (45.5±30.08). Patients with neuropathic, nociplastic, or nociceptive pain upon wearing-off were those who responded to levodopa (p=0.999). According to the McGill questionnaire, patients with pain upon wearing-off had higher scores in the affective/motivational dimension (p=0.022). Conclusion: Using a new pain classification and scoring tool, this study corroborates a good response to levodopa in PD-related pain.

Idiopathic Parkinson's disease and chronic pain in the era of deep brain stimulation: a systematic review and meta-analysis.

Pain is the most common nonmotor symptom of Parkinson's disease (PD) and is often undertreated. Deep brain stimulation (DBS) effectively mitigates the motor symptoms of this multisystem neurodegenerative disease; however, its therapeutic effect on nonmotor symptoms, especially pain, remains inconclusive. While there is a critical need to help this large PD patient population, guidelines for managing this significant disease burden are absent. Herein, the authors systematically reviewed the literature and conducted a meta-analysis to study the influence of traditional (subthalamic nucleus [STN] and globus pallidus internus [GPi]) DBS on chronic pain in patients with PD. The authors performed a systematic review of the literature and a meta-analysis following PRISMA guidelines. Risk of bias was assessed using the levels of evidence established by the Oxford Centre for Evidence-Based Medicine. Inclusion criteria were articles written in English, published in a peer-reviewed scholarly journal, and about studies conducting an intervention for PD-related pain in no fewer than 5 subjects. Twenty-six studies were identified and included in this meta-analysis. Significant interstudy heterogeneity was detected (Cochran's Q test p < 0.05), supporting the use of the random-effects model. The random-effects model estimated the effect size of DBS for the treatment of idiopathic pain as 1.31 (95% CI 0.84-1.79). The DBS-on intervention improved pain scores by 40% as compared to the control state (preoperative baseline or DBS off). The results indicated that traditional STN and GPi DBS can have a favorable impact on pain control and improve pain scores by 40% from baseline in PD patients experiencing chronic pain. Further trials are needed to identify the subtype of PD patients whose pain benefits from DBS and to identify the mechanisms by which DBS improves pain in PD patients.

Inhibition of Spinal 5-HT3 Receptor and Spinal Dorsal Horn Neuronal Excitability Alleviates Hyperalgesia in a Rat Model of Parkinson's Disease.

Pain in Parkinson's disease (PD) is increasingly recognized as a major factor associated with poor life quality of PD patients. However, classic therapeutic drugs supplying dopamine have limited therapeutic effects on PD-related pain. This suggests that there is a mechanism outside the dopamine system that causes pain in PD. Our previous study demonstrated that 6-OHDA induced PD model manifested hyperalgesia to thermal and mechanical stimuli and decreased serotonin (5-hydroxytryptamine; 5-HT) in the spinal dorsal horn (SDH). Several 5-HT receptor subtypes have been confirmed to be associated with nociception in the spinal cord, such as 5-HT1A receptor, 5-HT1B receptor, 5-HT2 receptor, 5-HT3 receptor, and 5-HT7 receptor. Most research has shown that 5-HT1A receptor and 5-HT3 receptor play a key role in pain transmission in the spinal cord. We hypothesized that hyperalgesia of 6-OHDA rats may be related to increased excitability of SDH neurons, and functional change of 5-HT3 receptor may reverse the hyperalgesia of 6-OHDA lesioned rats and decrease cell excitability of SDH neurons. To test this hypothesis, we used whole-cell patch-clamp and pharmacological methods to evaluate the effect of 5-HT3 receptor and 5-HT1A receptor on the hyperalgesia of 6-OHDA rats. The results suggested that increased excitability in SDH neurons could be reversed by 5-HT3 receptor antagonist ondansetron (20μmol/L) and palosetron (10μmol/L), but not 5-HT3 receptor agonist m-CPBG (30μmol/L) and SR 57,727 (10μmol/L), 5-HT1A receptor agonist 8-OH DPAT (10μmol/L) and eptapirone (10μmol/L) and 5-HT1A receptor antagonist WAY-100635 (10μmol/L) and p-MPPI (10μmol/L). Intrathecal injection of ondansetron (0.1mg/kg) but not m-CPBG (0.1mg/kg), 8-OH DPAT (0.1mg/kg), and WAY-100635 (0.1mg/kg) significantly attenuated the mechanical hyperalgesia and thermal hyperalgesia in 6-OHDA lesioned rats. In conclusion, the present study suggests that inhibition of spinal 5-HT3 receptor and SDH neuronal excitability alleviates hyperalgesia in PD rats. Our study provides a novel mechanism or therapeutic strategy for pain in patients with PD.

Collective Expert Perspectives on the Use of Safinamide as Adjunctive Therapy for Parkinson's Disease: Online-Based Delphi Survey.

Background Safinamide is a selective, reversible monoamine oxidase-B inhibitor with a sodium channel inhibitory effect. Published clinical evidence supports safinamide as an effective therapy for Parkinson's disease (PD) with wearing-off. However, to date, no consensus recommendations have been available to guide physicians in Asia on the optimal use of safinamide in clinical practice. To summarize opinions on the optimal patient profile and methods of using safinamide in common clinical scenarios, Japanese movement disorder specialists with expertise in PD investigated the perspectives of neurologists and neurosurgeons. Methods The Delphi panel approach was used to summarize the opinions of panelists. The panel comprised doctors from Japan with extensive clinical practice experience in the use of safinamide (n = 46 at the final round). The consensus was defined as 80% or more agreement between panelists for each scenario at the final round. Results There was a high level of agreement that patients with the following symptoms are suitable for safinamide treatment such as bradykinesia (100%), rigidity (95.7%), and/or gait disorder (89.1%) based on motor symptoms and PD-related pain (97.8%) and/or depression or apathy (93.5%) based on non-motor symptoms. Morning-off (95.7%), but not dyskinesia (71.7%), also reached consensus. The use of high-dose safinamide (100 mg/day) was recommended when the improvement in PD symptoms is insufficient and increasing the doses of other anti-PD medications is difficult (97.8%) or when the abovementioned non-motor symptoms adversely affect daily life (93.5%). Conclusions This report provides expert perspectives on the use of safinamide for a wide range of clinical scenarios in Japan.

Gender Differences in Pain Subtypes among Patients with Parkinson's Disease.

To determine the influence of gender on the different pain subtypes experienced by patients with Parkinson's disease (PD). Two hundred patients with PD were recruited for this research. Demographic features for all patients were recorded, as well as clinical data on age, disease duration, levodopa equivalent daily dose (LEDD), and scores for Unified Parkinson's Disease Rating Scale-III (UPDRS III), Hoehn-Yahr Scale (H&Y), King's Parkinson's disease Pain Scale (KPPS), Pittsburgh Sleep Quality Index (PSQI), Mini-mental State Examination (MMSE), activities of daily living scale (ADL), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA) scales. Male and female patients showed no significant differences in terms of age, disease duration, LEDD, H&Y stage, and UPDRS III, HAMD, HAMA, PSQI and ADL scores. Women showed significantly lower MMSE than men, but their KPPS scores were higher (both p < 0.05). Female also showed significantly higher scores for chronic, fluctuation-related pain and oro-facial pain and more discoloration;edema/swelling than males (p < 0.05). Female gender was associated with pain in PD patients, with stronger associations for certain subtypes of PD-related pain.

Association between sleep disturbances and pain subtypes in Parkinson's disease.

To explore the influence of sleep disturbances on the various pain subtypes experienced by patients with Parkinson's disease (PD). A cohort of eighty-eight patients with PD-related pain 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), Pittsburgh Sleep Quality Index (PSQI), King's Parkinson's disease Pain Scale (KPPS), visual analog scale (VAS), Mini-Mental State Examination (MMSE), activities of daily living scale (ADL), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA), were recorded. The prevalence of sleep disorders was 76.1% in patients with PD-related pain. Among these patients, the group of poor sleep had more severe motor symptoms, more anxiety and depression symptoms, lower functional independence, and experienced more pain, such as musculoskeletal pain, chronic pain, fluctuation related pain, nocturnal pain, and discoloration/edema/swelling (p < 0.05). In addition, PSQI scores correlated positively with the scores of all 7 domains in KPPS (p < 0.05). H&Y stage and PSQI were significant independent variables explaining 50.0% of the variance in KPPS scores. Sleep disturbance showed an association with pain in PD patients and may have a greater effect on some certain subtypes of PD-related pain than others.