Prevalence, Classification, and Etiology of Pain in Parkinson's Disease: Association between Parkinson's Disease and Fibromyalgia or Chronic Widespread Pain

Toda, Katsuhiro; Harada, Taishi

doi:10.1620/tjem.222.1

Cited by 27 publications

(21 citation statements)

References 31 publications

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“…In summary, although traditional STN HFS has proven efficacy in treating the motor symptoms of PD, 4 patients can develop new pain symptoms or continue to have chronic pain. 56 Given the changes in sensory detection and pain thresholds in our patient cohort, we suggest that STN LFS may be a future option to consider in the treatment of PD-related pain refractory to other therapies. Further studies should address whether long-term STN LFS improves chronic pain status in these patients.…”

Section: Discussionmentioning

confidence: 81%

Effect of low-frequency deep brain stimulation on sensory thresholds in Parkinson's disease

Belasen¹,

Rizvi²,

Gee

et al. 2017

JNS

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OBJECTIVE Chronic pain is a major distressing symptom of Parkinson's disease (PD) that is often undertreated. Subthalamic nucleus (STN) deep brain stimulation (DBS) delivers high-frequency stimulation (HFS) to patients with PD and has been effective in pain relief in a subset of these patients. However, up to 74% of patients develop new pain concerns while receiving STN DBS. Here the authors explore whether altering the frequency of STN DBS changes pain perception as measured through quantitative sensory testing (QST). METHODS Using QST, the authors measured thermal and mechanical detection and pain thresholds in 19 patients undergoing DBS via HFS, low-frequency stimulation (LFS), and off conditions in a randomized order. Testing was performed in the region of the body with the most pain and in the lower back in patients without chronic pain. RESULTS In the patients with chronic pain, LFS significantly reduced heat detection thresholds as compared with thresholds following HFS (p = 0.029) and in the off state (p = 0.010). Moreover, LFS resulted in increased detection thresholds for mechanical pressure (p = 0.020) and vibration (p = 0.040) compared with these thresholds following HFS. Neither LFS nor HFS led to changes in other mechanical thresholds. In patients without chronic pain, LFS significantly increased mechanical pain thresholds in response to the 40-g pinprick compared with thresholds following HFS (p = 0.032). CONCLUSIONS Recent literature has suggested that STN LFS can be useful in treating nonmotor symptoms of PD. Here the authors demonstrated that LFS modulates thermal and mechanical detection to a greater extent than HFS. Low-frequency stimulation is an innovative means of modulating chronic pain in PD patients receiving STN DBS. The authors suggest that STN LFS may be a future option to consider when treating Parkinson's patients in whom pain remains the predominant complaint.

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Section: Discussionmentioning

confidence: 81%

Effect of low-frequency deep brain stimulation on sensory thresholds in Parkinson's disease

Belasen¹,

Rizvi²,

Gee

et al. 2017

JNS

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“…20 The wide variability in prevalence is due, in part, to lack of (1) visibility to the physician, (2) reporting by the patient, (3) treatment priority if reported, and (4) attention to sufficient objective signs that are disregarded. 21 Distribution of pain types in PD includes musculoskeletal pain (48%), dystonic pain (26%), neuropathic pain (13%), and non-localized/central pain (8%). 20, 22 Musculoskeletal pain originates from rigidity or skeletal deformity due to Parkinsonism.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the safety and immunomodulatory effects of sargramostim in a randomized, double-blind phase 1 clinical Parkinson’s disease trial

Gendelman

Zhang

Santamaria

et al. 2017

npj Parkinson's Disease

110

118

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A potential therapeutic role for immune transformation in Parkinson’s disease evolves from more than a decade of animal investigations demonstrating regulatory T cell (Treg) nigrostriatal neuroprotection. To bridge these results to human disease, we conducted a randomized, placebo-controlled double-blind phase 1 trial with a well-studied immune modulator, sargramostim (granulocyte-macrophage colony-stimulating factor). We enrolled 17 age-matched non-Parkinsonian subjects as non-treated controls and 20 Parkinson’s disease patients. Both Parkinson’s disease patients and controls were monitored for 2 months for baseline profiling. Parkinson’s disease patients were then randomized into two equal groups to self-administer placebo (saline) or sargramostim subcutaneously at 6 μg/kg/day for 56 days. Adverse events for the sargramostim and placebo groups were 100% (10/10) and 80% (8/10), respectively. These included injection site reactions, increased total white cell counts, and upper extremity bone pain. One urticarial and one vasculitis reaction were found to be drug and benzyl alcohol related, respectively. An additional patient with a history of cerebrovascular disease suffered a stroke on study. Unified Parkinson’s disease rating scale, Part III scores in the sargramostim group showed modest improvement after 6 and 8 weeks of treatment when compared with placebo. This paralleled improved magnetoencephalography-recorded cortical motor activities and Treg numbers and function compared with pretreated Parkinson’s disease patients and non-Parkinsonian controls. Peripheral Treg transformation was linked to serum tryptophan metabolites, including L-kynurenine, quinolinic acid, and serotonin. These data offer a potential paradigm shift in modulating immune responses for potential therapeutic gain for Parkinson’s disease. Confirmation of these early study results requires larger numbers of enrolled patients and further clinical investigation.

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“…In conclusion, although HFS STN DBS is a well validated approach to managing motor symptoms in patients with PD (Benabid et al ., ), these individuals often present with debilitating chronic pain (Toda & Harada, ). Our data suggests that both HFS and LFS improves mechanical and thermal thresholds in 6OHDA‐lesioned rats, and it may be pragmatic to consider using LFS when treating PD patients where pain remains a predominant complaint and motor symptoms can still be controlled.…”

Section: Discussionmentioning

confidence: 99%

The effects of subthalamic deep brain stimulation on mechanical and thermal thresholds in 6OHDA‐lesioned rats

Gee

Chen

Ramirez‐Zamora

et al. 2015

Eur J of Neuroscience

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Chronic pain is a major complaint for up to 85% of Parkinson Disease patients, however, often not identified as a symptom of Parkinson’s disease. Adequate treatment of motor symptoms often provides analgesic effects in Parkinson’s patients, how this occurs remains unclear. Studies have shown both Parkinson’s patients and 6-hydroxydopamine lesioned rats exhibit decreased sensory thresholds. In humans, some show improvements in these deficits after subthalamic deep brain stimulation, while others report no change. Differing methods of testing and response criteria may explain these varying results. We examined this effect in 6-hydroxydopamine lesioned rats. Sprague dawley rats were unilaterally implanted with subthalamic stimulating electrodes in the lesioned right hemisphere and sensory thresholds were tested using vonFrey, tail flick and hot plate tests. Tests were done during and off subthalamic stimulation at 50 and 150Hz to assess its effects on sensory thresholds. 6-hydroxydopamine lesioned animals exhibited lower mechanical (left paw, p<0.01) and thermal thresholds than shams (hot plate, p<0.05). Both 50 and 150Hz increased mechanical (left paw; p<0.01) and thermal thresholds in 6-hydroxydopamine lesioned rats (HPT; 150Hz, p<0.05, 50Hz, p<0.01). Interestingly, the magnitude of improvement in mechanical thresholds during LFS was similar between animals, whereas during HFS was much more diverse. This study shows that subthalamic deep brain stimulation improves mechanical allodynia and thermal hyperalgesia in 6-hydroxydopamine lesioned animals at both high and low frequencies. Furthermore, we suggest considering using low frequency stimulation when treating Parkinson’s patients where pain remains the predominant complaint.

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Prevalence, Classification, and Etiology of Pain in Parkinson's Disease: Association between Parkinson's Disease and Fibromyalgia or Chronic Widespread Pain

Cited by 27 publications

References 31 publications

Effect of low-frequency deep brain stimulation on sensory thresholds in Parkinson's disease

Effect of low-frequency deep brain stimulation on sensory thresholds in Parkinson's disease

Evaluation of the safety and immunomodulatory effects of sargramostim in a randomized, double-blind phase 1 clinical Parkinson’s disease trial

The effects of subthalamic deep brain stimulation on mechanical and thermal thresholds in 6OHDA‐lesioned rats

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