Musculoskeletal Pain in Parkinson's Disease.

BACKGROUND: Musculoskeletal pain is commonly experienced in patients with Parkinson's disease (PD). Few studies have investigated the clinical characteristics and risk factors associated with musculoskeletal pain. OBJECTIVES: To investigate the distribution, clinical characteristics, and factors associated with musculoskeletal pain in a large sample of patients with PD. METHODS: We enrolled 452 patients from two clinics and used a standardized questionnaire to collect demographic and clinical information. Musculoskeletal pain was diagnosed based on the Ford Classification System, and pain severity was assessed with the numeric rating scale (NRS). Multivariate regression models explored the association between clinical features of PD and quality of life and pain. RESULTS: Two hundred and six patients (45.58%) reported musculoskeletal pain, typically in their lower limbs and backs. Levodopa resulted in a ≥30% reduction in pain intensity scores in 170 subjects. Female sex (odds ratio [OR], 1.57; 95% CI, 1.07-2.29) and Levodopa-equivalent daily doses (LEDDs; OR, 3.35; 95% CI, 1.63-6.59) were associated with an increased risk for musculoskeletal pain. Pain duration (p = 0.017), motor symptoms (p < 0.001), and depression (p < 0.001) were significantly associated with quality of life. CONCLUSIONS: The lower limbs and back are common sites of musculoskeletal pain in patients with PD, and up to 82.52% of patients were responsive to Levodopa. Female sex and LEDDs are associated with musculoskeletal pain, suggesting that dopamine deficiencies, and not the motor and non-motor impairment, might be the most critical baseline risk factor of musculoskeletal pain.

Electroacupuncture alleviates inflammatory pain via adenosine suppression and its mediated substance P expression.

BACKGROUND: Acupuncture has been widely used for alleviating pain. However, its mechanisms remain largely enigmatic. OBJECTIVE: In the present study, we focused on whether the analgesic effect of electroacupuncture is related to its regulation on adenosine and substance P expression. METHODS: We established chronic inflammatory pain model in rats through a single injection of Complete Freund's Adjuvant, and then we treated animals using daily electroacupuncture. We applied seven bilateral sessions of electroacupuncture (ST36 and BL60, 0.5 to 1.5 mA, initial strength of 0.5 mA, increased by 0.5 mA every 10 minutes, for 30 minutes per session, one section per day) to Complete Freund's Adjuvant rats for seven days. The analgesic effect of electroacupuncture was evaluated by measuring paw withdrawal threshold in rats that received mechanical and thermal stimulation. RESULTS: Daily electroacupuncture stimulation effectively increased paw withdrawal threshold in Complete Freund's Adjuvant rats. Electroacupuncture increased the adenosine level in zusanli. A further study showed that electroacupuncture could decrease substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1ß, interleukin-6 and CD68 levels in dorsal root ganglion. Interestingly, direct injection of adenosine A1 or substance P receptor antagonists, or dorsal nerve root transection could significantly impair electroacupuncture induced analgesic actions in Complete Freund's Adjuvant rats could and reduce the levels of substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1ß, interleukin-6 and CD68. Finally, we confirmed that direct injection of adenosine A1 receptor agonist replicated the analgesic effect of electroacupuncture. CONCLUSION: Our results indicate regulation of adenosine-mediated substance P secretion. Substance P-mediated pathway may be involved in the analgesia process by electroacupuncture in rats.

High-frequency repetitive transcranial magnetic stimulation over the primary motor cortex relieves musculoskeletal pain in patients with Parkinson's disease: A randomized controlled trial.

BACKGROUND: Pain is common in Parkinson's disease, and there is no effective treatment. We conducted a clinical trial to determine whether high-frequency repetitive transcranial magnetic stimulation over the primary motor cortex alleviates musculoskeletal pain in patients with Parkinson's disease. METHODS: In this single-center and double-blind trial, 52 patients with Parkinson's disease and musculoskeletal pain were randomly allocated to 26-member groups receiving 5 sessions of either 20-Hz repetitive transcranial magnetic stimulation or sham stimulation over the primary motor cortex. The participants underwent assessments in the "ON" medication state at baseline, after the fifth session, and at 2- and 4-week follow-up timepoints. The primary outcomes were pain scores on a numeric rating scale. The secondary outcomes were scores on clinical scales assessing motor symptoms, depression, anxiety, autonomic symptoms, sleep quality, and the overall severity of Parkinson's disease. RESULTS: Analyses revealed significant group × time interactions for numeric rating scale pain scores (p < 0.001), motor symptom scores (p < 0.001), depression scores (p = 0.009), anxiety scores (p = 0.013), and overall disease severity scores (p < 0.001). Post hoc analyses confirmed that the repetitive transcranial magnetic stimulation group, but not the sham stimulation group, exhibited significant improvements in numeric rating scale pain scores, motor symptom scores, depression scores, anxiety scores, and overall disease severity scores. CONCLUSION: High-frequency repetitive transcranial magnetic stimulation over the primary motor cortex may be an effective adjunct therapy for alleviating musculoskeletal pain in patients with Parkinson's disease.

Electroacupuncture alleviates inflammatory pain via adenosine suppression and its mediated substance P expression / A eletroacupuntura alivia a dor inflamatória por meio da supressão de adenosina e da expressão mediada de substância P

ABSTRACT Background: Acupuncture has been widely used for alleviating pain. However, its mechanisms remain largely enigmatic. Objective: In the present study, we focused on whether the analgesic effect of electroacupuncture is related to its regulation on adenosine and substance P expression. Methods: We established chronic inflammatory pain model in rats through a single injection of Complete Freund's Adjuvant, and then we treated animals using daily electroacupuncture. We applied seven bilateral sessions of electroacupuncture (ST36 and BL60, 0.5 to 1.5 mA, initial strength of 0.5 mA, increased by 0.5 mA every 10 minutes, for 30 minutes per session, one section per day) to Complete Freund's Adjuvant rats for seven days. The analgesic effect of electroacupuncture was evaluated by measuring paw withdrawal threshold in rats that received mechanical and thermal stimulation. Results: Daily electroacupuncture stimulation effectively increased paw withdrawal threshold in Complete Freund's Adjuvant rats. Electroacupuncture increased the adenosine level in zusanli. A further study showed that electroacupuncture could decrease substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1β, interleukin-6 and CD68 levels in dorsal root ganglion. Interestingly, direct injection of adenosine A1 or substance P receptor antagonists, or dorsal nerve root transection could significantly impair electroacupuncture induced analgesic actions in Complete Freund's Adjuvant rats could and reduce the levels of substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1β, interleukin-6 and CD68. Finally, we confirmed that direct injection of adenosine A1 receptor agonist replicated the analgesic effect of electroacupuncture. Conclusion: Our results indicate regulation of adenosine-mediated substance P secretion. Substance P-mediated pathway may be involved in the analgesia process by electroacupuncture in rats.

RESUMO Introdução: A acupuntura tem sido amplamente utilizada para alívio de dor. No entanto, seus mecanismos são muito pouco conhecidos. Objetivo: Investigar a relação entre o efeito analgésico da eletroacupuntura e a regulação da expressão de adenosina e de substância P. Métodos: Utilizou-se um modelo de dor inflamatória crônica em ratos por injeção única do Adjuvante Completo de Freund e, em seguida, os animais foram tratados com eletroacupuntura diariamente. Foram aplicadas sete sessões bilaterais de eletroacupuntura (ST36 e BL60, 0,5 a 1,5 mA, força inicial de 0,5 mA, aumentada em 0,5 mA a cada 10 minutos, 30 minutos por sessão, uma sessão por dia) em ratos com Adjuvante Completo de Freund, por sete dias. O efeito analgésico da eletroacupuntura foi avaliado pela medida do limiar de retirada da pata em ratos que receberam estimulações mecânica e térmica. Resultados: A estimulação diária com eletroacupuntura aumentou efetivamente o limiar de retirada da pata em ratos com Adjuvante Completo de Freund. A eletroacupuntura aumentou o nível de adenosina na região zusanli. Estudos posteriores mostraram que a eletroacupuntura poderia diminuir os níveis de substância P, receptor de neurocinina-1, fator de necrose tumoral-alpha, interleucina-1β, interleucina-6 e CD68 nos gânglios da raiz dorsal. Curiosamente, a injeção direta de antagonistas do receptor de adenosina A1 ou de substância P, ou a transecção da raiz do nervo dorsal, podem prejudicar significativamente as ações analgésicas induzidas pela eletroacupuntura em ratos com Adjuvante Completo de Freund e reduzir os níveis de substância P, receptor de neurocinina-1, fator de necrose tumoral-alfa, interleucina-1β, interleucina-6 e CD68. Por fim, confirmamos que a injeção direta de um agonista do receptor da adenosina A1 reproduziu os efeitos analgésicos da eletroacupuntura. Conclusão: Nossos resultados indicam a regulação da secreção da substância P mediada pela adenosina. A via mediada pela substância P pode estar envolvida no processo de analgesia por eletroacupuntura em ratos.