Long-Term Pain Outcomes With DBS in Parkinson's

Pauline Anderson

April 10, 2015

The beneficial effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on pain in patients with Parkinson's disease (PD) persist long term, a new study has found.

The study showed that all off-state (not taking medication) pain experienced by patients before the operation improved or disappeared 8 years later.

However, new pain, mostly musculoskeletal pain, developed in 75% of patients during the follow-up period.

Musculoskeletal pain needs to be addressed independently, according to the study authors, led by Yu Jin Jung, MD, Department of Neurology, College of Medicine, Kyung Hee University, Seoul, Korea.

"The results of the present study highlight once again that musculoskeletal problems should be considered when predicting the operative outcome before surgery, and continuous evaluation and treatment of musculoskeletal pain should be performed after surgery," they conclude.

The study was published online March 23 in JAMA Neurology.

Parkinson's and Pain

The prevalence of pain is reported to be 40% to 85% among patients with PD. PD-related pain likely involves dysfunction of both dopaminergic and nondopaminergic basal ganglia pathways, which may explain why some pain types are responsive to levodopa while others aren't, the authors note.

The current analysis included 24 patients with PD (15 men and 9 women) with levodopa responsiveness and severe motor complications but no severe dementia. They underwent STN DBS at their institution between June 1, 2005, and March 31, 2006. Pain was assessed preoperatively and 8 years after surgery. "Because 13 of the total 24 patients had additional 2-year postoperative data, the serial change between the preoperative and the 2- and 8-year follow-ups after surgery was also evaluated," they note.

During assessments, patients provided a detailed evaluation of their pain during the previous week. The severity of pain was scored according to a scale ranging from 0 (absent) to 10 (maximal pain) in seven body parts (head, neck, trunk, and the upper and lower extremities on each side of the body).

Researchers grouped each pain into one of four categories: dystonic (associated with dystonic movements and postures), musculoskeletal (an aching and cramping sensation of the joints or muscles), radiculoneuritic (localized to near the nerve or root), and central (a bizarre, unexplained sensation of burning or scalding that is usually poorly localized).

The researchers found that the mean off-state total pain score improved from 6.2 at baseline to 4.8 at 8 years. For dystonic pain, the mean pain score went from 6.3 to 8.5. However, said the authors, this score included 2 patients who had severe off-state dystonic pain due to rigidity, and the remaining patients had no dystonic pain.

Five patients had dystonic pain at baseline, and the number of body parts with this pain went down to 12 from 15 at baseline.

For central pain, the mean score decreased from 6.2 to 3.5. The authors described this as a "remarkable" improvement. Nine patients had central pain preoperatively compared with five at follow-up. The number of body parts with this pain decreased from 21 to 11.

Improved central pain suggests that DBS reduces pain by mechanisms other than alleviating motor symptoms, said the authors. Although this mechanism is not completely understood, "It is considered that STN DBS alters sensory processing in the central nervous system, including the basal ganglia," they write.

The mean musculoskeletal pain score went from 5.9 to 4.2 and the radiculoneuritic pain score improved from 6.0 to 2.7.

In terms of pain severity, for the most part, dystonic pain was the most responsive to STN DBS, followed by radiculoneuritic, central, and musculoskeletal pain.

While overall pain scores improved, the number of body parts with pain increased from 48 to 60 over the course of the study.

New Pain

New pain developed in 75% of patients, including 5 patients who experienced no pain at baseline. The number of body parts with newly developed pain was 47. The most common body parts were the lower extremities followed by the upper extremities. The mean scores for new pain was 4.4.

Most of the new pain was musculoskeletal (11 patients), but there was also new central (4 patients), radiculoneuritic (3 patients), and dystonic pain (1 patient).

"Because musculoskeletal pain does not readily respond to the medical and surgical treatment of PD, treatment of its underlying cause should be considered," said the authors.

For the 13 patients who were also assessed at 2 years, the mean score of the off-state pain was 6.9 at baseline; this improved to 3.6 at 2 years and 3.7 at 8 years. This, said the authors, confirms that the beneficial effect of the DBS persisted for 8 years after the surgery.

The number of body parts with pain in the 13 patients was 33 preoperatively, 15 at 2 years, and 30 at 8 years after surgery.

The study was limited in that it was small and had no control group treated medically. As well, it did not correlate pain scores with motor Unified Parkinson's Disease Rating Scale scores, measure the effect of pain on quality of life, or assess mood or cognition (which might have influenced pain perception).

Novel Perspective

According to an accompanying editorial, the new study "provides a novel perspective on the durability of the pain-relieving properties" of STN DBS in patients with PD.

"The authors direct our attention to the fact that musculoskeletal pain may emerge years after DBS, warranting individualized treatment," Pravin Khemani, MD, and Richard Dewey Jr, MD, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, write. "The next step is to pursue a deeper understanding of the mechanism of pain in PD."

The finding that new pain commonly arises years after the DBS procedure "underscores the importance of performing future trials with larger cohorts, longer observational periods and standard methods to enable effective interpretation of outcomes" the editorialists write.

Approached for comment, Michael S. Okun, MD, professor, neurology, University of Florida, and national medical director, National Parkinson Foundation, said it draws attention to an important and often neglected area of PD care and research.

"Typically we will not measure, or even classify, pre-existing pain syndromes and their response to DBS therapy," he told Medscape Medical News.

Dr Okun noted that it's important to understand why some types of pain did not benefit from stimulation. "The emergence of pain postoperatively also needs to be better studied, and likely is related to the disease itself as well as to other comorbidities."

This study was supported by a grant from the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea. The study authors have disclosed no relevant financial relationships. Dr Dewey reported serving as a consultant for Teva Pharmaceuticals, USWorldMeds, Lundbeck, Acadia, Merz, Xenoport, Impax, and GE Healthcare and receiving speakers fees from Teva Pharmaceuticals, USWorldMeds, Lundbeck, and UCB.

JAMA Neurol. Published online March 23, 2015. Abstract Editorial

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