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

Eur J Neurosci. 2015 Aug;42(4):2061-9. doi: 10.1111/ejn.12992. Epub 2015 Jul 14.

Abstract

Chronic pain is a major complaint for up to 85% of Parkinson's disease patients; however, it often not identified as a symptom of Parkinson's disease. Adequate treatment of motor symptoms often provides analgesic effects in Parkinson's patients but 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 von Frey, tail-flick and hot-plate tests. Tests were done during and off subthalamic stimulation at 50 and 150 Hz to assess its effects on sensory thresholds. The 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 150 Hz increased mechanical (left paw; P < 0.01) and thermal thresholds in 6-hydroxydopamine-lesioned rats (hot-plate test: 150 Hz, P < 0.05, 50 Hz, P < 0.01). Interestingly, during von Frey testing, low-frequency stimulation provided a more robust improvement in some 6OHDA lesioned rats, while in others, the magnitude of improvement on high-frequency stimulation was greater. 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.

Keywords: Parkinson's disease; hot plate test; mechanical allodynia; thermal hyperalgesia; von Frey test.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Agents / toxicity
  • Animals
  • Deep Brain Stimulation / methods*
  • Disease Models, Animal
  • Functional Laterality
  • Hyperalgesia / etiology
  • Hyperalgesia / therapy*
  • Male
  • Oxidopamine / toxicity
  • Pain Threshold / drug effects
  • Pain Threshold / physiology*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / complications
  • Parkinsonian Disorders / therapy
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Statistics, Nonparametric
  • Subthalamic Nucleus / physiology*
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Adrenergic Agents
  • Oxidopamine
  • Tyrosine 3-Monooxygenase