The A11 dopaminergic cell group is the only group among the A8-A16 dopaminergic cell groups that includes neurons innervating the spinal cord, and a decrease in dopaminergic transmission at the spinal cord is thought to contribute to the pathogenesis of restless legs syndrome. However, the mechanisms regulating the neuronal activity of A11 dopaminergic neurons remain to be elucidated. Unraveling the neuronal composition, distribution and connectivity of A11 neurons would provide insights into the mechanisms regulating the spinal dopaminergic system. To address this, we performed immunohistochemistry for calcium-binding proteins such as calbindin (Calb) and parvalbumin (PV), in combination with the retrograde tracer Fluorogold (FG) injected into the spinal cord. Immunohistochemistry for Calb, PV, or tyrosine hydroxylase (TH), a marker for dopaminergic neurons, revealed that there were at least three types of neurons in the A11 region: neurons expressing Calb, TH, or both TH and Calb, whereas there were no PV-immunoreactive (IR) cell bodies. Both Calb- and PV-IR processes were found throughout the entire A11 region, extending in varied directions depending on the level relative to bregma. We found retrogradely labeled FG-positive neurons expressing TH, Calb, or both TH and Calb, as well as FG-positive neurons lacking both TH and Calb. These findings indicate that the A11 region is composed of a variety of neurons that are distinct in their neurochemical properties, and suggest that the diencephalospinal dopamine system may be regulated at the A11region by both Calb-IR and PV-IR processes, and at the terminal region of the spinal cord by Calb-IR processes derived from the A11 region.
We report on two cases of patients with chronic pain treated with opioid analgesics. They did not continue their treatment with opioid because of side effects. An 88 year-old female complained of low back and leg pain caused by lumbar spinal canal stenosis. She also complained of dizziness, nausea and appetite loss after a course of weak oral opioid was administered. We thought it necessary to improve her general condition and digestive sickness following treatment for pain, and administered 5 g/day of hangebyakujutsutemmato. After the administration of this hangebyakujutsutemmato, her general condition improved, and we could administer various analgesics. A 62 year-old female complained of dull headache, right neck pain and stiffness of tear and mouth due to fibromyalgia and collagen disease dating back several years. Her pain was reduced by the combined administration of a strong opioid and an immunosuppressive agent. However, she complained of severe dizziness, nausea and appetite loss after the commencement of drug therapy. Her general condition improved markedly, through the administration of 5 g/day of hangebyakujutsutemmato, and she was able to continue her treatment of chronic pain without deleterious events. In conclusion, in patients treated with opioids for chronic pain, dizziness, dull headache, nausea, vomiting and loss of appetite is often seen. Therefore, we emphasize that the combined administration of hangebyakujutsutemmato and opioids can be beneficial for the treatment of chronic pain patients. chronic pain, opioid, hangebyakujutsutemmato
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