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Effects of pregabalin and duloxetine on neurotransmitters in the dorsal horn of the spinal cord in a rat model of fibromyalgia.
Eur J Pharmacol. 2018 May 15; 827:117-124.EJ

Abstract

Dysfunction of the monoamine systems in the nervous system is associated with the clinical symptoms of fibromyalgia. Reserpine-induced myalgia (RIM) rats are a putative model of fibromyalgia in which muscle pressure thresholds and monoamine content is reduced in the brain and spinal cord. We examined the effects of pregabalin and duloxetine, drugs approved for fibromyalgia treatment, on the levels of extracellular neurotransmitters in the dorsal horn of the spinal cord in RIM rats using microdialysis. Male SD rats were used for all experiments. To generate RIM rats, reserpine was injected at 1 mg/kg subcutaneously once daily for three consecutive days. The pressure threshold of the mid-gastrocnemius muscle was measured using a Randall-Selitto apparatus. Norepinephrine, dopamine, and serotonin were detected using high-performance liquid chromatography with electrochemical detection, and glutamate and γ-aminobutyric acid (GABA) were detected using liquid chromatography-mass spectrometry. The muscle pressure threshold in RIM rats was significantly lower than that in normal rats. While the levels of monoamines and glutamate were lower in the spinal cord of RIM rats than in normal rats, levels of GABA did not markedly differ. Duloxetine increased the levels of all three monoamines in normal and RIM rats in a dose-dependent manner. In contrast, pregabalin only increased norepinephrine levels in RIM rats. These results indicate that while both pregabalin and duloxetine ameliorate muscle pressure thresholds in RIM rats, their effects on the levels of extracellular neurotransmitters in the spinal cord differ considerably.

Authors+Show Affiliations

Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan. Electronic address: tetsuo-kiso@astellas.com.Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan.Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan.Astellas Research Technologies Co., Ltd., 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan.Astellas Research Technologies Co., Ltd., 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29530591

Citation

Kiso, Tetsuo, et al. "Effects of Pregabalin and Duloxetine On Neurotransmitters in the Dorsal Horn of the Spinal Cord in a Rat Model of Fibromyalgia." European Journal of Pharmacology, vol. 827, 2018, pp. 117-124.
Kiso T, Moriyama A, Furutani M, et al. Effects of pregabalin and duloxetine on neurotransmitters in the dorsal horn of the spinal cord in a rat model of fibromyalgia. Eur J Pharmacol. 2018;827:117-124.
Kiso, T., Moriyama, A., Furutani, M., Matsuda, R., & Funatsu, Y. (2018). Effects of pregabalin and duloxetine on neurotransmitters in the dorsal horn of the spinal cord in a rat model of fibromyalgia. European Journal of Pharmacology, 827, 117-124. https://doi.org/10.1016/j.ejphar.2018.03.011
Kiso T, et al. Effects of Pregabalin and Duloxetine On Neurotransmitters in the Dorsal Horn of the Spinal Cord in a Rat Model of Fibromyalgia. Eur J Pharmacol. 2018 May 15;827:117-124. PubMed PMID: 29530591.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of pregabalin and duloxetine on neurotransmitters in the dorsal horn of the spinal cord in a rat model of fibromyalgia. AU - Kiso,Tetsuo, AU - Moriyama,Ai, AU - Furutani,Masako, AU - Matsuda,Ritsuko, AU - Funatsu,Yukiko, Y1 - 2018/03/09/ PY - 2017/09/11/received PY - 2018/02/23/revised PY - 2018/03/07/accepted PY - 2018/3/14/pubmed PY - 2018/10/10/medline PY - 2018/3/14/entrez KW - Amino acid KW - Fibromyalgia KW - Microdialysis KW - Monoamine KW - Pain KW - Spinal cord SP - 117 EP - 124 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 827 N2 - Dysfunction of the monoamine systems in the nervous system is associated with the clinical symptoms of fibromyalgia. Reserpine-induced myalgia (RIM) rats are a putative model of fibromyalgia in which muscle pressure thresholds and monoamine content is reduced in the brain and spinal cord. We examined the effects of pregabalin and duloxetine, drugs approved for fibromyalgia treatment, on the levels of extracellular neurotransmitters in the dorsal horn of the spinal cord in RIM rats using microdialysis. Male SD rats were used for all experiments. To generate RIM rats, reserpine was injected at 1 mg/kg subcutaneously once daily for three consecutive days. The pressure threshold of the mid-gastrocnemius muscle was measured using a Randall-Selitto apparatus. Norepinephrine, dopamine, and serotonin were detected using high-performance liquid chromatography with electrochemical detection, and glutamate and γ-aminobutyric acid (GABA) were detected using liquid chromatography-mass spectrometry. The muscle pressure threshold in RIM rats was significantly lower than that in normal rats. While the levels of monoamines and glutamate were lower in the spinal cord of RIM rats than in normal rats, levels of GABA did not markedly differ. Duloxetine increased the levels of all three monoamines in normal and RIM rats in a dose-dependent manner. In contrast, pregabalin only increased norepinephrine levels in RIM rats. These results indicate that while both pregabalin and duloxetine ameliorate muscle pressure thresholds in RIM rats, their effects on the levels of extracellular neurotransmitters in the spinal cord differ considerably. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/29530591/Effects_of_pregabalin_and_duloxetine_on_neurotransmitters_in_the_dorsal_horn_of_the_spinal_cord_in_a_rat_model_of_fibromyalgia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(18)30146-8 DB - PRIME DP - Unbound Medicine ER -