The mechanisms for a novel magnetic stimulator, Angel Touch® in rat chronic pain - Spinal and supra-spinal descending system

Hironori Sasaki, Yoshiteru Kagawa, Satoru Yamamoto, Takahiro Kakeda, Seiko Yasuda, Toshizo Ishikawa, Mitsuharu Nishi

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1 Citation (Scopus)

Abstract

Although magnetic stimulation (MS) has a potential effect to prevent various CNS diseases including depression and sustained pain, the certain mechanisms are not fully understood. Recent studies demonstrated that the MS can induce Ca2+ influx into neuron and glia in cultured cells lead to increased intracellular phosphorylation. In addition, we have demonstrated that MS mimics rat neuropathic pain associated with prevention of neuronal degeneration. In the present study, we thus, aimed to elucidate the action of MS in relation to the modulation of spinal neuro-glia interaction and descending inhibitory system. In order to provide rat chronic pain models, male SD rats were subjected to sciatic nerve ligation with a 4-0 silk thread. For intrathecal drug injection PE-10 catheter was implanted into cistern magna. The MS is battery based low power apparatus and is characterized by two different modes of frequencies, 2 KHz and 83 MHz. The two experimental series were carried out as 1) CCI treatment and 2) descending systems. Rats were given MS for 10 min. from day 7 to day 14 after CCI. The probe of MS was close to the skin where is located in sciatic nerve ligation. The paw withdrawal latency (PWL, sec) evoked by thermal stimuli was measured from day 3 after CCI. After removal of spinal tissue fixed with formalin perfusion, the imunohistochemistry for microglial (Iba-1) or astrocytic (GFAP) activation was performed followed by microscopical analysis. In addition, the spinal microdialysis was performed to see the effect of MS on supra-spinal 5-HTergic systems. We measured 5-HIAA as reflection of 5-HT release by MS stimulation without nerve injury. We employed one-way ANOVA and Turkey for multi-comparison among groups. p<0.05 was considered to be significant. Following CCI the rats showed the decrease in PWL from day 3 lasted over day 14. With MS treatment, the decrease in PWL was significantly reduced during day 10 to day 14. This effect of MS treatment was antagonized by injecting p38-MAPK inhibitor (SB203580) or JNK-1 inhibitor (SP600125) on day 14. Decrease in GFAP immuno-reactivity after CCI was reduced by MS. Moreover, MS given to non-CCI rats showed a transient increase in spinal 5-HIAA. Although the trans-cranial magnetic stimulation is respected to prevent various types of CNS diseases by inducing c-fos and neurotrophic factors in animal studies, its detailed mechanism is still not understood. In the present study, we demonstrate that a novel magnetic stimulator (Angel Touch® ) trans-cutaneously exposed can ameliorate neuropathic pain via mechanisms of the activation of spinal astrocyte related to p38-MAPK and JNK activations and also descending 5-HTergic inhibitory systems. These results firstly indicated that MS has potential effects on hyperalgasia via activation of the spinal neuron-glia interaction and descending inhibitory systems.

Original languageEnglish
Pages (from-to)273-283
Number of pages11
JournalJapanese Pharmacology and Therapeutics
Volume38
Issue number3
Publication statusPublished - 2010 Apr 29
Externally publishedYes

Keywords

  • Magnetic stimulation
  • Neuropathic pain
  • Neurotrophic factor
  • P38-MAPK

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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