The information of nociceptive stimuli given to the periphery is transmitted through primary-afferent fibers to the spinal dorsal horn, especially substantia gelatinosa (SG; lamina II), which plays a pivotal role in regulating the nociceptive transmission. The SG neurons receive (glutamatergic) excitatory and (GABAergic and glycinergic) inhibitory transmissions in a mono- or poly-synaptic manner through myelinated Aδ and unmyelinated C fibers. Many of extrinsic and intrinsic analgesics inhibit the excitatory transmission and/or enhance the inhibitory transmission, both of which modulations are mediated by G-protein coupled metabotropic neurotransmitter receptors. Monosynaptic Aδ-fiber and C-fiber transmission inhibitions by many analgesics are different in extent from each other. The activation of metabotropic neurotransmitter receptors expressed in postsynaptic SG neurons produces a membrane hyperpolarization. These actions result in a relief of pain sensation. The central terminals of the primary-afferent neurons express transient receptor potential (TRP) channels, the activation of which increases the spontaneous release of _L-glutamate to the SG neurons; this may produce a nociception. Nerve conduction in primary-afferent neurons is inhibited by metabotropic neurotransmitter receptor agonists, such as opioids and α₂ adrenoceptor agonists, without receptor activation, and also by TRP agonists in a manner independent of the channels. Such a conduction inhibition may produce a local anesthetic effect. It is concluded that nociceptive transmission to the SG from periphery is regulated by modulating synaptic transmission and nerve conduction through an action of metabotropic neurotransmitter receptor and TRP agonists.

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　We have newly developed a low-powered magnetic stimulator (MS) that is characterized by two different frequency modes: 2 kHz (low frequency) and 83 MHz (ultra-short wave). It is suggested that MS reduces rat neuropathic pain associated with the prevention of neuronal degeneration. However, little is known about certain mechanisms of MS, at least, applicable value of the analgesic approaches in clinical situation. Thus, we aimed to determine the analgesic effects of MS in human with shoulder stiffness.
　We recruited volunteers with shoulder stiffness (MS was applied once for 10 min.) and with acute pain (MS was applied once a day (10 min period) for 9 days. The trial study on analgesic effects in human of new magnetic therapeutic instrument (Angel Touch^®) were examined. We examined safety of MS based on electrocardiographic testing and body surface temperature. By using the heart rate on the electrocardiogram, we used FFT analyzer to analyze low frequency components (LH: 0.05 - 0.15Hz) and high frequency components (HF: 0.15 - 0.45 Hz). Muscle shoulder stiffness has been improved by the continued irradiation without a thermal action.
　Based on the present study, we suggest that MS has beneficial analgesic effects in human, and that MS will be a useful approach to treatment for neurodegenerative disorder because it may relieve pain via improvement of functional modulation of pain-emotional system.

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　The validity of animal pain assessment still remains a matter of debate. In the present study, we hypothesized that pin-evoked a complex hyperalgesic-type response is a more clinically relevant indicator for analgesic effect than simple withdrawal from von Frey tactile stimulation in rats after peripheral nerve injury. To test this hypothesis, we investigated the effects of pregabalin and NK₁ antagonist CP-99994, as an example of a standard neuropathic pain treatment and an analgesic active in animal models but not in neuropathic pain patients, respectively. Administration of pregabalin (30 mg/kg, p.o.) resulted in analgesic effects in both von Frey and pin test with similar potency. On the other hand, CP-99994 (100 mg/kg, p.o.) showed analgesic effects in von Frey test, but not any effects in pin test. Our results indicated that pin-evoked a complex hyperalgesia-type response is one of translational and appropriative analgesic measurements in rats after peripheral nerve injury.

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