Recently, both electrophysiological studies such as magnetoencephalography (MEG) and hemodynamic studies such as functional magnetic resonance imaging (fMRI) are intensively being used to elucidate underlying mechanisms of human pain and itch perception.
　MEG following A-delta (first pain) and C fiber stimulation (second pain) were similar except for a longer latency for the latter. At first, primary somatosensory cortex (SI) contralateral to the stimulation is activated and then secondary somatosensory cortex (SII), insula, amygdala and anterior cingulate cortex (ACC) in the bilateral hemispheres are activated sequentially. As for findings using fMRI, the stimulation of both C and A-delta fibers activated the bilateral thalamus, bilateral SII, right (ipsilateral) middle insula, and bilateral Brodmann's area (BA)24 ⁄32, with the majority of activity found in the posterior portion of the ACC. However, magnitude of activity in the BA 32 ⁄8 ⁄6, including ACC and pre-supplementary motor area (pre-SMA), and the bilateral anterior insula was significantly stronger following the stimulation of C nociceptors than A-delta nociceptors.
　The cerebral mechanism of itch has been investigated using positron emission tomography (PET) and fMRI. These studies have identified brain regions associated with itch. However, no study has investigated the temporal aspect of the cerebral mechanism of itch because of no itch stimulus useful for electroencephalography (EEG) and MEG recordings. Thus, we developed a new itch stimulus (i. e., electrical itch stimulus). We confirmed that the electrical itch stimulus evoked itch sensation and that itch stimulus-related brain response can be observed using EEG and the stimulus. In addition, the conduction velocity related to the electrical itch stimulus estimated by EEG data was about 1 m/s, indicating that itch sensation evoked by the electrical itch stimulus would be associated with C-fibers. We also performed magnetoencephalography (MEG) recording using the electrical itch stimulus and observed parts of the temporal aspect of itch stimulus-related brain processing. For example, it was suggested that neural information related to itch was transmitted from the contralateral secondary somatosensory cortex /insula (SII /insula) to the ipsilateral SII/insula. In addition, we also observed the activation of the precuneus. Activity of his region was also observed by fMRI study, speculating that the precuneus may be selective for itch. These findings indicate that EEG and MEG recordings using the electrical itch stimulus would be useful to investigate the temporal aspect of the cerebral mechanism of itch.

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　Needle insertion pain is a serious problem for many patients, especially young patients with insulin-dependent diabetes mellitus. Although a reliable assessment method is essential for analyzing and reducing the pain caused by needle insertion, there are very few studies on the measurement of needle pain, because the mechanism of pain is complicated and its assessment is affected by the assessment methodologies. In this study, we assessed flexor reflex responses evoked by insertion of needles into the hind paws of anesthetized rats, and investigated the factors that affect needle pain. We studied the process of needle insertion into the skin using a high-speed microscope and load cell along with a constant insertion speed-controlled device. Needles of two sizes, 27 gauge(G) and 31G (outer diameter: 0.40 and 0.25 mm, respectively), were inserted into the hind paws of anesthetized rats at two velocities. The resultant action potentials evoked by the flexor reflex response in the semitendinosus muscles were recorded by electromyography (EMG). The EMG magnitude evoked by 27G needle insertion was greater than that with the 31G needle, irrespective of insertion speed. Penetration force, which increased as the needle penetrated the plantar skin, might be indirectly related to EMG magnitude. Our method demonstrates that thicker-diameter needles evoke more intense flexor reflex responses, as assessed by EMG in anesthetized rats. This is the first study to assess needle insertion pain in animals, and this method could advance studies on reducing needle insertion pain in humans.

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Opioid-induced nausea and vomiting (OINV) is reported to occur at a lower dose level than the analgesic dosage, whereas it is not clear whether this pharmacological association is also found under the presence of acute pain. In the present study, we investigated the relationship between analgesic dose of morphine and OINV in rat model of postoperative acute pain. A simple laparotomy with a 1-cm midline incision was performed under isoflurane anesthesia (postoperative pain rats). Control rats were given only anesthesia (n=5). Rats were subcutaneously injected with physiological saline (5 ml/kg) or 0.1, 0.5, or 1.0 mg/kg morphine (n=5-6, each dose). The degree of postoperative pain and morphine-induced OINV were quantified using the rat grimace scale (RGS) and kaolin intake, respectively. In laparotomy, but not control, rats, a significant increase in RGS was observed compared to baseline, which was inhibited by morphine in dose-dependent manner; half-maximal analgesic dose was 0.4 mg/kg. One the other hand, administered of morphine increased in kaolin intake dose-dependently in control rats from the lowest dose (0.1 mg/kg) and in postoperative pain rats from 0.5 mg/kg. Furthermore, regression analysis indicates a negative correlation between RGS and kaolin intake in postoperative pain rats. Our results indicate that OINV tends to occur when opioids are used at doses greater than needed to relieve postoperative acute pain.

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