Dopamine (DA) is well known as a neurotransmitter and neuromodulator in the brain, not only as a precursor in the synthesis of other catecholamines. DA controls a variety of functions including locomotor activity, cognition, emotion, positive reinforcement, food intake, and endocrine regulation. Compared with the enormous literature devoted to DA actions in the brain, little is known about the roles of DA in the spinal cord. To elucidate the mechanisms of antinociception mediated by the dopaminergic descending pathway in the spinal cord, we investigated the actions of DA on substantia gelatinosa (SG) neurons by in vivo whole-cell patch-clamp methods. In the voltage-clamp mode (V_H = -70 mV), the application of DA induced outward currents in about 70% of SG neurons tested. DA also significantly suppressed the frequency and amplitude of glutamatergic spontaneous excitatory postsynaptic currents (EPSCs). DA-induced outward current was observed in the presence of TTX or a non-NMDA receptor antagonist, CNQX. DA also significantly decreased the frequency of miniature EPSCs in the presence of TTX. These results suggest that DA has both presynaptic and postsynaptic inhibitory actions on synaptic transmission in SG neurons. The DA-induced outward current was completely blocked by either GDP-β-S in the pipette solution or by perfusion of a non-selective K⁺ channel blocker, Ba²⁺. Moreover, the DA- induced outward currents were mimicked by a selective D2-like receptor agonist, quinpirole, but not by a D1-like receptor agonist, SKF 38393. In addition, the DA-induced outward current was attenuated by a selective D2-like receptor antagonist, sulpiride. These findings suggest that the DA- induced outward current is mediated by G-protein-activated K⁺ channels through D2-like receptors. Furthermore, we investigated whether DA has direct antinociceptive actions into noxious and innocuous stimuli on the receptive field skin of recording SG neuron. The results showed that DA produced direct analgesic effects in SG neurons to both noxious and innocuous stimuli to the skin. These findings suggest the dopaminergic descending pathway has an antinociceptive effect via D2-like receptors on SG neurons in the spinal cord.

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　Objective. We studied the surgical results and indications of spinal cord stimulation and thalamic surgery for the purpose of treating central post-stroke pain (CPSP).
　Subjects and Methods. CPSP due to unilateral cerebrovascular disease (CVD) lesion was studied in 17 subjects. Pain was localized on the limb (localized type CPSP) in 7 cases and distributed on the hemibody (diffuse type CPSP) in the other 10 cases. All cases of localized type CPSP were treated by epidural spinal cord stimulation. For cases with diffuse type CPSP, stereotactic Vim-Vcpc thalamotomy was performed in 6 cases and thalamic Vim-Vcpc stimulation in 4 cases using depth micro-recording. Evoked pain was dominant in the former and continuous, sometimes intermittent, pain was dominant in the latter. Prior to the operation, we studied somatosensory evoked potentials (SEP) in all cases of localized type CPSP and in 6 cases with diffuse type CPSP treated by thalamotomy. In cases involving thalamic surgery, electrophysiological data obtained during surgery included background neural activity (BNA), sensory response (SR) and burst discharge (burst), and responses to micro-stimulation in the thalamic sensory nucleus.
　Results. In 7 cases with localized type CPSP treated by spinal cord stimulation, sufficient pain relief was achieved in 4 cases, moderate in 2 cases and fair in one case. In 10 cases with diffuse type CPSP, good was achieved in 3, moderate in one, fair in 2 out of 6 cases treated by thalamotomy, and good in 2 and moderate in 2 out of 4 cases treated by thalamic stimulation. With the exception of one “fair" respondent to spinal cord stimulation, we recognized definite SEP originating in the sensory cortex (N20). However, SEPs were flat in 4 cases and the amplitude of N20 markedly decreased in the other 2 cases treated by thalamotomy. Using results taken from the electrophysiological study during thalamic surgery, these patients could be classified into 3 groups. In group A (3 cases), we found SR frequently and rarely encountered bursts in a wide area of the thalamic sensory nucleus. In group B (5 cases), we encountered marked burst discharges with high amplitude and of various duration. These were recogn-ized around decreased or voided areas of thalamic neural activity. In 2 cases, which were classified as group C, we found a decrease of BNA, few bursts and no SR in the sensory thalamus. We found response to micro-stimulation in all groups. Pain control was achieved by thalamic surgery in both group A and B.
　Conclusions. Spinal cord stimulation proved to be an effective treatment for localized type CPSP in those cases in which the lemniscal system was preserved. In cases with diffuse type CPSP, we found both dysfunction of the lemniscal system and functional change of the spino-thalamic system. We were able to ameliorate this intractable pain by stereotactic Vim-Vcpc thalamic surgery in those cases in which the spino-thalamic system had been preserved or was hyperactive.

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　Eugenol (4-allyl-2-methoxyphenol), which is contained in several plants including clove and bay leaves, has been widely used as an analgesic and anti-inflammatory drug in the dental clinic. Furthermore, eugenol has a general anesthetic effect, and produces sedation and the reduction of convulsion threshold. These benefits have been partly attributed to the effects of eugenol on neural tissues. Eugenol depresses the conduction of action potential in nerve fibers and thus serves as a local anesthetic. Voltage-gated Na⁺, Ca²⁺ and K⁺ channels are inhibited by eugenol in rat trigeminal ganglion neurons or dorsal root ganglion (DRG) neurons. As expected from the fact that eugenol and capsaicin share the vanilloid moiety in chemical structure, eugenol activates transient receptor potential (TRP) V1 channels, nonselective cation channels, in rat DRG neurons. Although eugenol is suggested to affect synaptic transmission in the central nervous system, to our knowledge, this has not yet been fully examined. The present study investigated how eugenol affects glutamater-gic spontaneous excitatory transmission in substantia gelatinosa (SG; lamina II of Rexed) neurons of adult rat spinal cord slices by use of the blind whole-cell patch-clamp technique. Bath-applied eugenol reversibly enhanced spontaneous excitatory transmission in SG neurons in a concentration-dependent manner in a range of 1 - 5 mM. This action was due to a large increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) with a small increase in the amplitude. Eugenol also produced an outward current at −70 mV. These actions of eugenol were seen by its repeated application and resistant to a voltage-gated Na⁺-channel blocker tetrodotoxin (0.5 µM). The effect of eugenol (5 mM) on sEPSC frequency was unaffected by a TRPV1 channel antagonist capsazepine (10 µM) while inhibited by a non-selective TRP channel antagonist ruthenium red (300 µM). On the other hand, the eugenol-induced outward current was not affected by both of the antagonists. It is concluded that eugenol activates TRP channels other than TRPV1 channels in the SG, leading to an increase in the spontaneous release of L-glutamate to SG neurons and that eugenol also produces a membrane hyperpolarization which is not mediated by TRP channels. The former action could be involved in producing nociception.

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　Objective. To determine which method provides superior pain relief and recovery from anesthesia while minimizing adverse effects in the immediate postoperative period.
　Methods. We studied 70 patients undergoing gynecologic laparotomy. Anesthesia was induced with propofol and remifentanil. After tracheal intubation facilitated with vecuronium or rocuronium, anesthesia was maintained with sevoflurane and remifentanil. Patients were randomly assigned to receive 8 µg/kg of fentanyl at the start of surgery (early-bolus group) or 6 µg/kg of fentanyl at 60 min before the anticipated end of surgery (late-bolus group). At the end of surgery, the times from discontinuation of sevoflurane until patient response to verbal commands and until extubation were recorded as indicators of recovery from anesthesia. Hemodynamic parameters, pain score, sedation grade, and incidence of side effects were evaluated at 0, 5, 10, 15, and 30 min after entering the post-anesthesia care unit (PACU).
　Results. A longer recovery time from anesthesia was required in the late-bolus group compared with the early-bolus group, whereas mean pain score was significantly lower in the late-bolus group compared with the early-bolus group. Furthermore, mean dose of fentanyl administered in the PACU was significantly higher in the early-bolus group compared with the late-bolus group. Sedation grade and incidence of adverse effects were similar between the groups.
　Conclusion. Administration of 6 µg/kg fentanyl at 60 min before the anticipated end of surgery during remifentanil-based anesthesia provided superior postoperative analgesia in the immediate postoperative period as compared with 8 µg/kg fentanyl administered at the start of surgery.

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　Hind-paw scratching elicited by an intradermal injection of serotonin (5-HT) into the nape of the neck is used increasingly as a rodent itch model. In the present study, we examined if the itch model was useful tool for studying itch sensation in humans, especially for its negative affective aspects. Using adult male Sprague-Dawley rats, we first confirmed that intradermal 5-HT injection evokes hind-paw scratching as a measure of sensory aspects of itch sensation. Second, we evaluated negative affective aspects by combining 5-HT treatment with the conditioned place aversion paradigm. In both experiments, the rats were injected with either 5-HT or saline (vehicle) into the nape of the neck, and also another set of rats were injected with 5-HT into an area of the back where the rats cannot reach with the hind-paws to remove the itch by scratching. 5-HT injection into either the nape of the neck or the back significantly increased scratching compared to vehicle injection although scratching elicited by 5-HT into the back was significantly less when compared to that into the nape of the neck. In the place-conditioning, 5-HT injections, irrespective of the injection site, produced a significant place aversion compared to vehicle injection, suggesting that itch produces an aversive sensation whether or not scratching temporarily relieves it. These data provide supporting evidence that the rodent itch model is a reliable method to study itch sensation in humans.

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