α₂ adrenoceptors are widely distributed in the central nervous system and involved in various physiological functions such as analgesia, hypnosis, amnesia and circulation. α₂ agonists generally used as sedative agents, are also known to have analgesic properties. Previous in vitro studies have shown detailed cellular actions of α₂ agonists by using electrophysiological analyses. In the locus coeruleus (LC) of the brain stem, α₂ agonists are thought to inhibit LC neuronal activity to exert their sedative actions. In the spinal cord, dexmedetomidine (DEX), a highly selective α₂ agonist, directly hyperpolarized substantia gelatinosa (SG, lamina II of the spinal cord) neurons by activating α_2A and α_2C adrenoceptors. Little is known, however, how systemically administered α₂ agonists modulates noxious transmission at the synaptic level in vivo. We made in vivo whole-cell patch-clamp record­ings from SG neurons in adult anesthetized rats and examined analgesic action of systemically administered DEX. Contrary to our expection, intravenous administration of DEX at doses of sedative range did not induced any hyperpolarization in all SG neurons tested. Interestingly, DEX at doses below sedative range dramatically enhanced spontaneous inhibito­ry postsynaptic currents (IPSCs) in most of SG neurons tested. This facilitatory action of DEX was completely disappeared in spinalized rats, and spinal application of prazosin, an α₁ antagonist, inhibited the facilitation of spinal IPSCs by DEX. These results suggest that systemically administered DEX at doses below sedative range paradoxically enhances descending noradrener­gic inhibitory pathway and results in facilitation of inhibitory synaptic transmission in the spinal dorsal horn. Our findings provide a new insight into the usefulness of α₂ agonists for therapeutic intervention against acute and chronic pain.

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　Coordinated movement of the bladder, urethra and external urethral sphincter in the lower urinary tract (LUT) is essential for the bladder filling and voiding. The activations of these organs are precisely controlled by the central nervous system including the spinal cord, through the peripheral sympathetic (hypogastric), parasympathetic (pelvic) and somatic (pudendal) nerves. Preganglionic neurons in sacral parasympathetic nucleus (SPN) of the spinal cord play an important role of in regulating different pelvic organ function including micturition and defecation. In this study, we developed an in vivo patch-clamp recording technique from spinal preganglionic neurons to investigate how the spinal cord controls the LUT function at the synaptic level. Slice patch-clamp recordings from SPN neurons were also used to analyze excitatory monosynaptic inputs from primary afferent fibers. Preganglionic neurons in SPN showed tonic or phasic firing properties in response to current pulse injections and SPN neurons received monosynaptic Aδ and C fiber-mediated excitatory synaptic inputs. Intravesical pressure was synchronously changed with neuronal bursting of sacral spinal pre­ganglionic neurons in vivo. The newly developed recording technique is useful for elucidating the detailed synaptic mechanism for spinal control of LUT function.

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   Objects: It has been found that the orofacial region exhibits a great deal of referred pain. Substantial chronic pain results from the inability to identify the primary cause of pain. In acupuncture therapy, when the primary cause is not found, treatment to hands or feet is used for orofacial pain in addition to topical treatments. However, many questions remain regarding the therapeut­ic mechanism. Therefore, we examined the effects of electro­acupuncture (EA) on mustard oil-induced orofacial pain in rats and also characterized the effects of naloxone in this model.
   Methods: A total of 39 adult male Sprague Dawley rats (250 - 400 g) were randomized into three groups: a control [CONT] group, an EA group, and an EA + naloxone [NAL] group. Activity was recorded from functionally identified single nociceptive neurons in the trigeminal subnucleus caudalis for which mechanoreceptive fields [RFs], mechanical activation thresholds, and responses to noxious stimuli were tested in anesthetized rats. Ten minutes after 5％ mustard oil (MO) injection into the masseter muscle, EA and NAL group rats received 2 Hz EA for 15 min. NAL group rats were injected with naloxone intravenously 5 min before the MO injection.
   Results: In the CONT group, RFs and responses were significantly increased and the mechanical activation thresholds were deceased within 35 min of MO injection, and then gradually returned to baseline. In the EA group, however, the RFs, responses, and thresholds recovered to baseline soon after EA. In the NAL group, the time-course of RFs, responses, and thresholds were similar to those of the CONT group.
   Conclusion: The results suggest that EA is effective in reducing MO-induced orofacial pain via activation of the endogenous opioid system.

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　Some validated methods for assessing pain in laboratory animals are currently available. However, it remains to be determined whether these methods are also applicable for aged animals. Recently, grimace scale (GS) was developed for pain assessment based on facial expressions, and can effective­ly evaluate animal spontaneous pain. In the present study, we investigat­ed that accuracy and reliability of the rat grimace scale (RGS) in aged rats. Six coders were trained with the RGS training manual. Unlabeled 80 facial images of which half were with no pain (baseline), the other half were with pain (2 - 4 h after laparotomy) were randomly assigned and then scored by the coders. A high degree of the reliability was found with an overall intra-class correlation coefficient value of 0.92. The average ac­curacy of pain detection assessed by coders’ dichotomous judgment of “global pain” or “no pain” was sufficiently high with a correct classification rate of 84.6％. Furthermore, a single subcutaneous administration with morphine (1.0 mg/kg) resulted in decrease of RGS at 4 h after laparotomy. These results suggested that RGS is a useful method for assessing spontaneous pain after laparotomy in aged rats.

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