PAIN RESEARCH
Online ISSN : 2187-4697
Print ISSN : 0915-8588
ISSN-L : 0915-8588
21 巻, 3 号
日本疼痛学会誌
選択された号の論文の6件中1~6を表示しています
総説
  • 柿木 隆介, 秋 云海, 野口 泰基, 本田 学, 中田 大貴, 田村 洋平, 田中 悟志, 定藤 規弘, 王 暁宏, 乾 幸二
    2006 年 21 巻 3 号 p. 95-102
    発行日: 2006/08/20
    公開日: 2013/10/24
    ジャーナル フリー
       Acute pain is classified as first and second pain associated with rapidly conducting Aδ fibers and slowly conducting unmyelinated C fibers, respectively. First pain aims at achieving relative safety from the source of injury, whereas second pain, with its strong affective component, attracts longer-lasting attention and initiates behavioral responses in order to limit further injury and optimize recovery. Accordingly, the distinct brain representations for first and second pain should reflect distinct biological functions of both sensations.
       In this study, therefore, an event-related functional magnetic resonance imaging (fMRI) was used to investigate brain processing of the signals ascending from peripheral C and Aδ fibers evoked by phasic laser stimuli on the right hand in humans. The stimulation of both C and Aδ nociceptors activated the bilateral thalamus, bilateral secondary somatosensory cortex (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 anterior cingulate cortex (pACC). However, magnitude of activity in the right (ipsilateral) BA32/8/6, including dorsal parts in the anterior portion of the ACC (aACC) and pre-supplementary motor area (pre-SMA), and the bilateral anterior insula was significantly stronger following the stimulation of C nociceptors than Aδ nociceptors. It was concluded that the activation of C nociceptors, related to second pain, evokes different brain processing from that of Aδ nociceptors, related to first pain, probably due to the differences in the emotional and motivational aspects of either pain, which are mainly related to the aACC, pre-SMA and anterior insula.
  • 中塚 映政, 古賀 秀剛, 藤田 亜美, 井上 和秀, 熊本 栄一
    2006 年 21 巻 3 号 p. 103-110
    発行日: 2006/08/20
    公開日: 2013/10/24
    ジャーナル フリー
       The spinal dorsal horn is the first central site for sensory processing and can be divided into structurally and functionally distinct lamina regions. Superficial dorsal horn neurons including lamina II neurons receive synaptic inputs from fine primary afferents that mainly carry nociceptive signals from the periphery. Deep dorsal horn neurons, especially lamina V neurons, receive convergent sensory inputs from both nociceptive and non-nociceptive primary afferents. We examined a role of P2X receptors in modulating excitatory synaptic transmission by using patch-clamp recordings from dorsal horn neurons of the rat spinal cord. Distinct subtypes of P2X receptors were located at central terminals of primary afferents that innervate onto lamina II and lamina V neurons. On activation, these P2X receptors produced glutamate release enhancements in a different fashion from each other. In lamina II neurons, the modulation of glutamate release by presynaptic P2X receptors was mainly transient. In contrast, the P2X receptor-mediated modulation of glutamate release was relatively long-lasting in lamina V neurons. Pharmacologically, both of the transient and long-lasting types of modulation were blocked by PPADS. The transient modulation in lamina II neurons was not observed in the presence of TNP-ATP, suggesting an involvement of homomeric P2X3 receptors. The P2X receptor-mediated long-lasting modulation of glutamate release in lamina V neurons remained in the presence of TNP-ATP. In addition, the removal of P2X3 receptor-expressing afferent terminals by the targeting toxin saporin-conjugated IB4 or by surgical removal of superficial dorsal horn did not affect the P2X receptor-mediated long-lasting modulation of glutamate release in lamina V neurons. The pharmacological profiles appeared to be consistent with the involvement of slowly desensitizing P2X4+6 receptors. Differences among P2X-expressing afferent fibers innervating lamina II and lamina V neurons were also seen in terms of capsaicin sensitivity. P2X-expressing afferent central terminals in the lamina II were derived from capsaicin-sensitive primary afferents, while those in the lamina V were from capsaicin-insensitive A primary afferents. Since P2X3-expressing afferent central terminals directly make synapses with lamina II neurons,the inputs from these afferent terminals could forward excitatory synaptic activities. On the contrary, the activities conveyed to lamina V neurons from P2X3-expressing primary afferents were polysynaptic; these inputs together with monosynaptic inputs from P2X-expressing and capsaicininsensitive afferents were shown to converge on lamina V neurons. These results indicate that distinct subtypes of P2X receptors are expressed in central terminals of primary afferents innervating onto superficial and deep dorsal horn neurons, and modulate glutamate release in a different manner. These presynaptic actions may serve to understand P2X receptor-mediated modulation of various sensations.
原著
  • 貴島 晴彦, 齋藤 洋一, 加藤 天美, 平山 東, 押野 悟, 平田 雅之, 大崎 康宏, 畑澤 順, 吉峰 俊樹
    2006 年 21 巻 3 号 p. 111-115
    発行日: 2006/08/20
    公開日: 2013/10/24
    ジャーナル フリー
       Motor cortex stimulation (MCS) has been reported to control chronic deafferentation pain successfully. However, the detailed mechanisms of this action have not been made clear. To investigate the possible neural pathways involved in this effect, we measured pre- and post-MCS regional cerebral blood flow (rCBF) using positron emission tomography (PET).
       Six patients with intractable pain in their left upper extremities were studied. All six were right handed and subdural electrodes were surgically placed over the right primary motor cortex. The rCBF was measured using PET with H215O during pre-MCS conditions of pain and post-MCS conditions of reduced pain. The PET images were analyzed with SPM99 statistical parametric mapping software. The rCBF during pain reduced conditions after MCS increased in left posterior thalamus, left posterior insula, right orbitofrontal cortex, and the left caudal anterior cingulated, when compared to that of the pre-MCS conditions of pain. This result suggests that MCS modulates both pain gait and emotion related pain.
  • 池本 竜則, 牛田 享宏, 谷口 慎一郎, 谷 俊一, 森尾 一夫, 佐々木 俊一, 田中 茂樹
    2006 年 21 巻 3 号 p. 117-125
    発行日: 2006/08/20
    公開日: 2013/10/24
    ジャーナル フリー
       Using functional magnetic resonance imaging (FMRI) technology, we investigated the difference of pain related brain cortical activation derived from noxious stimulation to the skin and muscular tissue. Ten healthy volunteers who have no history of brain vascular disease were enrolled in this study. A cutaneouos pain was provoked by isotonic (0.9%) saline injection into intradermal space on right lower leg through 24G plastic catheter, and a muscle pain was provoked by hypertonic (3%) saline injection into right tibialis anterior muscle. We used event-related FMRI to measure brain activity during each injection. Visual analogue scale (VAS) was used to quantify pain intensity and unpleasantness, and pain quality was assessed with several verbal descriptions. Results: Pain unpleasantness rating was higher in the muscle pain compared to the cutaneous pain,despite the same pain intensity rating. The cutaneous pain had more acute pain onset than the muscle pain. Pain duration after stimulation was short in the cutaneous pain, but long in the muscle pain. The extent of the painful region tended to be larger with the muscle pain, but there was no statistical significance. Evoked FMRI response from the cutaneous pain showed distinct brain activation in the inferior and superior parietal cortex (BA: Brodmann area 5/7/40), primary and secondary somatosensory cortex (S1 & S2), insula, supplementary motor area (SMA, BA6), posterior cingulate cortex and cerebellum. On the other hand, FMRI response from muscle pain showed distinct brain activation mainly in the contralateral insula. These results suggest that the parietal lobe including the S1 is the essential area for cognition of sharp and well-localized pain conditions such as cutaneous pain, and may not be essential for cognition of diffuse pain derived from muscular tissue.
  • 川田 倫子, 牛田 享宏, 池内 昌彦, 川上 照彦, 山中 紀夫, 池本 竜則, 谷 俊一, 小松 誠
    2006 年 21 巻 3 号 p. 127-132
    発行日: 2006/08/20
    公開日: 2013/10/24
    ジャーナル フリー
       Hip joint associated pain is known to distribute widely in affected thigh or lower leg and generally not restricted in hip joint area.However detail feature of hip joint associated referred pain is not sufficiently clarified. Therefore the aim of this study is to characterize the types of distribution of hip joint related pain and to give our opinion about underlying neurophysiological mechanisms of hip joint referred pain. Of 36 severe osteo-arthritis joints, 83% of the joints showed remote pain area and 18% of the joints showed pain restricted only in inguinal area. Fourteen percent of the joints had far remote pain in lower leg area. L5 root block study was conducted in 7 cases. In all cases remote referred pains were attenuated at least 2 or 3 days and long lasting pain improvement was achieved in one case. These results suggest that referred pain observed in severe hip osteoarthritis cases may initially triggered by hip joint itself but prolonged referred muscle pain may become a possible generator for triggering and maintaining of mal-pain circuit.
  • 小泉 修一, 藤下 加代子, 津田 誠, 井上 和秀
    2006 年 21 巻 3 号 p. 133-139
    発行日: 2006/08/20
    公開日: 2013/10/24
    ジャーナル フリー
       ATP acts as an intercellular messenger in a variety of cells.Here we characterized the Ca2+ wave propagation mediated by extracellular ATP in cultured normal human epidermal keratinocytes (NHEKs) also co-cultured with mouse dorsal root ganglion (DRG) neurons. We also asked about physiological consequence of the ATP-mediated communication in relation to pain by behavioral analysis. Pharmacological characterization showed that NHEKs express functional metabotropic P2Y2 receptors. When a cell was gently stimulated with a glass pipette, an increase in the intracellular Ca2+ concentration ([Ca2+]i) was observed, followed by propagating Ca2+ waves in neighboring cells in an extracellular ATP-dependent fashion. Using an ATP-imaging technique, the release and diffusion of ATP among NHEKs were confirmed. DRG neurons are known to innervate the epidermis that is mainly composed of keratinocytes. In the co-culture of NHEKs and DRG neurons, mechanical stimulation-evoked Ca2+ waves in NHEKs evoked the [Ca2+]i elevation in adjacent DRG neurons,which was also dependent on extracellualr ATP and the activation of P2Y2 receptors. Extracellular ATP is a dominant messenger that forms intercellular Ca2+ waves in NHEKs. In addition, Ca2+ waves in NHEKs could produce a [Ca2+]i elevation in DRG neurons, suggesting dynamic cross talk between skin and sensory neurons mediated by extracellular ATP. Next we investigated a physiological consequence of the ATP-mediated communications. Injection of the P2Y2 and P2Y4 receptor agonist uridine 5'-triphosphate (UTP) into plantar surface in rats produced the mechanical allodynia in a concentration-dependent manner. The UTP-induced mechanical allodynia was inhibited by the P2 receptor antagonist PPADS (pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate) or antisense oligonucleotide for P2Y2 receptors. Taken together, ATP is a key molecule that mediates pain signaling from skin to sensory neurons.
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