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Pain Brain

開催日 2014/9/13
時間 17:10 - 19:10
会場 Room F(302)
Chairperson(s) 富永 真琴 / Makoto Tominaga (自然科学研究機構 岡崎統合バイオサイエンスセンター(生理学研究所)細胞生理研究部門 / Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Inst)

Chronic Nociceptive Stimuli Down-regulate the Mesolimbic Dopaminergic Transmission and Aggrevate Pain Sensation

  • S3-F-3-2
  • 成田 年 / Minoru Narita:1,2 
  • 1:星薬科大学 / Dept. Pharmacol., Hoshi Univ., Japan 2:先端生命科学研究センター (L-StaR) / Life Science TOKYO Advanced Research center (L-StaR), Japan 

Pain is a multidimensional experience with sensory-discriminative and motivational-affective components. In the putative emotional circuit, the dopaminergic projection from the VTA to the nucleus accumbens (N.Acc.) participates in appetitive behaviors instructed by conditioned cues. Recent human brain imaging studies have examined differences in activity in the N.Acc. in response to heat stimuli between controls and patients with chronic pain, and have revealed that the N.Acc. plays a role in predicting the value of a noxious stimulus and its offset, and in the consequent changes in the motiva- tional state. On the other hands, clinical studies show that when morphine and mu-opioid agonist analgesics are appropriately used to control pain, actual abuse or addiction does not usually occur. Clinical experience and animal studies support the contention that opioid euphoria and reward are attenuated by pain. We have reported that inflammatory nociception and neuropathic pain result in the suppression of activated mesolimbic dopaminergic transmission evoked by mu-opioids. These results indicate that chronic nociceptive stimuli may induce the functional down-regulation of the rewarding network, leading to the depression and a reduction in abuse potential of mu-opioid analgesics. These phenomena were eliminated in mice that lacked the beta-endorphin gene. Based on our recent optogenetic approach, we found that phasic optical stimulation of VTA dopamine neurons following microinjection of AAV-channel rhodopsin 2 (ChR2) into the VTA of tyrosine hydroxylase (TH)-cre mice temporally suppressed the neuropathic pain-like behavior, whereas phasic optical stimulation of VTA dopamine neurons following microinjection of AAV-halorodopsin (NpHR) into the VTA of TH-cre mice inhibited the antinociception produced by morphine during optical stimulation. These findings provide evidence for the crucial role of the mesolimbic dopaminergic transmission in the possible recovery of decreased pain threshold by chronic nociceptive stimuli. In this symposium, I will also review the molecular mechanisms of pain-induced suppression of the brain reward network associated with opioid dependence.

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