Mechanisms of effective drugs for management of neuropathic pain relationship between activation of descending inhibitory systems and pharmacologic plasticity

2014 Fiscal Year Final Research Report

• Project/Area Number: 23390373
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Gunma University
• Principal Investigator: OBATA Hideaki 群馬大学, 医学(系)研究科(研究院), 准教授 (20302482)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: ノルアドレナリン / セロトニン / 下行性抑制系 / 神経障害性疼痛 / 薬剤可塑性 / 脊髄 / ラット

Outline of Final Research Achievements

Brainstem-spinal descending noradrenaline (NA) and serotonin (5-HT) systems suppress nociceptive signals from primary afferent neurons to the spinal dorsal horn. These inhibitory systems may play an important role in mechanisms of analgesic action of several drugs such as opioids and antidepressants that are frequently used for management of neuropathic pain. Several lines of evidence suggest that function of the descending inhibitory systems changes dynamically after nerve injury. In this reserch, we demonstrated followings. First, activation of spinal α2-adrenoceptors releases acetylcholine after nerve injury, which results in increasing efficacy of analgesia of antidepressants in neuropathic pain. Second, opioids including morphine activate descending serotonergic neurons and increase 5-HT in the spinal cord. The increased 5-HT facilitate neuropathic pain via spinal 5-HT3 receptors. Therefore, efficacy of opioids for neuropathic pain is less than that for acute pain.

Free Research Field

麻酔学