Centre for Neuroplasticity and Pain, SMI, Department of Health Science and Technology, School of Medicine, Aalborg University, Aalborg, Denmark.
Department of Anaesthesiology and Pain Medicine, Hyogo Medical University, Nishinomiya, Hyogo, Japan.
Scand J Pain. 2023 Sep 15;23(4):743-750. doi: 10.1515/sjpain-2023-0034. Print 2023 Oct 26.
Pain and itch share similar neuronal networks; hence, it is difficult to explain why opioids can relieve pain but provoke itching. The present human volunteer study aimed to investigate the similarities and differences in responses to experimentally provoked pain and itching to explore the underlying fundamental mechanisms.
Twenty-four healthy volunteers were enrolled in this single-center, randomized, double-blind, placebo-controlled, parallel-group trial. Three volar forearms and two mandibular areas were marked, and participants randomly received morphine (20 mg) or identical placebo tablets. Heat, cold, and pressure pain thresholds, and vasomotor responses were assessed at baseline and after oral morphine administration. Itch provocations were induced by intradermal application of 1 % histamine or a topical cowhage (non-histaminergic itch) to a marked area of the skin. The participants were subsequently asked to rate their itching and pain intensities. The assessments were repeated for all marked areas.
Morphine caused analgesia, as assessed by the significant modulation of cold and pressure pain thresholds (p<0.05). There were no significant differences in histaminergic or non-histaminergic itch or pain intensity between the morphine and placebo groups. Superficial blood perfusion (vasomotor response) following histamine provocation was significantly increased by morphine (p<0.05) in both areas. No correlation was found between the provoked itch intensity and analgesic efficacy in any area or group.
Oral administration of morphine caused analgesia without modulating itch intensities but increased neurogenic inflammation in response to histamine, suggesting that different opioid mechanisms in histaminergic and non-histaminergic neurons evoke neurogenic inflammation.
疼痛和瘙痒共享相似的神经元网络；因此，很难解释为什么阿片类药物可以缓解疼痛但会引起瘙痒。本项人体志愿者研究旨在通过研究实验性诱发的疼痛和瘙痒的反应来探讨其相似性和差异性，以探索潜在的基本机制。
24 名健康志愿者参与了这项单中心、随机、双盲、安慰剂对照、平行组试验。标记三个掌心前区和两个下颌区域，参与者随机接受吗啡（20mg）或相同的安慰剂片。在口服吗啡给药前和给药后评估热觉、冷觉和压痛觉阈值以及血管运动反应。通过皮内注射 1%组织胺或局部涂牛痘（非组胺能性瘙痒）于标记皮肤区域来诱发瘙痒。随后，参与者被要求对瘙痒和疼痛强度进行评分。对所有标记区域重复进行评估。
吗啡引起镇痛作用，表现为冷觉和压痛觉阈值的显著调制（p<0.05）。在组胺能性或非组胺能性瘙痒或疼痛强度方面，吗啡组和安慰剂组之间没有显著差异。组胺刺激后，两种区域的表皮血液灌注（血管运动反应）均显著增加（p<0.05）。在任何区域或组中，诱发瘙痒强度与镇痛效果之间均未发现相关性。
口服吗啡引起镇痛作用而不调制瘙痒强度，但增加了组胺引起的神经源性炎症，提示组胺能性和非组胺能性神经元中的不同阿片类药物机制引起神经源性炎症。
