Analgesic Effect of Oxytocin Receptor Modulation in Healthy Volunteers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Change in intramuscular electrical pain threshold compared to baseline
研究概览
简要总结
Carbetocin is a synthetic analogue of the hormone Oxytocin and is routinely used in obstetric anesthesiology to control uterine bleeding after cesarean section. As an incidental finding, women who received carbetocin had less pain after cesarean section than women who had received Oxytocin. Carbetocin may therefore have an analgesic effect.
The present study examines this analgesic effect using different sensory tests, e.g. pressure, heat, cold and electrical pain before and after administration of carbetocin in healthy male volunteers. Any changes in these sensory tests might be indicative of an analgesic property of carbetocin.
详细描述
Background
Chronic pain is still a largely unresolved issue, causing suffering, disability and high social costs. The search for novel pharmacological targets is therefore a priority. A recent study on postpartal bleeding came to the accidental finding of a possible analgesic action of the oxytocin agonists carbetocin.
Oxytocin is a well known nonapeptide synthesized in the hypothalamus, acting as neurohormone during parturition and the milk ejection reflex. Animal studies have found that descending pathways for oxytocin synthetizing neurons project to the lamina I-II of the spinal cord, where they activate a subpopulation of glutamatergic and GABAergic interneurons. In addition to GABAergic hyperpolarisation, models of oxytocin selectively blocking A-delta and C-fibers have been published. Intrathecal administration of oxytocin prevents long-term potentiation in the dorsal horn, which is thought to be an important mechanism of enhanced central pain processing.
Antagonism to GABAergic and glycinergic neurotransmission mimics many symptoms of inflammatory and neuropathic pain. A loss of synaptic inhibition in the dorsal horn occurs in animal models of experimental pain.
Inhibitory synaptic transmission in the spinal cord dorsal horn use GABA and glycine as their principal fast neurotransmitters. Both of them open the Cl- -channels, which induce postsynaptic hyperpolarisation and impairs the propagation of excitatory potentials on dendrites of neurons. Immunofluorescence studies have revealed abundant glycinergic innervations in the dorsal horn. According to this model, inhibitory GABAergic and glycinergic interneurons in the superficial spinal dorsal horn are key components in the control of pain transmission from the periphery to the brain. The model states that a non-painful stimulation is felt as non painful as long as the synaptic GABAergic and glycinergic inhibition remains intact. A human study on GABAergic modulation of pain by benzodiazepines has been recently performed by our group and was suggestive for an analgesic action. However, these drugs cause sedation and addiction, which strongly limit their clinical usefulness. A pharmacological GABA modulation via the oxytocin receptor may be an attractive alternative, since oxytocin agonists are devoid of these side effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •pain-free
- •written informed consent
- •Exclusion Criteria
- •chronic pain
- •acute pain at time of testing
- •sign or suspicion of neurological dysfunction at the tested sites
- •intake of opioids
- •intake of benzodiazepines
- •intake of antidepressants
- •intake of anticonvulsants
- •intake of any analgesic drug 48h prior to test
- •known allergy to carbetocin
- •allergy to capsaicin
- •cardiovascular disease
- •asthma bronchiale
- •history of liver disease
- •history of renal disease
排除标准
- 未提供
研究组 & 干预措施
Carbetocin first
Subjects receive carbetocin 0.1 mg intravenously in the first session and placebo (NaCl 0.9%) in the second session
干预措施: Carbetocin (Drug)
Carbetocin first
Subjects receive carbetocin 0.1 mg intravenously in the first session and placebo (NaCl 0.9%) in the second session
干预措施: Placebo (Drug)
Placebo first
Subjects receive placebo (NaCl 0.9%) intravenously in the first session and carbetocin 0.1 mg in the second session
干预措施: Carbetocin (Drug)
Placebo first
Subjects receive placebo (NaCl 0.9%) intravenously in the first session and carbetocin 0.1 mg in the second session
干预措施: Placebo (Drug)
结局指标
主要结局
Change in intramuscular electrical pain threshold compared to baseline
时间窗: 10, 60 and 120 minutes after carbeoticin administration
次要结局
- Capsaicin-induced area of hyperalgesia and allodynia(10, 60 and 120 minutes after carbeoticin administration)
- Single intramuscular electrical pain threshold(10, 60 and 120 minutes after carbeoticin administration)
- Heat pain detection threshold(10, 60 and 120 minutes after carbeoticin administration)
- Single cutaneous electrical pain thresholds(10, 60 and 120 minutes after carbeoticin administration)
- Repeated cutaneous electrical pain thresholds(10, 60 and 120 minutes after carbeoticin administration)
- Nociceptive withdrawal reflex thresholds of the foot(10, 60 and 120 minutes after carbeoticin administration)
- Heat pain tolerance threshold(10, 60 and 120 minutes after carbetocin administration)