sulprostone and Pain

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Acetaminophen; Dinoprostone; Double-Blind Method; Drug Interactions; Female; Humans; Male; Mifepristone; Pain; Pregnancy

The most common preclinical models of neuropathic pain involve surgical ligation of sensory nerves, which is especially difficult in mice. Transient models of chemically sensitized allodynia are potentially useful for rapidly characterizing the analgesic profile of compounds and conducting mechanistic studies.. Increasing doses of NMDA, sulprostone (an EP1/EP3 prostaglandin receptor agonist) or phenylephrine (an alpha (1) adrenoceptor agonist) were injected intrathecally (i.t.) or i.p., and animals were subsequently assessed for allodynia. The effects of receptor antagonists and analgesic compounds on allodynia were also assessed.. A comparison of total body doses that cause allodynia following spinal or systemic administration indicated that NMDA induces allodynia in the spinal cord while sulprostone and phenylephrine act through a peripheral mechanism. Inhibition of the allodynia with receptor antagonists indicated that each agent induces allodynia by a distinct mechanism. The three models were benchmarked using compounds known to be active in neuropathic pain patients and nerve injury animal models, including gabapentin, amitriptyline and clonidine.. These transient allodynia models are a useful addition to the toolbox of preclinical pain models. They are simple, rapid and reproducible, and will be especially useful for characterizing the pain phenotype of knockout mice.

Topics: Adrenergic alpha-Antagonists; Amines; Amitriptyline; Analgesics; Animals; Clonidine; Cyclohexanecarboxylic Acids; Dinoprostone; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Excitatory Amino Acid Antagonists; Gabapentin; gamma-Aminobutyric Acid; Hyperalgesia; Injections, Intraperitoneal; Injections, Spinal; Male; Memantine; Mice; Mice, Inbred C57BL; Morphine; N-Methylaspartate; Pain; Peripheral Nervous System; Phenylephrine; Piperazines; Prostaglandin Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-1; Receptors, N-Methyl-D-Aspartate; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP1 Subtype; Reproducibility of Results; Spinal Cord; Spinal Nerves; Time Factors

Thirty-two pregnancies (11 primi- and 21 multi-gravid) with an abnormal fetus were terminated between 16 and 35 weeks (mean 22 weeks; median 20 weeks) and a continuous intravenous infusion of 1 microgram of the prostaglandin analogue sulprostone. All pregnancies were terminated vaginally, 31 of them with this regimen in a median induction-expulsion interval of 23 h (range 8-52 h). Complete expulsion of the placenta occurred in 72 per cent of cases. Median blood loss was 100 ml (range 20-2000 ml). There were only a few side-effects. We conclude that this induction regimen is both appropriate and safe for pregnancy termination in cases of fetal anomaly.. In the Netherlands, physicians did a controlled trial at the University Hospital Leiden to determine whether administration of a prostaglandin analogue at low-doses could successfully terminate 2nd and 3rd trimester pregnancies of an abnormal fetus (16-35 weeks gestation). Fetal blood sampling, amniocentesis, or ultrasound revealed an abnormal fetus in 32 women. The most frequent fetal anomaly was a chromosomal abnormality. Some other anomalies were anencephaly and multiple malformations. 11 primigravidae and 21 multigravidae received iv infusion of 0.5 mg sulprostone/minute for 60 minutes then 1 mcg sulprostone/minute until the fetus was expelled. 31 women experienced vaginal termination with a median induction-expulsion interval of 23 hours. Endocervical administration of 0.5 mg PGE2 followed by infusion of up to 2 mcg sulprostone/minute caused vaginal delivery 74 hours after treatment in the other woman who was carrying a fetus with trisomy 18. 84% of the women delivered within 36 hours. Induction-expulsion intervals were not associated with gestational age. The physicians had to manually remove the placenta in just 28% of the cases. Median blood loss stood at 100 ml. 9% of the women lost more than 1000 ml of blood but no one needed a blood transfusion. 6 women did not take pain killers. Just 6 women experienced gastrointestinal side effects and they occurred just 1 once. These results showed that administration of sulprostone at low doses is safe and appropriate as a method to terminate pregnancies with fetal anomalies. The physicians considered it even preferable to other regimens they had used in the past.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Therapeutic; Analgesia, Epidural; Dinoprostone; Female; Fetus; Humans; Infusions, Intravenous; Meperidine; Pain; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Pregnancy, Multiple; Prenatal Diagnosis

Topics: 16,16-Dimethylprostaglandin E2; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Dinoprostone; Drug Evaluation; Female; Humans; Injections, Intramuscular; Pain; Pregnancy; Prostaglandins E, Synthetic; Self Administration; Suppositories; Vagina