Neither nefopam nor acetaminophen can be used as postoperative analgesics in a rat model of ischemic stroke

• Published in: Fundamental & clinical pharmacology 2017-04, Vol.31 (2), p.194-200
• Main Authors: Pétrault, Maud, Gautier, Sophie, Bérézowski, Vincent, Ouk, Thavarak, Bastide, Michèle, Pétrault, Olivier, Bordet, Régis
• Format: Article
• Language: English
• Subjects: Acetaminophen; Acetaminophen - administration & dosage; Acetaminophen - pharmacology; Analgesia; Analgesics; Analgesics, Non-Narcotic - administration & dosage; Analgesics, Non-Narcotic - pharmacology; Animal models; Animals; brain ischemia; Brain Ischemia - prevention & control; Cerebral blood flow; Disease Models, Animal; Dizocilpine Maleate - pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Drugs; Infarction, Middle Cerebral Artery; Ischemia; Male; Nefopam - administration & dosage; Nefopam - pharmacology; Neuroprotection; Neuroprotective agents; Neuroprotective Agents - pharmacology; Occlusion; Opioids; Pain; Pain perception; Pain, Postoperative - drug therapy; Pharmacology; Phase transitions; Rats; Rats, Wistar; Rodents; Stroke; Stroke - prevention & control; Surgery; Surgical Procedures, Operative - methods
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/fcp.12246

Analgesics such as opioid agonists are usually not given during the postoperative phase of experimental stroke because they are susceptible to interfere with the evaluation of neuroprotective therapies. Here, we investigate the potential of acetaminophen and nefopam, two nonopioid analgesic drugs, to exert an analgesic effect without inducing neuroprotection in a murine model of ischemic stroke. We demonstrate that acetaminophen (200 mg/kg, PO) induces a significant decrease in the infarct volume, particularly in the cortex (VEHICLE: 200.1 mm3 vs. ACETAMINOPHEN: 140.9 mm3, P < 0.05), while nefopam (2, 20 or 40 mg/kg, IM), administered at the end of middle cerebral artery occlusion (MCAO), do not influence the infarct size (VEHICLE: 268.6 mm3 vs. NEFOPAM 2: 248.8 mm3, NEFOPAM 20: 250.6 mm3 and NEFOPAM 40: 215.9 mm3, P > 0.05). Moreover, we find that nefopam administration (20 mg/kg, IM) in the acute postoperative phase do not change the level of neuroprotection induced by MK801 (3 mg/kg, IV), a well‐known neuroprotectant (VEHICLE: 268.6 mm3 vs. MK801: 194.4 mm3 and vs. MK801 + NEFOPAM 20: 195.2 mm3). On the other hand, although nefopam induces analgesia in healthy animals, it is not the case when administered during MCAO (behavior scores at 5 min: HEALTHY: 2.1 vs. HEALTHY + NEFOPAM 20: 0.6, P < 0.5; IR: 0.40 vs. IR + NEFOPAM 20: 0.67, P > 0.05). Our data suggest that neither acetaminophen nor nefopam can be used as analgesic agents to meet the needs of limiting rodent pain and distress during experimental stroke surgery.