mobic and Subarachnoid-Hemorrhage

In animal research, authorities require a classification of anticipated pain levels and a perioperative analgesia protocol prior to approval of the experiments. However, data on this topic is rare and so is the reported use of analgesics. We determined surrogate parameters of pain and general well-being after subarachnoid hemorrhage (SAH), as well as the potential for improvement by different systemic analgesia paradigms. Brain injury was induced by filament perforation to mimic SAH. Sham-operated mice were included as surgical control groups with either neck or no-neck preparation. Mice with controlled cortical impact (CCI) injury were included as a control group with traumatic brain injury (TBI), but without neck preparation. Mice were randomized to buprenorphine, carprofen, meloxicam, or vehicle treatment. 24 h after SAH, CCI or sham surgery, pain and stress levels were assessed with a visual assessment score and the amount of food intake was recorded.. Neck preparation, which is required to expose the surgical field for SAH induction, already increased pain/stress levels and sham surgeries for both CCI and SAH reduced food intake. Pain/stress levels were higher and food intake was lower after SAH compared with CCI. Pain/stress levels after CCI without analgesic treatment were similar to levels after SAH sham surgery. Pain treatment with buprenorphine was effective to reduce pain after SAH, whereas lower pain/stress intensity levels after CCI were not improved.. This study emphasizes the importance of pain and stress assessment after surgeries and the efficacy of buprenorphine to improve pain and comfort levels after experimental SAH.

Topics: Animals; Brain Injuries, Traumatic; Buprenorphine; Carbazoles; Eating; Male; Meloxicam; Mice; Pain Measurement; Stress, Psychological; Subarachnoid Hemorrhage

Meloxicam is a cyclo-oxygenase-2 (COX-2) preferential non-steroidal anti-inflammatory drug with very effective analgesic and anti-inflammatory effects in swine. Previous reports in piglets have demonstrated that meloxicam also inhibits COX-1 and reduces production of thromboxane significantly. We use preinjury analgesia in our immature swine (3-5-day-old piglets) model of brain injury using rapid head rotations without impact. In 23 consecutive subjects we found that premedication with meloxicam (n = 6) produced a significantly higher mortality rate (5/6 or 83%) than buprenorphine (n = 17, 1/17 or 6%, P < 0.02). On gross neuropathological examination of the meloxicam-treated swine, we observed massive subdural and subarachnoid bleeding which were not present in buprenorphine-premedicated animals. To our knowledge there are no previous reports in swine of increased bleeding or platelet inhibition associated with meloxicam administration and further research is needed to define mechanisms of action in piglets. We caution the use of meloxicam in swine when inhibition of platelet aggregation might adversely affect refinement of experimental research protocols, such as in stroke, trauma and cardiac arrest models.

Topics: Amyloid beta-Protein Precursor; Animals; Animals, Newborn; Brain; Brain Injuries; Buprenorphine; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Hematoma, Subdural; Injections, Intramuscular; Meloxicam; Premedication; Subarachnoid Hemorrhage; Survival Rate; Swine; Thiazines; Thiazoles

Cerebral vasospasm influences morbidity and mortality following subarachnoid haemorrhage (SAH). Inflammation is believed to play a role in post-haemorrhagic vasospasm. Meloxicam is a non-steroidal anti-inflammatory drug. We investigated the effect of meloxicam on a rat femoral artery vasospasm model using the radial wall thickness and cross-sectional lumen area as parameters under light, scanning and transmission electron microscopy examination. Rats were randomly separated into SAH, SAH+ meloxicam and control groups. Rats in the SAH+ meloxicam group were given meloxicam at 2 mg/kg daily for 7 days. Femoral arteries were examined by light microscopy and scanning and transmission electron microscopy, and for morphometric analysis. A statistically significant difference (p<0.001) was detected between the SAH and SAH+ meloxicam groups. Meloxicam treatment reduced ultrastructural and morphometric vasospastic changes. These findings support the hypothesis that inflammation may play a role in the pathophysiologyical pathways of post-haemorrhagic cerebral vasospasm.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Femoral Artery; Meloxicam; Random Allocation; Rats; Rats, Sprague-Dawley; Subarachnoid Hemorrhage; Thiazines; Thiazoles; Vasospasm, Intracranial