The first two authors contributed equally to this work Atorvastatin is an HMG-CoA reductase inhibitor used to treat hypercholesterolemic conditions associated with hypertension. This study aims to investigate the anti-inflammatory and neuroprotective effects of atorvastatin on peripheral neuropathic pain. Peripheral neuropathic pain was induced by chronic constriction injury (CCI) in Sprague-Dawley rats. Rats were divided into 3 groups including shamoperated, CCI, and atorvastatin-treated. Atorvastatin (10 mg/kg) or phosphate-buffered saline was orally administered for 2 weeks. All animals were assessed by neurobehavioral tests before surgery and at days 3,7,14 after surgery. Inflammatory and neuroprotective factors were evaluated by Western blot analysis. eNOS, COX2 and iNOS in the sciatic nerve were also studied using immunohistochemistry. Atorvastatin attenuated CCI-induced nociceptive sensitization and thermal hyperalgesia in a time-dependent manner. Atorvastatin improved CCI-induced neurobehavioral/inflammatory activity by inhibition of TGF-p, pIKB/lKB, NFKB, COX2, iNOS, EP1 and EP4 in the sciatic nerve. Atorvastatin was also found to increase neuroprotection factors pAktlAkt, eNOS and VEGF. Taken together, these data indicate that atorvastatin could protect the sciatic nerve against CCI-induced neuroinflammation and nociception.Neuropathic pain, largely resulting from primary lesions in the peripheral nerve or from malfunctions in the central nervous system (CNS), has an extremely negative impact on the quality of life of patients affected by this condition (1).Studies using the chronic constriction injury (CCI) model of peripheral nerve injury have provided a deeper understanding of nociception and the events contributing to the pathogenesis of chronic pain conditions (2). Inflammatory states within the
Although epidural anesthesia is a common practice in neuraxial blockade, difficult access to the epidural space is a frequent problem in operating theaters. We designed this study of epidural blocks to determine if the spinal landmark grading system is valuable in predicting a difficult epidural block. Before the epidural block, we collected the following data: demographics, body habitus (normal, thin, obese, pregnant), spinal anatomy (normal, deformed), spinal level (lumbar, thoracic), and spinal landmark grade (grade 1: spinous processes visible; grade 2: spinous processes not seen but easily palpated; grade 3: spinous processes not seen and not palpated but the interval between them is palpated as a low landmark under the thumb; grade 4: other). We performed all 848 epidural blocks initially using a midline approach and an 18-gauge Touhy needle. We evaluated the technical difficulty of the epidural block using three methods: whether the epidural block was accomplished at the spinal level (first-level success); the total number of attempts at skin puncture (attempts-S); and total number of attempts to change ligament puncture direction (attempts-L) required to complete the epidural block. Of all examined factors, spinal landmark grade correlated best with technical difficulty as measured by all three methods. Deformed spinal anatomy and body habitus both correlated with difficulty, merely from the total numbers of attempts (attempts-S and attempts-L). Thoracic epidurals were more difficult than lumbar epidurals by all three measures of difficulty. We concluded that this spinal landmark grading system is valuable in predicting a difficult epidural block and advocate its use as a predictor by anesthesiologists.
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