The anti-inflammatory effect of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with inhibition of cyclooxygenase (COX), the rate-limiting enzyme responsible for the synthesis of prostaglandins. Since oxygen free radicals can act as second cellular messengers, especially to modulate the metabolism of arachidonic acid and the prostaglandin tract, it seems plausible that antioxidants might affect the production of prostaglandin by activated cells. This research is focused on the effect of the antioxidant N-acetylcysteine (NAC) on the inhibition of prostaglandin E(2) formation in activated monocytes by specific and non-specific COX inhibitors. We found that lipopolysaccharide-induced prostaglandin E(2) formation was significantly reduced by rofecoxib and by diclofenac, two NSAIDs. Addition of NAC to each of these drugs enhanced the effect of the NSAIDs. These results suggest that one might expect either a potentiation of the anti-inflammatory effect of COX inhibitors by their simultaneous administration with NAC, or obtaining the same anti-inflammatory at lower drug levels.
An open trial was conducted to study the potential efficacy of the antiepileptic agent lamotrigine in relieving the sciatic pain and the relationship between lamotrigine dosage, plasma concentration and the clinical response. Subsequent to a 1 week washout period from previous analgesics, lamotrigine dose was titrated on a weekly basis from 25 to 400mg/day and was maintained at that dose for additional 4 weeks. Spontaneous pain, the Short Form McGill Pain Questionnaire (SFMPQ), the Straight Leg Raise (SLR) test, and range of motion of the lumbar spine (leaning foreword, to the affected side) were used to assess lamotrigine efficacy. Lamotrigine plasma concentration was tested at the end of each week during the titration period and at the end of the study. Fourteen patients were enrolled in the study. All outcome measurers improved compared to baseline during the titration period, but reached a statistically significant level of improvement only at the 400mg dose. A linear correlation was found between mean lamotrigine dose, mean plasma concentration and mean weekly spontaneous pain, mean SLR and mean bending the affected side, but not with the SFMPQ score. Study results suggest lamotrigine is a potentially effective and safe compound for the treatment of painful lumbar radiculopathy, and that it is likely to act in a dose- and plasma concentration-dependent fashion.
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