BACKGROUND: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. METHODS: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. RESULTS: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. CONCLUSIONS: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.
Analgesia ; Animals ; Dopamine ; Microdialysis ; Nefopam* ; Pain Measurement ; Rats* ; Spinal Cord ; Spinal Cord Dorsal Horn ; Sulpiride ; Synaptic Transmission

BACKGROUND: Medical treatments such as restriction of phosphate, phosphate binder use, and active vitamine D therapy have been widely used for hyperparathyroidism in ESRD patients, and surgical parathyroidectomy should be considered in patients with uncontrolled hyperparathyroidism. METHODS: A retrospective study was performed in 24 ESRD patients with severe and uncontrolled hyperparathyroidism despite of medical treatment who undertook surgical parathyroidectomy in Severance hospital from 1990 to 1999. RESULTS: Sixteen patients had total parathyroidectomy with immediate autotransplant, 7 patients had subtotal parathyroidectomy and only 1 patient had minimally invasive parathyroidectomy. An excellent short-term control of hyperparathyroidism was achieved in all patients after parathyroidectomy. Preoperative bone and joint pain improved in 16 of 19 patients. Muscle weakness and pain improved in 11 of 17 patiens, malaise improved in 8 of 10 patients and pruritus improved in 10 of 13 patients. In addition, clinical laboratory finding improved after parathyroidectomy. No clinical differences were seen between 16 patients who undertook total parathyroidectomy with immediate autotransplant and 7 patients who undertook subtotal parathyroidectomy. Recurrence of hyperparathyroidism ocurred in 5 of 24 patients with 4 nodular hyperplasia and 1 diffuse hyperplasia in pathologic finding. The less degree of attenuated response of intact PTH levels immediately after operation was observed in 5 recurrent cases. CONCLUSION: Good results were obtained after parathyroidectomy. We believe that histologic subtype and the attenuated response of intact PTH after surgical parathyroidectomy could be possible predictors of the recurrent hyperparathyroidism.
Arthralgia ; Autografts ; Humans ; Hyperparathyroidism* ; Hyperparathyroidism, Secondary ; Hyperplasia ; Kidney Failure, Chronic* ; Muscle Weakness ; Parathyroidectomy* ; Pruritus ; Recurrence ; Retrospective Studies ; Vitamins