Intravenous Nefopam Reduces Postherpetic Neuralgia during the Titration of Oral Medications

BACKGROUND: The recently known analgesic action mechanisms of nefopam (NFP) are similar to those of anticonvulsants and antidepressants in neuropathic pain treatment. It is difficult to prescribe high doses of oral neuropathic drugs without titration due to adverse effects. Unfortunately, there are few available intravenous analgesics for the immediate management of acute flare-ups of the chronic neuropathic pain. The aim of this study was to determine the additional analgesic effects for neuropathic pain of NFP and its adverse effects during the titration of oral medications for neuropathic pain among inpatients with postherpetic neuralgia (PHN). METHODS: Eighty inpatients with PHN were randomly divided into either the NFP or normal saline (NS) groups. Each patient received a 3-day intravenous continuous infusion of either NFP with a consecutive dose reduction of 60, 40, and 20 mg/d, or NS simultaneously while dose titrations of oral medications for neuropathic pain gradually increased every 3 days. The efficacy of additional NFP was evaluated by using the neuropathic pain symptom inventory (NPSI) score for 12 days. Adverse effects were also recorded. RESULTS: The median NPSI score was significantly lower in the NFP group from days 1 to 6 of hospitalization. The representative alleviating symptoms of pain after using NFP were both spontaneous and evoked neuropathic pain. Reported common adverse effects were nausea, dizziness, and somnolence, in order of frequency. CONCLUSIONS: An intravenous continuous infusion of NFP reduces spontaneous and evoked neuropathic pain with tolerable adverse effects during the titration of oral medications in inpatients with PHN.

The Effects of Intrathecal Bupivacaine and Bupivacaine Dextrose on Neurologic Injury and NMDA Receptor mRNA Expression in Transient Spinal Ischemia in the Rat / 대한마취과학회지

BACKGROUND: Spinal cord injury occurring as a result of surgical repair of thoracic and thoracoabdominal aortic disease remains a devastating complication. Excitatory amino acids have been known to cause neurologic injury after neuronal ischemia. The purpose of this study was to elucidate the effects of intrathecal bupivacaine or bupivacaine dextrose on neurologic outcome and to characterize NMDA receptor gene expression in transient spinal ischemia. METHODS: Rats were anesthetized with isoflurane, divided by 3 groups: Control (C group), Intrathecal 0.5% bupivacaine 40 microliter (B group) and Intrathecal 0.5% bupivacaine with 8.5% dextrose 40 microliter (D group). Spinal ischemia was produced by induced hypotension and thoracic aortic cross clamping. After spinal ischemia, neurologic scores were assessed at 1, 2, 3, 24, and 48 hours. After 3 hours rats (Sham, C, B, and D groups) were euthenized and spinal cords and cerebral cortexes were removed for to assay NMDAR mRNA. 48 hours after ischemia, rats (C and B groups) were euthenized and spinal cords were removed for histologic examination. RESULTS: The neurologic scores of B group were significantly lower than those of C group or D group. Rats of D group showed seizure 1 hour after ischemia and died about 3 hours after ischemia. There were no significant changes in the NMDAR mRNA expressions of the cerebral cortex and the spinal cord. C group showed more significant apoptosis by TUNEL staining than B group. CONCLUSIONS: Intrathecal bupivacaine, not bupivacaine dextrose, proved effective at preventing neurologic injury after transient spinal ischemia. Intrathecal dextrose might be involved in the induction of generalized tonic-clonic seizure after spinal ischemia.

The Effects of Intravenous Ketamine on Neurologic Injury and Glutamate Receptor Gene Expression after Transient Spinal schemia in the Rat / 대한마취과학회지

BACKGROUND: Massive release of glutamate plays an important role in ischemic neuronal injury, and modification of this process may provide neuroprotection. We studied the protective effects of the N- methyl-D-aspartate receptor antagonist ketamine on hind limb motor function and glutamate receptor of gene expression in an experimental model of spinal cord ischemia. METHODS: Transient spinal cord ischemia was induced by 15 min of thoracic aortic occlusion in 24 anesthetized Sprague-Dawly rats. Rats were randomly assigned to one of three treatment groups (n = 8 each): C group, no intervention; K30 group, ketamine 30 mg/kg intravenously; or K50 group, ketamine 50 mg/kg intravenously. Normothermia (38degreesC) was maintained during ischemia. After spinal ischemia neurologic function was evaluated immediately and after 1, 2 and 3 hours. After 3 hours rats were euthanized and spinal cords were removed for the assay of NMDAR and mGluR5 mRNA. RESULTS: Neurologic outcome was better in the K30 group than the C or K50 group (P < 0.05). The NMDAR mRNA expression of the K30 and K50 group were greater than those of the C group. The mGluR5 mRNA expression increased after spinal ischemia. There were no differences between groups. CONCLUSIONS: In this study demonstrated that treatment with ketamine 30 mg/kg intravenously before ischemia increases tolerance of spinal cord motor neurons in a period of normothermic ischemia.