Analgesic effects of topical ketamine.

Topical analgesics may play an important role in the management of chronic pain and have good tolerability. Systemic ketamine has limited usage as an anesthetic and along with its potential for addiction and dependence has not gained popularity as an analgesic compound. Topical ketamine however, is devoid of serious side effects, and thus can be used in the management of various pain states such as neuropathic pain and complex regional pain syndrome. Despite using high concentrations of topical ketamine, clinically significant side effects are rare. The measured plasma levels of ketamine and norketamine in various studies were mostly below the threshold of detection. Topical ketamine has been used as compounded formulations alone in concentrations from 0.5% to 20% or in combination with other (co-)analgesics. Its efficacy may depend on the choice of vehicle, the concentration and the pain state. Suboptimal concentration of ketamine and suboptimal pharmaceutical properties of the cream base might have contributed to the negative results of some studies. In this article we will review clinical studies involving the use of topical ketamine for pain.

Comparison of intrathecal administration of urokinase and tissue plasminogen activator on subarachnoid clot and chronic vasospasm in a primate model.

Safety and efficacy of the thrombolytic agent urokinase (URO) in the elimination of subarachnoid clot and prevention of chronic vasospasm was compared with tissue-type plasminogen activator (rt-PA) in a blind, randomized placebo-controlled trial. Twenty monkeys were randomly assigned to one of five groups of four. Each group underwent baseline cerebral angiography followed by bilateral craniectomy and experimental subarachnoid hemorrhage. An Ommaya reservoir was inserted on the right side with its catheter placed into the ipsilateral subarachnoid space. Twenty-four hours later, depending upon group assignment, the animals received 100,000 IU URO, 200,000 IU URO, 1 mg rt-PA, 2 mg rt-PA, or the equivalent volume of normal saline (control group). On Day 7, angiography was repeated and the animals were killed. One animal died as a result of complications during the baseline angiography, presumably due to blood loss and prolonged anesthesia, and a replacement animal was obtained. No animals demonstrated any delayed neurological deficits. The study demonstrated that a single intracisternal bolus injection of rt-PA, 2.0 mg in 2 ml sterile water, or URO, 200,000 IU in 2 ml sterile water, 24 hours after induction of experimental subarachnoid hemorrhage in primates, was equally effective in thrombolysing ipsilateral clot, but neither dosage prevented angiographic vasospasm. Vasospasm occurred bilaterally in all groups. Whereas gross subarachnoid clot was found bilaterally in all animals in the placebo group and both smaller-dose URO and rt-PA groups, right-sided subarachnoid clot was virtually absent and left-sided clot reduced in both higher-dose URO and rt-PA groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Procollagen types I and III and transforming growth factor-beta gene expression in the arterial wall after exposure to periarterial blood.

The stiffening and thickening of the arterial wall after subarachnoid hemorrhage may reflect increased connective tissue. The purpose of this study was to examine the nature of collagen synthesis in response to periarterial blood. Rat femoral arteries were exposed to periarterial blood for varying lengths of time (control, 1, 3, 7, and 14 d). Dot-blot analysis of total ribonucleic acid extracted from the arteries (n = 10 to 15 animals each) demonstrated that the expression of procollagen Types I and III messenger ribonucleic acid increased at 7 (threefold) and 14 days. The expression of transforming growth factor-beta (TGF-beta), an important regulator of collagen synthesis, was markedly increased by 3 days (threefold), followed by a gradual decline. There were marked differences in procollagen Types I and III and TGF-beta gene expression between arteries exposed to blood and sham-operated arteries for a period of 7 days (n = 25 animals). Northern blot analysis of total ribonucleic acid extracted from cultured vascular smooth muscle cells showed that the treatment with a higher concentration of serum for 48 hours increased the expression of procollagen Types I and III and TGF-beta, whereas exposure to oxyhemoglobin did not. After exposure to periarterial blood, arterial walls show increased synthesis of procollagen Types I and III, perhaps a response to the increased secretion of TGF-beta, which in turn could be the result of exposure to serum factors.