The study design will be prospective, randomized, double-blind, parallel groups, placebo-controlled clinical trial. A detailed informed consent will be signed by the eligible participants before recruitment and randomization. Randomization will be done by using computer-generated random numbers that will be placed in separate opaque envelopes that will be opened by study investigators just before IT block. The syringes used will be labeled as A and B per their content. The identical coded syringe will be prepared by trained anesthesia technicians who will not be included in the study.
|Published (Last):||17 January 2014|
|PDF File Size:||1.31 Mb|
|ePub File Size:||10.1 Mb|
|Price:||Free* [*Free Regsitration Required]|
Top THREE characteristics of chronic pain result in failure of therapy and have promoted considerable fundamental research into their mechanism s and treatments. First is the development of altered responses to sensory stimuli - exaggerated pain to a painful stimulus hyperalgesia and pain to a normally nonpainful stimulus allodynia.
Allodynia to light touch is a common and distressing complaint in many patients with chronic pain and is considered a characteristic of neuropathic pain. Second is the reliance of pain and allodynia in many patients on activity of the sympathetic nervous system, because sympathetic blockade often leads to pain relief. Our initial results of increased potency of intrathecally injected neostigmine and its combination with clonidine in this model led us to further examine the sympathetic nervous system dependency of this model, using chemical and surgical sympatholytic approaches.
After surgery, the animals were housed individually with free access to food and water and allowed to recover for at least 1 week before study. The first 14 rats were anesthetized at least 2 weeks later with halothane, and an intrathecal catheter PE tubing was inserted through a small hole in the cisterna magnum and advanced caudad 8 cm such that the tip lay in the intrathecal space around the lumbar enlargement. Experiments were performed in these animals between 1 and 2 weeks after implantation of the intrathecal catheter.
The second 11 rats were anesthetized with halothane at least 2 weeks after spinal nerve ligation surgery, and a PE catheter was inserted in the jugular vein. At least 2 days after experiments with phentolamine and guanethidine described later , these rats were anesthetized with halothane, and a surgical sympathectomy was performed as previously described. Experiments were performed in these animals on the day after surgery and again 1 week later.
Withdrawal Threshold Testing Rats were placed in individual plastic cages on a plastic mesh bottom floor, which permitted access to their hind paw. After accommodation to the cage, mechanical threshold was assessed by application of standard von Frey filaments Stoelting, Wood Dale, IL. Each filament was applied perpendicularly to the paw for 5 - 6 s. Brisk withdrawal or paw flinching were considered as positive responses, in which case the next filament tested was the next lower force.
In the absence of such responses, the next filament tested was the next greater force. Withdrawal threshold was calculated as described by Chaplan et al. Experimental Groups First, the effect of neostigmine and clonidine were determined. Combination studies also were performed to test the hypothesis that neostigmine might counteract the effect of clonidine on reduction in allodynia, because these agents have opposing actions on activity of the sympathetic nervous system.
Experiments were separated by a minimum of 3 days. Next, the effects of sympatholytic treatments were determined in separate animals. Experiments were separated by a minimum of 4 days. These rats then underwent surgical sympathectomy, and withdrawal thresholds were tested and 1 and 7 days after surgery.
The acute effects of intravenously administered phentolamine and guanethidine on arterial blood pressure was determined in a separate group of lightly anesthetized rats without spinal nerve ligation surgery.
Drugs Intrathecal injections were performed in a 5-[micro sign]l volume followed by a [micro sign]l flush with saline, and intravenous injections were performed in a 0. All drugs were dissolved in saline for injection. Guanethidine monosulfate, neostigmine bromide, and phentolamine hydrochloride were obtained from Sigma Chemical Co. Louis, MO. Effect of drug or surgical treatment was determined by a nonparametric one-way repeated-measures analysis of variance. Isobolographic analysis was performed as previously described.
Results Paw withdrawal threshold decreased from a median of Intrathecal injection of saline did not affect withdrawal threshold in rats after spinal nerve ligation Figure 1. Intrathecally administered clonidine produced a dose-dependent increase in withdrawal threshold after spinal nerve ligation surgery, returning withdrawal threshold to presurgery levels at a cumulative dose of 30 - 45 [micro sign]g Figure 2 , bottom.
Withdrawal threshold to stimulation by von Frey filaments before surgery Baseline , after spinal nerve ligation SNL , and for 60 min after intrathecal injection of saline in SNL-treated rats. There was no significant effect over time in the saline-treated animals.
Withdrawal threshold to stimulation by von Frey filaments before surgery Base , after spinal nerve ligation SNL , and for 60 min after cumulative intrathecal injection of neostigmine top or clonidine bottom.
Analgesic effect of intrathecal neostigmine combined with bupivacaine and fentanyl.
Shakarn Because magnesium is a noncompetitive antagonist to NMDA receptors, it has the potential to prevent central sensitization from peripheral nociceptive stimulation. Although solutions containing preservatives should not be injected IT, methyl- and propyl-paraben have not been demonstrated to be toxic. Blood pressure or intrwthecal rate before intrathecal injection or after bupivacaine injection did not differ in the groups Figure 1. Open in a separate window. Ann R Coll Surg Engl.
Intrathecal Neostigmine for Prevention of PDPH
Afr J Med Med Sci. Analgesic effect of intrathecal neostigmine combined with bupivacaine and fentanyl. The search for ideal additives to local anaesthetic agents to prolong the analgesic effects poses a challenge to the anaesthetists. Neostigmine, an anticholinesterase, presents a novel approach to providing analgesia. Neostigmine, when given intrathecally, inhibits breakdown of an endogenous spinal neurotransmitter, acetylcholine, thereby inducing analgesia.
E-mail: moc. This article has been cited by other articles in PMC. Abstract Background and Aim: Intrathecal IT neostigmine has been used as an adjunct to spinal anesthesia. The purpose of this study was to determine whether a combination of low-dose neostigmine IT would enhance analgesia of a fixed dose of fentanyl IT, in patients undergoing unilateral total knee replacement TKR surgery with spinal anesthesia.
E-mail: ri. This article has been cited by other articles in PMC. Abstract Background: Regional anesthesia is widely used to perform different surgical procedures including those performed on the extremities. In this study, the anesthetic effects of adding intrathecal neostigmine or magnesium sulphate to bupivacaine in patients under lower extremities surgeries were assessed. Materials and Methods: In this double-blind randomized clinical trial, 90 patients, candidate for lower extremities surgeries in a training hospital, were recruited. Then sensory and motor onset and complete block and the time of recovery were measured.