Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The goal of this study was to assess the effects of the dorsal root entry zone (DREZ) lesioning procedure, microsurgical DREZ-otomy (MDT), on spinal cord somatosensory function based on peri- and intraoperative clinical and electrophysiological data. The study was performed prospectively on a series of 20 patients suffering from either chronic neurogenic pain or spasticity. Physiological observations were made of the intraoperative evoked electrospinographic recordings as collected from the surface of the spinal cord. The MDT procedure produced analgesia or severe hypalgesia, moderate hypesthesia, and only slight deficits in proprioception and cutaneous spatial discrimination on the body segments operated on. These clinical data correlated well with evoked electrospinographic recordings, which showed a moderate effect of MDT on presynaptic compound action potentials recorded from the spinal cord (N11 and N21), a partial or even reversible effect on the cortical postcentral N20 wave, a more marked effect on the postsynaptic dorsal horn waves N13 and N24 related to large primary afferent fibers, and a disappearance of dorsal horn waves related to finer afferents (N2 and possibly N3). These data provide evidence for an acceptably selective action of MDT on spinal cord nociceptive mechanisms, and for a partial, often slight, involvement of the other somatosensory domains. The presence of abnormal evoked electrospinographic waves is discussed in relation to the mechanisms of neurogenic pain and spasticity. The hypothesis of a "retuning" of the dorsal horn as the mode of action of MDT is presented.
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PMID:Somatosensory function following dorsal root entry zone lesions in patients with neurogenic pain or spasticity. 203 52

Pharmacological interest in the tripeptide thyrotropin-releasing hormone (TRH) is due to the multiple effects it produces. In fact, apart from taking part in regulating the activity of the hypothalamo-pituitary-thyroid axis, TRH produces various neuropharmacological effects which indicate a biological role that is probably more important than that of a releasing hormone. Trials performed in animals have shown, for example, the dose-dependent capacity of TRH to induce analgesia, probably by interacting with the opioid peptide system. Motor activity is affected by TRH. In fact this tripeptide elicits an increase in spontaneous motor and explorative activities by interacting with the dopaminergic neurotransmitter system at the nucleus accumbens level. The neuropharmacological activities of TRH include an interesting arousal effect and an analeptic action on generalized depression of the CNS whether this depression is of natural origin, such as hibernation, or induced pharmacologically (barbiturates, ethanol) or of a traumatic origin (coma). This analeptic action is attributable to stimulation of cholinergic neurons in the septo-hippocampal area and to the presence of terminals containing TRH in the lateral septum and TRH receptors concentrated especially in the medial septum and diagonal band of Broca. It has also been suggested that TRH localized in the pineal gland has a part in activating the neuronal mechanisms of arousal. Associated with the arousal effect and especially evident in variously originated shock conditions are the activating effects of TRH on vegetative functions (body temperature, circulation, the gastrointestinal tract). These stimulatory activities on the CNS were the rationale for therapeutic use of TRH in the initial treatment of coma due to brain trauma and for the treatment of endogenous depression. A most interesting property of TRH is that of counteracting the neurological deficit due to experimental lesion of the spinal cord particularly with regard to spasticity and ataxia. Electrophysiological trials have shown that TRH depolarizes the motoneurons in frog spinal cord thereby increasing the monosynaptic reflex. Furthermore, TRH has recently been shown to have a trophic effect on cultures of rat fetus spinal cord. On this basis TRH has been used successfully for the treatment of amyotropic lateral sclerosis (Charcot's syndrome) and spinocerebellar degeneration. Further support for this therapeutic strategy is given by the demonstration that deafferentiation of rat spinal cord produces an increased density of TRH spinal receptors. Recent studies have also given encouraging results on the possible therapeutic use of TRH for the treatment of Alzheimer's disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Pharmacologic profile of protirelin tartrate]. 212 84

Postoperative pain control can be a major problem after selective dorsal rhizotomy for the treatment of spasticity. We report the use of epidural morphine delivered via a catheter placed at surgery for postoperative analgesia in 28 consecutive patients undergoing this procedure. Pain was well controlled using this technique, and no patients required concomitant parenteral analgesia. There were no instances of respiratory depression, wound infection, or central nervous system depression, and the patients were easily mobilized in the early postoperative period. Epidural morphine is concluded to be a safe and very efficacious method of analgesia after selective dorsal rhizotomy.
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PMID:Use of epidural morphine for control of postoperative pain in selective dorsal rhizotomy for spasticity. 248 50

Several opiate receptor systems have been identified in the spinal cord. They produce a powerful analgesia when opioid agonists are administered intrathecally in the intact, unanesthetized animal. These effects appear mediated by an action on opioid receptors which are located presynaptically, in the terminals of primary afferents, and postsynaptically on certain dorsal horn neurons. Based on structure-activity relationships in different tests, quantitative studies of naloxone antagonism and selective cross tolerance, it appears that, in the spinal cord, there are three distinguishable populations of opioid receptors: mu, delta and kappa. Aside from the effects on nociception, these receptors are also associated with a variety of spinal mechanisms related to other aspects of sensory, autonomic and motor functions. Though in some cases these represent important side-effects (e.g. inhibition of the micturition reflex), in others, the subtle effects may have important therapeutic benefits (e.g. relieving spasticity in spinal injured patients).
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PMID:Spinal opiates: a review of their effect on spinal function with emphasis on pain processing. 282 25

Electrical subcutaneous nerve stimulation of radial, median, and saphenous nerves has been shown to produce prolonged analgesia. In a double blind study, such stimulation also suppressed clonus for 3 hours after stimulation ceased in subjects with spasticity. Since the effect is contralateral, each subject was his own control. Because stimulation of the nerve in the wrist suppressed ankle clonus, the mechanism mediating the effect must be centrifugal inhibition. These results suggest that subcutaneous nerve stimulation may also be a tool in the management of spasticity.
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PMID:Modulation of spasticity: prolonged suppression of a spinal reflex by electrical stimulation. 706 82

Selective dorsal rhizotomy (SDR) is a neurosurgical procedure used for treating lower extremity spasticity in patients with cerebral palsy. The purpose of this paper is to present a review of our institution's first three years' experience with postoperative pain and spasticity management in patients who have undergone SDR. The medical records of the 55 patients who had an SDR during the study period were reviewed. The basis of postoperative analgesia was morphine, with the majority of patients receiving continuous morphine infusions (20-40 micrograms.kg-1.hr-1 (n = 49), 60 micrograms.kg-1.hr-1 (n = 1)). Four patients used a patient-controlled delivery system. One patient had successful analgesia with epidural morphine. Ketorolac (1 mg.kg-1 i.v. loading dose followed by 0.5 mg.kg-1 i.v. every six hr for 48 hr) was used as an adjunct to morphine in six patients. For management of postoperative muscle spasm, an intravenous benzodiazepine was used (diazepam 0.1 mg.kg-1 (n = 2), or midazolam infusion 10-30 micrograms.kg-1.hr-1 (n = 51)). All patients were cared for on a ward where nurses were familiar with the use of continuous opioid and benzodiazepine infusions. All patients received continuous cardiorespiratory monitoring as well as frequent nursing assessment. There were no episodes of postoperative apnoea or excessive sedation. We have found the use of continuous infusions of morphine and midazolam, along with adjunct ketorolac, to be effective in treating postoperative pain and muscle spasms following SDR.
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PMID:Pain management for children following selective dorsal rhizotomy. 806 89

Spasticity and pain are common disabling sequelae following spinal cord injury (SCI) and are often difficult to manage. The two problems are also not infrequently related. A variety of pharmacological and other approaches have been described for management of these problems in SCI. This case study reports a 32-year-old woman with an established incomplete C5 tetraplegia (anterior cord syndrome) who developed severe, intractable anal spasm following a hemorrhoidectomy, which persisted despite very good healing. This prevented evacuation of her bowels and resulted in severe rectal pain and episodes of autonomic dysreflexia. Attempts to modify the rate and mode of delivery of intrathecal baclofen through an existing programmable infusion pump failed to reduce anal sphincter spasm or improve symptoms. A right-sided pudendal block with lignocaine provided some relief. Clonidine was added to baclofen in the pump reservoir and both drugs were administered intrathecally in combination. This resulted in an immediate improvement in anal sphincter spasm and pain relief, allowing rapid reestablishment of her normal bowel pattern without need for any supplemental analgesia. It appears that intrathecal clonidine may have an important role in the treatment of spasticity, either as a single or an adjuvant agent, when intrathecal baclofen alone is ineffective or there is increasing tolerance to baclofen. Intrathecal clonidine may also prove useful in the management of intractable neuropathic pain.
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PMID:Intrathecal clonidine and baclofen in the management of spasticity and neuropathic pain following spinal cord injury: a case study. 870 79

Incubation of highly enriched neurons from rat cerebral cortex with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 for 18 h results in fragmentation of DNA at internucleosomal linkers, a feature of apoptosis. We report that neurons respond to exposure to gp120 with an increased release of arachidonic acid via activation of phospholipase A2. This process is not inhibited by antagonists of the N-methyl-D-aspartate (NMDA) receptor channels. To investigate the influence of arachidonic acid on the sensitivity of NMDA receptor towards its against, low concentrations of NMDA were coadministered with arachidonic acid. Under these conditions the NMDA-mediated cytotoxicity was enhanced. We conclude that gp120 causes an activation of phospholipase A2, resulting in an increased release of arachidonic acid which in turn sensitizes the NMDA receptor. Two compounds were found to act cytoprotectively against the deleterious effect caused by gp120 on neurons: Memantine [1-amino-3,5-dimethyladamantane] and Flupirtine [2-amino-3-ethoxycarbonylamino-6-(4-fluoro-benzyl-amino)-pyridine maleate]. Both compounds have been found to display a potent cytoprotective effect on neurons treated with the excitatory amino acid NMDA or with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120. The NMDA antagonist Memantine, a drug currently used in the therapy of spasticity and Parkinson's disease, prevented the effects of gp120 at micromolar concentrations. Flupirtine was previously found to be a centrally acting, nonopiate analgesic agent which additionally possesses anticonvulsant and muscle-relaxant activity at doses similar to those producing analgesia. The cytoprotective effect of Flupirtine in vitro was significant (above 10 microM). Considering the fact that both Memantine and Flupirtine display almost no clinical side effects, these drugs may prove useful both in preventing primary infection of brain cells with the HIV virus, as well as in treating the neurological disorders often associated with the immunodeficiency syndrome such as AIDS-related dementia.
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PMID:Neurotoxicity in rat cortical cells caused by N-methyl-D-aspartate (NMDA) and gp120 of HIV-1: induction and pharmacological intervention. 882 91

Selective dorsal root rhizotomy is performed for relief of spasticity in children with cerebral palsy. Postoperative pain relief can be provided by intrathecal morphine administered at the time of the procedure. We sought to define an optimal dose of intrathecal morphine in children undergoing selective rhizotomy, through a randomized, double-blinded prospective trial. After institutional approval and parental written informed consent, 27 patients, ages 3-10 years, were randomized to receive 10, 20, or 30 micrograms.kg-1 (Groups A, B, and C, respectively) of preservative-free morphine administered intrathecally by the surgeon after dural closure. Postoperatively, vital signs, pulse oximetry, and pain intensity scores were recorded hourly for 24 hr. Supplemental intravenous morphine was administered postoperatively according to a predetermined schedule based on pain scores. There was considerable individual variability in the time to initial morphine dosing and cumulative supplemental morphine dose. Time to first supplemental morphine dose was not different between groups. When compared to Groups A and B, cumulative 6-hr supplemental morphine dose was significantly lower in Group C (38.6 +/- 47 micrograms versus 79.1 +/- 74 and 189.6 +/- 126 for Groups A and B, respectively). By 12 hr, cumulative supplemental morphine dose was similar in Groups A and C. Group B consistently had a higher supplemental dose requirement than Groups A and C at 6, 12, and 18 hr. By 24 hr, there was no difference in cumulative dose among groups. Postoperative pain scores and the incidence of respiratory events, nausea, vomiting and pruritus were comparable among groups. These data suggest that intrathecal morphine at 30 micrograms.kg-1 provides the most intense analgesia at 6 hr following selective dorsal root rhizotomy, but was otherwise comparable to the 10 micrograms.kg-1 dose.
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PMID:Intrathecal morphine for analgesia in children undergoing selective dorsal rhizotomy. 885 77

Considerable progress has been made in understanding and treating pain associated with pediatric AIDS. The World Health Organization (WHO) estimates that 1000 new pediatric HIV infections occur daily, with 67% in Africa and 30% in South and Southeast Asia. Perinatally infected children show two types of progression, a precocious form that is usually fatal by the 4th year and a less rapidly progressing form in which survival exceeds 80% at age 7. Neurologic effects are frequently apparent by 3-6 months in the severe form. The pain may result specifically from the HIV infection and its complications, from intercurrent or opportunistic infections, or from examinations and treatment. The emotional pain suffered by pediatric HIV patients is often very great. Seropositive children are more subject to bacterial infections than seropositive adults, and their infections are more recurrent, prolonged, and painful than those in immunocompetent children. Infants with HIV encephalopathy may suffer painful sensations from mild stimuli and extreme irritability and spasticity. Abdominal HIV pain often results from multifactorial etiologies, and the usual therapies may be of little efficacy. Children with full-blown AIDS may complain of joint or muscle pain or headaches that are of unexplained etiology. Indications for painful diagnostic procedures should be carefully considered before the child is subjected to them, and protocols for analgesia should be developed. Pain medications may be selected according to the WHO classification, in accordance with the intensity of the pain. Antidepressants and anticonvulsants may be used for neuropathic pain, and painful spasticity may be reduced with myorelaxants. Children are often responsive to behavioral methods such as relaxation, hypnosis, or distraction.
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PMID:[Pain from AIDS (child)]. 1234 7


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