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 theoretical goal of the ideal drug - to localize specifically and directly to its intended target, have a high therapeutic index and achieve therapeutic efficacy without side effects - is becoming feasible through improved drug delivery and targeting. The clinical advantages of improved drug delivery include continuously therapeutic drug levels, decreased drug dose, improved patient compliance, increased viability of short-lived pharmaceuticals like peptides and proteins, less invasive routes of administration, reduced drug side effects and simplified dosing. Innovative techniques include antibody-mediated drug release, feedback-responsive delivery systems, manipulation of carrier-mediated transport, microspheres composed of polymers and liposomes, permeabilizers, selective delivery to localized sites and vectors to penetrate the blood-brain barrier. Several delivery systems have been approved and more are in clinical trials. Drug delivery system research has greatly influenced the management of brain tumors, central nervous system infections, chronic pain, drug addiction, epileptic disorders, migraine headaches, neurodegenerative diseases, schizophrenia, spasticity and stroke. For many disorders, optimization of drug delivery will continue to be the therapeutic focus for a long while.
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PMID:Innovations in drug delivery to the central nervous system. 1297 90

A case report and discussion of a 64-year-old white female who presented with uncontrolled pain in several body areas despite massive oral controlled release morphine use is presented. Her pain was not associated with much spasticity. This patient responded remarkably to intrathecal baclofen even after the opioid was tapered and discontinued. The potential usefulness of baclofen in seemingly opioid-resistant chronic pain is discussed.
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PMID:Pain relief from baclofen analgesia in a neuropathic pain patient who failed opioid and pharmacotherapy: case report. 1464 Mar 56

Chronic pain is a common secondary problem associated with cerebral palsy (CP). This pain may be due to the musculoskeletal problems that often accompany CP, including spasticity, scoliosis, and bony deformity. The purpose of this study was to determine the effects of biofeedback-assisted relaxation training on self-reported pain and muscle tension in 3 adults with CP using a multiple baseline design across subjects. Two of 3 participants reported decreases in their pain experiences posttreatment. Their subjective reports, however, did not correspond with physiological changes. Complications in the use of progressive relaxation exercises and EMG biofeedback equipment are described and suggestions for future research provided.
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PMID:Outcome of biofeedback-assisted relaxation for pain in adults with cerebral palsy: preliminary findings. 1520 76

While pain is a common problem in multiple sclerosis (MS) patients, it is frequently overlooked and has to be asked for actively. Pain can be classified into 4 diagnostically and therapeutically relevant categories. 1. PAIN DIRECTLY RELATED TO MS: Painful paroxysmal symptoms like trigeminal neuralgia or painful tonic spasms are treated with carbamazepine as first choice, or lamotrigine, gabapentin, oxcarbazepine and other anticonvulsants. Painful "burning" dysaesthesia, the most frequent chronic pain syndrome, are treated with tricyclic antidepressants or carbamazepine, further options include gabapentin or lamotrigine. While escalation therapy may require opioids, the role of cannabinoids in the treatment of pain still has to be determined. 2. PAIN INDIRECTLY RELATED TO MS: Pain related to spasticity often improves with adequate physiotherapy. Drug treatment includes antispastic agents like baclofen or tizanidine, alternatively gabapentin. In severe cases botulinum toxin injections or intrathecal baclofen merit consideration. Physiotherapy and physical therapy may ameliorate malposition-induced joint and muscle pain. Moreover, painful pressure lesions should be avoided using optimally adjusted aids. 3. Treatment-related pain can occur with subcutaneous injections of beta interferons or glatiramer acetate and may be reduced by optimizing the injection technique and by local cooling. Systemic side effects of interferons like myalgias can be reduced by paracetamol or ibuprofen. 4. Pain unrelated to MS such as back pain or headache are frequent in MS patients and may be worsened by the disease. Treatment should be follow established guidelines. In summary, a careful analysis of the pain syndrome will allow the design of the appropriate treatment plan using various medical and non-medical options and thus will help to ameliorate the patients' quality of life.
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PMID:[Therapy of pain syndromes in multiple sclerosis -- an overview with evidence-based recommendations]. 1588 Mar 5

Metabotropic gamma-aminobutyric acid(B) (GABAB) receptors for the major inhibitory transmitter GABA, together with metabotropic glutamate (mGLuRs) receptors, the extracellular calcium-sensing receptors (CaSRs), some V2R pheromone receptors and T1R taste receptors, belong to the family of 3 G-protein-coupled receptors (GPCRs). GABAB receptors are known to control neuronal excitability and modulate synaptic neurotransmission, playing a very important role in many physiological activities. These receptors are widely expressed and distributed in the nervous system and have been implicated in a variety of neurodegenerative and pathophysiological disorders including epilepsy, spasticity, chronic pain, depression, schizophrenia and drug addiction. To form a functional receptor entity, GABAB receptors must exist as a heterodimer consisting of GABAB1 and GABAB2 receptor subtypes with two 7-transmembrane proteins, and these subunits arise from distinct genes. The GABAB1 subunit binds the endogenous ligand within its extracellular N-terminus, whilst the GABAB2 subunit is not only essential for the correct trafficking of the GABAB1 subunit to the cell surface, but is also responsible for the interaction of the receptor with its cognate G-protein. Allosteric modulation has recently been recognized as an alternative pharmacological approach to gain selectivity in drug action. It is now generally accepted that modulators acting at the allosteric sites provide a novel perspective for the development of subtype-selective agents acting at GPCRs. These agents interact with allosteric binding sites quite separate from the highly conserved agonist binding region. In this review, we present a new class of phenylalkylamines, based on the lead compound fendiline, that are potent positive potentiators of GABAB receptor-mediated function and discuss their putative clinical applications. It is proposed that these new modulators may have therapeutic value in GABAB receptor pharmacology and are capable of selectively modifying GABAB receptor function. The allosteric modulators are offering an attractive and novel means to identify new leads, that are devoid of side effects associated with GABAB receptor agonists, and may, therefore, represent a major advance in the drug discovery process.
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PMID:Clinical potential of GABAB receptor modulators. 1638 96

Hip problems, including progressive subluxation, dislocation, and pain, are common in patients with cerebral palsy, particularly those who are nonambulatory with a large degree of spasticity. Clinical and radiographic screening facilitates early detection, and surgery is indicated to prevent progressive dysplasia. Although an early soft tissue release may prevent progressive subluxation in a subset of cases, bony reconstructive surgery is indicated for patients with established bony deformity. Salvage procedures are recommended to treat chronic pain caused by established subluxation or dislocation.
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PMID:Evaluation and treatment of hip dysplasia in cerebral palsy. 1663 49

Alpha(2) agonists have been in clinical use for decades, primarily in the treatment of hypertension. In recent years, alpha(2) agonists have found wider application, particularly in the fields of anesthesia and pain management. It has been noted that these agents can enhance analgesia provided by traditional analgesics, such as opiates, and may result in opiate-sparing effects. This has important implications for the management of acute postoperative pain and chronic pain states, including disorders involving spasticity or myofascial pain, neuropathic pain, and chronic daily headaches. The clinical utility of these agents is ever expanding, as they are gaining broader use in neuraxial analgesia, and new applications are continuously under investigation. The alpha(2) agonists that are currently employed in anesthesia and pain management include clonidine, tizanidine, and dexmedetomidine. Moxonidine and radolmidine, which are not currently in clinical use in humans, may offer favorable side-effect profiles when compared with traditional alpha(2) agonists, and may thereby allow for more widespread pain management applications.
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PMID:Alpha(2) receptors and agonists in pain management. 1701 39

Neuraxial drug administration describes techniques that deliver drugs in close proximity to the spinal cord, i.e. intrathecally into the CSF or epidurally into the fatty tissues surrounding the dura, by injection or infusion. This approach was initially developed in the form of spinal anaesthesia over 100 years ago. Since then, neuraxial drug administration has evolved and now includes a wide range of techniques to administer a large number of different drugs to provide anaesthesia, but also analgesia and treatment of spasticity in a variety of acute and chronic settings. This review concentrates on the pharmacological agents used and the clinical basis behind currently utilised approaches to neuraxial drug administration. With regard to local anaesthetics, the main focus is on the development of the enantiomer-specific compounds ropivacaine and levobupivacaine, which provide similar efficacy to bupivacaine with a reduced risk of severe cardiotoxicity. Opioids are the other group of drugs widely used neuraxially, in particular to provide analgesia alone or more commonly in combination with other agents. The physicochemical properties of the various opioids explain the main differences in efficacy and safety between these drugs when used intrathecally, of which morphine, fentanyl and sufentanil are most commonly used. Another group of drugs including clonidine, dexmedetomidine and epinephrine (adrenaline) provide neuraxial analgesia via alpha-adrenergic receptors and are used mainly as adjuvants to local anaesthetics and opioids. Furthermore, intrathecal baclofen is in routine clinical use to treat spasticity in a number of neurological conditions. Beside these established approaches, a wide range of other drugs have been assessed for neuraxial administration to provide analgesia; however, most are in various early stages of investigation and are not used routinely. These drugs include neostigmine, ketamine, midazolam and adenosine, and the conotoxin ziconotide. The latter is possibly the most unusual compound here; it has recently gained registration for intrathecal use in specific chronic pain conditions.
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PMID:Neuraxial drug administration: a review of treatment options for anaesthesia and analgesia. 1704 29

Intraspinal drug infusion using implantable pumps and catheter systems is a safe and effective therapy for selected pain patients with severe chronic pain. It improves pain relief, reduces drug-related side effects, decreases the need for oral analgesia and enhances quality of life in a segment of chronic pain patients whose pain has not been controlled with more conservative therapies. Intrathecal drug therapy has therefore established its role in the treatment of malignant pain, benign pain and severe spasticity.Careful patient selection and management as well as a multidisciplinary approach are determinants of successful treatment. Current practices for patient selection and management, screening, drug selection, dosing and implantation for intrathecal drug delivery systems are discussed.
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PMID:[Importance of intrathecal pain therapy]. 1726 12

Operative neuromodulation is the field of altering electrically or chemically the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks and produce therapeutic effects. It is a rapidly evolving biomedical and high-technology field on the cutting-edge of developments across a wide range of scientific disciplines. The authors review relevant literature on the neuromodulation procedures that are performed in the spinal cord or peripheral nerves in order to treat a considerable number of conditions such as (a) chronic pain (craniofacial, somatic, pelvic, limb, or due to failed back surgery), (b) spasticity (due to spinal trauma, multiple sclerosis, upper motor neuron disease, dystonia, cerebral palsy, cerebrovascular disease or head trauma), (c) respiratory disorders, (d) cardiovascular ischemia, (e) neuropathic bladder, and (f) bowel dysfunction of neural cause. Functional neuroprosthetics, a field of operative neuromodulation, encompasses the design, construction and implantation of artificial devices capable of generating electrical stimuli, thereby, replacing the function of damaged parts of the nervous system. The present article also reviews important literature on functional neuroprostheses, functional electrical stimulation (FES), and various emerging applications based on microsystems devices, neural engineering, neuroaugmentation, neurostimulation, and assistive technologies. The authors highlight promising lines of research such as endoneural prostheses for peripheral nerve stimulation, closed-loop systems for responsive neurostimulation or implanted microwires for microstimulation of the spinal cord to enable movements of paralyzed limbs. The above growing scientific fields, in combination with biological regenerative methods, are certainly going to enhance the practice of neuromodulation. The range of neuromodulatory procedures in the spine and peripheral nerves and the dynamics of the biomedical and technological domains which are reviewed in this article indicate that new breakthroughs are likely to improve substantially the quality of life of patients who are severely disabled by neurological disorders.
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PMID:An introduction to operative neuromodulation and functional neuroprosthetics, the new frontiers of clinical neuroscience and biotechnology. 1769 51


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