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

The spinal dorsal horn is known for its important functional role in the field of transmission and modulation of sensory afferents. Because of this, the dorsal horn represents a target for numerous analgesic and antispastic procedures. Thus, it would be interesting to develop imaging dedicated to this spinal structure. The purpose of this study was to investigate the radiologic anatomy of the cervical dorsal horn by magnetic resonance imaging (MRI) (1.5T). The first step consisted in the validation of the anatomic information provided by MRI on 5 human cadavers. A spin-echo sequence (T2, 2000/45) enabled the demonstration of good correlations between histologic sections and axial MRI slices performed at the corresponding cervical levels. The second step was the <<in vivo>> exploration of 20 subjects, aiming at the development of a gradient echo sequence (T2*) with a conventional MRI unit, compatible with a routine clinical examination. The dorsal horn was clearly identified in 77% of the axial slices performed (n = 300). The angle between the dorsal horn axis and the sagittal plane was measured as from 25.5 degrees at C2 to 40 degrees at C8 segments. The results of this anatomico-radiologic study of the cervical dorsal horn suggest that preoperative MRI could be useful to design the surgical approach to this structure, as performed during cervical microsurgical drezotomy (DREZ = dorsal root entry zone) for the treatment of selected cases of chronic pain or disabling spasticity in the upper limbs.
 ...
PMID:Radiologic anatomy of the spinal dorsal horn at the cervical level (anatomic-MRI correlations). 1095 72

The aim of this study was to develop, for the first time in the human spinal dorsal horn (DH), an in vivo method for the study of amino acids (AAs). A microdialysis technique was used to sample AAs in the extracellular fluid of the DH apex in eight patients in whom surgery in the dorsal root entry zone (DREZ) was performed. Before making microsurgical lesions, specific concentric-type microdialysis probes were implanted over a 60-minute period in the DREZ and directed to the DH apex (10 implantations). The AA concentrations in the dialysates were determined using high-performance liquid chromatography with fluorescence detection. The concentrations of excitatory AAs (glutamate and aspartate) and inhibitory AAs (gamma-aminobutyric acid and glycine) decreased and were stabilized by 45 minutes after probe implantation, whereas the levels of nonneurotransmitter AAs (alanine and threonine) were not stabilized at 60 minutes. The ability of the probe to track the changes of extracellular AAs was demonstrated. Neither intra- nor postoperative microdialysis-related complications were observed (with a follow up of 18 months). The present study demonstrates that microdialysis can be performed safely in the human DH during DREZ lesioning. Despite technical and analytical limitations related to the intraoperative conditions, this technique offers new possibilities for clinical research on neurotransmitters involved in some relevant pathological states, especially in chronic pain and spasticity.
 ...
PMID:Microdialysis study of amino acid neurotransmitters in the spinal dorsal horn of patients undergoing microsurgical dorsal root entry zone lesioning. Technical note. 1114 57

Spinal cord stimulation (SCS) is a reversible treatment for chronic pain that is gaining favor as a first-line therapy for many disease states. Because there are no addictive issues and no side effects systemically, the treatment is moving up the treatment continuum ladder. First used clinically in 1967, the procedure was used exclusively for failed back surgery syndrome. Over the past 30 years selection criteria, psychologic screening, and technology have improved. These advances have broadened the treatment options for many patients in pain. This review focuses on the selection, indications, techniques, new advances, complications, and outcomes involved with SCS. A review is provided for the treatment of radiculitis, failed back surgery syndrome, complex regional pain syndrome, peripheral neuropathies, pelvic pain, occipital neuralgia, angina, ischemic extremity pain, and spasticity. Technologic advances such as multi-lead and multi-electrode arrays are also discussed in regard to the impact these developments have on the clinical application of the therapy.
 ...
PMID:Current and future trends in spinal cord stimulation for chronic pain. 1167 84

Clinically significant pain has been found in as many as 65% of persons diagnosed with multiple sclerosis (MS). Acute pain conditions include trigeminal neuralgia, painful optic neuritis, and Lhermitte's syndrome. Chronic pain conditions such as dysesthesias in the limbs, joint pain, and other musculoskeletal or mechanical pain problems develop as a function of spasticity and deconditioning associated with MS. These painful conditions may respond to pharmacological, surgical, rehabilitation, and psychological interventions. However, unresolved pain, associated disability, and affective distress are common. In addition, efforts to manage MS and its associated symptoms, for example, may inadvertently cause osteoporosis and headache or other symptoms that may exacerbate pain and pain-related disability. Conversely, efforts to manage pain may have negative effects on the symptoms of MS (e.g., increased fatigue). A multidimensional approach to assessment and management that is guided by a comprehensive biopsychosocial model is recommended. Such an approach needs to consider the exacerbating nature of MS, MS-related pain, and interventions aimed at their management. Suggestions for future research on MS-related pain conclude the article.
 ...
PMID:Pain in multiple sclerosis: a biopsychosocial perspective. 1205 66

There is a large amount of evidence to support the view that the psychoactive ingredient in cannabis, delta9-tetrahydrocannabinol (delta9-THC), and cannabinoids in general, can reduce muscle spasticity and pain under some circumstances. Cannabinoid (CB1) receptors in the CNS appear to mediate both of these effects and endogenous cannabinoids may fulfil these functions to some extent under normal circumstances. However, in the context of multiple sclerosis (MS), it is still questionable whether cannabinoids are superior to existing, conventional medicationsfor the treatment of spasticity and pain. In the case of spasticity, there are too few controlled clinical trials to draw any reliable conclusion at this stage. In the case of pain, most of the available trials suggest that cannabinoids are not superior to existing treatments; however, few trials have examined chronic pain syndromes that are relevant to MS. Whether or not cannabinoids do have therapeutic potential in the treatment of MS, a further issue will be whether synthetic cannabinoids should be used in preference to cannabis itself. Smoking cannabis is associated with significant risks of lung cancer and other respiratory dysfunction. Furthermore, delta9-THC, as a broad-spectrum cannabinoid receptor agonist, will activate both CB1 and CB2 receptors. Synthetic cannabinoids, which target specific cannabinoid receptor subtypes in specific parts of the CNS, are likely to be of more therapeutic use than delta9-THC itself. If rapid absorption is necessary, such synthetic drugs could be delivered via aerosol formulations.
 ...
PMID:Cannabinoids in the treatment of pain and spasticity in multiple sclerosis. 1213 4

Untreated chronic pain is costly to society and to the individual suffering from it. The treatment of chronic pain, a multidimensional disease, should rely on the expertise of varying health care providers and should focus not only on the neurobiological mechanisms of the process but also on the psychosocial aspects of the disease. Implantable devices are costly and invasive, and such efficacious therapies should be used only when more conservative and less costly therapies have failed to provide relief of pain and suffering. Spinal cord stimulation provides neuromodulation of neuropathic, but not nociceptive, pain signals and when used for appropriate indications in the right individuals provides approximately 60-80% long-term pain relief in 60-80% of patients trialled for efficacy. Intrathecal therapies with opioids such as morphine, fentanyl, sufentanil or meperidine--or non-opioids such as clonidine or bupivacaine--provide analgesia in patients with nociceptive or neuropathic pain syndromes. Baclofen, intrathecally, provides profound relief of muscle spasticity due to multiple sclerosis, spinal cord injuries, brain injuries or cerebral palsy.
 ...
PMID:Implantable devices for pain control: spinal cord stimulation and intrathecal therapies. 1251 95

The paper is a review of current experience with use of gabapentin--a new antiepileptic drug--in neurologic conditions others than epilepsy. Mechanism of action of the drug is not fully elucidated yet. However it proved to be effective in therapy of chronic pain, especially in neuropathic pain, neuralgia, low back pain, reflex sympathetic dystrophy and erythromelalgia. Gabapentin is also effective in pain and spasticity in multiple sclerosis. Clinical studies of gabapentin in movement disorders, such as Parkinson disease, essential tremor and atrophic lateral sclerosis are discussed in the paper. It can be summarized that gabapentin is a valuable medication and the use thereof in neurology is not limited to epilepsy.
 ...
PMID:[GABApentin--new therapeutic possibilities]. 1252 21

Chronic low back pain is the second most common illness reported by patients in the United States and accounts for substantial morbidity and health-care resource utilization. Many back and spine stressors can contribute to tissue injury, resulting in acute or chronic pain. In response to injury, biochemical processes that cause inflammation and nerve sensitization increase pain levels and contribute to a cycle of reactivity that further heightens patients' sensitivity to pain stimuli. Treatment of back pain depends on its severity, duration, and underlying cause. Traditional therapeutic options include exercise, oral anti-inflammatory or analgesic medication, antidepressants, physical therapy and, in severe cases, surgery. Unfortunately, dissatisfaction with treatment of back pain is common. Oral medications may not completely alleviate symptoms, and opioid analgesics must be used with caution because of their addictive properties. Surgery does not always produce relief and, in some cases, may even exacerbate the problem. Botulinum toxin, which has already been shown to alleviate pain associated with cervical dystonia and other conditions characterized by muscle spasticity, is now being studied for the treatment of back pain. Preliminary evaluations have shown that this treatment is safe and has the advantage of providing local relief directly to the site of injury or pain, without causing systemic side effects. Initial data from small trials also suggest that botulinum toxin is effective, alleviating back pain in selected patients. On the basis of these promising results, additional study in larger trials is warranted.
 ...
PMID:A focused review of the use of botulinum toxins for low back pain. 1256 63

GW Pharmaceuticals is undertaking a major research programme in the UK to develop and market distinct cannabis-based prescription medicines [THC:CBD, High THC, High CBD] in a range of medical conditions. The cannabis for this programme is grown in a secret location in the UK. It is expected that the product will be marketed in the US in late 2003. GW's cannabis-based products include selected phytocannabinoids from cannabis plants, including D9 tetrahydrocannabinol (THC) and cannabidiol (CBD). The company is investigating their use in three delivery systems, including sublingual spray, sublingual tablet and inhaled (but not smoked) dosage forms. The technology is protected by patent applications. Four different formulations are currently being investigated, including High THC, THC:CBD (narrow ratio), THC:CBD (broad ratio) and High CBD. GW is also developing a specialist security technology that will be incorporated in all its drug delivery systems. This technology allows for the recording and remote monitoring of patient usage to prevent any potential abuse of its cannabis-based medicines. GW plans to enter into agreements with other companies following phase III development, to secure the best commercialisation terms for its cannabis-based medicines. In June 2003, GW announced that exclusive commercialisation rights for the drug in the UK had been licensed to Bayer AG. The drug will be marketed under the Sativex brand name. This agreement also provides Bayer with an option to expand their license to include the European Union and certain world markets. GW was granted a clinical trial exemption certificate by the Medicines Control Agency to conduct clinical studies with cannabis-based medicines in the UK. The exemption includes investigations in the relief of pain of neurological origin and defects of neurological function in the following indications: multiple sclerosis (MS), spinal cord injury, peripheral nerve injury, central nervous system damage, neuroinvasive cancer, dystonias, cerebral vascular accident and spina bifida, as well as for the relief of pain and inflammation in rheumatoid arthritis and also pain relief in brachial plexus injury. The UK Government stated that it would be willing to amend the Misuse of Drugs Act 1971 to permit the introduction of a cannabis-based medicine. GW stated in its 2002 Annual Report that it was currently conducting five phase III trials of its cannabis derivatives, including a double-blind, placebo-controlled trial with a sublingual spray containing High THC in more than 100 patients with cancer pain in the UK. Also included is a phase III trial of THC:CBD (narrow ratio) being conducted in patients with severe pain due to brachial plexus injury, as are two more phase III trials of THC:CBD (narrow ratio) targeting spasticity and bladder dysfunction in multiple sclerosis patients. Another phase III trial of THC:CBD (narrow ratio) in patients with spinal cord injury is also being conducted. Results from the trials are expected during 2003. Three additional trials are also in the early stages of planning. These trials include a phase I trial of THC:CBD (broad ratio) in patients with inflammatory bowel disease, a phase I trial of High CBD in patients with psychotic disorders such as schizophrenia, and a preclinical trial of High CBD in various CNS disorders (including epilepsy, stroke and head injury). GW Pharmaceuticals submitted an application for approval of cannabis-based medicines to UK regulatory authorities in March 2003. Originally GW hoped to market cannabis-based prescription medicines by 2004, but is now planning for a launch in the UK towards the end of 2003. Several trials for GW's cannabis derivatives have also been completed, including four randomised, double-blind, placebo-controlled phase III clinical trials conducted in the UK. The trials were initiated by GW in April 2002, to investigate the use of a sublingual spray containing THC:CBD (narrow ratio) in the following medical conditions: pain in spinal cord injury, pain and sleep in MS and spinal cord injury, neuropathic pain in MS and general neuropathic pain (presented as allodynia). Results from these trials show that THC:CBD (narrow ratio) caused statistically significant reductions in neuropathic pain in patients with MS and other conditions. In addition, improvements in other MS symptoms were observed as well. Phase II studies of THC:CBD (narrow ratio) have also been completed in patients with MS, spinal cord injury, neuropathic pain and a small number of patients with peripheral neuropathy secondary to diabetes mellitus or AIDS. A phase II trial of THC:CBD (broad ratio) has also been completed in a small number of patients with rheumatoid arthritis, as has a trial of High CBD in patients with neurogenic symptoms. A phase II trial has also been evaluated with High THC in small numbers of patients for the treatment of perioperative pain. The phase II trials provided positive results and confirmed an excellent safety profile for cannabis-based medicines. GW Pharmaceuticals received an IND approval to commence phase II clinical trials in Canada in patients with chronic pain, multiple sclerosis and spinal cord injury in 2002. Following meetings with the US FDA, Drug Enforcement Agency (DEA), the Office for National Drug Control Policy, and National Institute for Drug Abuse, GW was granted an import license from the DEA and has imported its first cannabis extracts into the US. Preclinical research with these extracts in the US is ongoing.
 ...
PMID:Cannabis-based medicines--GW pharmaceuticals: high CBD, high THC, medicinal cannabis--GW pharmaceuticals, THC:CBD. 1295

In spite of the proven efficacy of the newer immunomodulative pharmacologic treatments for multiple sclerosis, such as steroid pulse therapy for exacerbation and beta-interferon subcutaneous injections for prevention, those treatments have not yet satisfied the criteria for direct management of the disease. Thus, even now, patients with multiple sclerosis still need symptomatic therapy to improve their quality of life and ameliorate the impairments in their activities of daily living due to their various neurologic deficits. This article reviews the management of a wide range of neurologic symptoms of multiple sclerosis, including spasticity, bladder dysfunction, paroxysmal symptoms, and chronic pain.
 ...
PMID:[Symptomatic therapies for multiple sclerosis]. 1296 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>