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)

Intrathecal baclofen (ITB) has evolved into a standard treatment for severe spasticity of both spinal and cerebral origin. The accumulated promising data from reported series of patients receiving ITB therapy together with the fact that spastic hypertonia commonly coexists with other neurological disorders have constituted a solid basis for offering this kind of treatment to patients suffering from other movement disorders. These include motor disorders such as dystonia, amyotrophic lateral sclerosis, status dystonicus, Hallervorden-Spatz disease, Freidreich's ataxia, "stiff-man" syndrome, but also vegetative states after revere brain trauma, anoxic encephalopathy or other pathology and more recently, various chronic pain syndromes. In this article, on the basis of the established applications of ITB therapy, we review the important emerging indications of this rewarding neuromodulation method and attempt to identify its future potential beneficial role in other chronic and otherwise refractory neurological disorders.
 ...
PMID:Intrathecal baclofen in current neuromodulatory practice: established indications and emerging applications. 1769 70

Intrathecal baclofen (ITB) administration is a fully established treatment for severe spasticity. However, it is not widely known that baclofen, an agonist of the GABA-B receptor, has additional beneficial effects in other conditions such as chronic pain, coma, dystonia, tetanus, and hyypothalamic storm. Sporadic cases of dramatic recovery from persistent vegetative state after intrathecal administration of baclofen have been reported. There have been also reports on the use of baclofen for control of dystonia due to cerebral palsy, neuropathic central pain syndrome or reflex sympathetic dystrophy. On the other hand, epidural spinal cord stimulation (SCS) has been used in the management not only of pain but also of spasticity, dystonia, and in order to improve deteriorated consciousness, but the effects so far have been modest and variable. Similarities between ITB and SCS are interesting as both involve the spinal GABAergic system. Based on a 15-year personal experience of intrathecal baclofen, I would stress the importance of this treatment not only for spasticity but also for other difficult neurological disorders.
 ...
PMID:Intrathecal baclofen in the treatment of post-stroke central pain, dystonia, and persistent vegetative state. 1769 81

Cannabis sativa L. is possibly one of the oldest plants cultivated by man, but has remained a source of controversy throughout its history. Whether pariah or panacea, this most versatile botanical has provided a mirror to medicine and has pointed the way in the last two decades toward a host of medical challenges from analgesia to weight loss through the discovery of its myriad biochemical attributes and the endocannabinoid system wherein many of its components operate. This study surveys the history of cannabis, its genetics and preparations. A review of cannabis usage in Ancient Egypt will serve as an archetype, while examining first mentions from various Old World cultures and their pertinence for contemporary scientific investigation. Cannabis historians of the past have provided promising clues to potential treatments for a wide array of currently puzzling medical syndromes including chronic pain, spasticity, cancer, seizure disorders, nausea, anorexia, and infectious disease that remain challenges for 21st century medicine. Information gleaned from the history of cannabis administration in its various forms may provide useful points of departure for research into novel delivery techniques and standardization of cannabis-based medicines that will allow their prescription for treatment of these intractable medical conditions.
 ...
PMID:History of cannabis and its preparations in saga, science, and sobriquet. 1771 11

Recent years have seen a dramatic increase in the number of clinical trials investigating the potential efficacy of medicinal cannabinoids for the symptomatic treatment of chronic pain and spasticity in multiple sclerosis (MS). A number of different cannabinoids have been used, including: delta9-tetrahydrocannabinol (THC) itself; the synthetic delta9-THC, dronabinol; a 1:1 ratio of delta9-THC:cannabidiol (Sativex); and the synthetic delta9-THC metabolites CT-3 and nabilone. Other Cannabis extracts have also been tested. While 2-3 years ago there was little consensus in the literature, now the majority of studies are beginning to suggest that cannabinoids are useful in the treatment of MS in at least a subset of individuals. Their adverse side-effect profile has generally been mild compared with other drugs used for pain and spasticity; nonetheless, there is still concern about potential long-term side effects, particularly psychiatric side effects and effects on fetal development.
 ...
PMID:Symptomatic treatment of multiple sclerosis using cannabinoids: recent advances. 1786 14

Voltage gated sodium channels play important roles both in vital physiological functions and several pathological processes of the central nervous system. Epilepsy, chronic pain, neurodegenerative diseases, and spasticity are all characterized by an over-excited state of specific groups of central neurons that is accompanied by an abnormally increased activity of sodium channels. An efficient strategy of controlling such diseases is to use blockers that preferentially act on these over-excited cells. State dependently acting agents, such as phenytoin, or lamotrigine, leave normal physiological functions relatively intact, resulting in a favorable therapeutic window. Nine isoforms of the channel forming alpha subunit are known, which show distinct expression patterns in different tissues. Another possible way to decrease the chance of adverse effects is to develop agents selectively inhibiting the channel subtype involved in the pathomechanism of the disease to be treated. Many recent patents claim sodium channel blockers with improved characteristics regarding state dependency or subtype selectivity. Such agents may offer a breakthrough in the treatment of a variety of central nervous system diseases. This review focuses on the current trends in sodium channel research, surveying the traditional and newly emerging therapeutic fields, and the diverse medicinal chemistry of sodium channel blockers.
 ...
PMID:Blockers of voltage-gated sodium channels for the treatment of central nervous system diseases. 1822 Dec 18

While pain is a common problem in patients with multiple sclerosis (MS), it is not frequently mentioned by patients and a more direct approach is required in order to obtain information about pain from patients. Many patients with MS experience more than one pain syndrome; combinations of dysaesthesia, headaches and/or back or muscle and joint pain are frequent. For each pain syndrome a clear diagnosis and therapeutic concept needs to be established. Pain in MS can be classified into four diagnostically and therapeutically relevant categories: (i) neuropathic pain due to MS (pain directly related to MS); (ii) pain indirectly related to MS; (iii) MS treatment-related pain; and (iv) pain unrelated to MS. Painful paroxysmal symptoms such as trigeminal neuralgia (TN), or painful tonic spasms are treated with antiepileptics as first choice, e.g. carbamazepine, oxcarbazepine, lamotrigine, gabapentin, pregabalin, etc. Painful 'burning' dysaesthesias, the most frequent chronic pain syndrome, are treated with TCAs such as amitriptyline, or antiepileptics such as gabapentin, pregabalin, lamotrigine, etc. Combinations of drugs with different modes of action can be particularly useful for reducing adverse effects. While escalation therapy may require opioids, there are encouraging results from studies regarding cannabinoids, but their future role in the treatment of MS-related pain has still to be determined. Pain related to spasticity often improves with adequate physiotherapy. Drug treatment includes antispastic agents such as baclofen or tizanidine and in patients with phasic spasticity, gabapentin or levetiracetam are administered. In patients with severe spasticity, botulinum toxin injections or intrathecal baclofen merit consideration. While physiotherapy may ameliorate malposition-induced joint and muscle pain, additional drug treatment with paracetamol (acetaminophen) or NSAIDs may be useful. Moreover, painful pressure lesions should be avoided by using optimally adjusted aids. Treatment-related pain associated with MS can occur with subcutaneous injections of interferon-beta or glatiramer acetate, and may be reduced by optimizing the injection technique and by local cooling. Systemic (particularly 'flu-like') adverse effects of interferons, e.g. myalgias, can be reduced by administering paracetamol, ibuprofen or naproxen. A potential increase in the frequency of pre-existing headaches after starting treatment with interferons may require optimization of headache attack therapy or even prophylactic treatment. Pain unrelated to MS, such as back pain or headache, is common in patients with MS and may deteriorate as a result of the disease. In summary, a careful analysis of each pain syndrome will allow the design of the appropriate treatment plan using various medical and nonmedical options (multimodal therapy), and will thus help to improve the quality of life (QOL) of the patients.
 ...
PMID:Current management of pain associated with multiple sclerosis. 1833 59

Nociceptive stimuli are modulated at the dorsal horn of the spinal cord. This modulation is performed by various systems working independently complementarily, additively or supra-additively. Non-opioid analgesics relieve pain without a motor blockade. In contrast to spinal opioids a reduced risk of respiratory depression is expected. In the therapy of chronic pain non-opioid analgesics may be an alternative, given alone or in combination with an opioid. Clinically relevant dosages for antinociception mediated by the alphaadrenoceptoragonistclonidine are >/=150 mug epidurally. Clonidine is effective in reducing acute and chronic pain. In combination with opioids the action of the opioids is intensified. Clonidine intensifies and prolongs the action of local anesthetics. If opioid tolerance occurs, epidural clonidine alone or in combination with an opioid has good antinociceptive action.Midazolam, a water-soluble benzodiazepine, was injected spinally for the reduction of pain for various indications (postoperative, malignancy, chronic back pain, spinal spasticity). Spinal benzodiazepine should not be injected into the spine in patients until it has been proven that there are no neurotoxic effects. Intrathecally injectedbaclofen is a well-known means of reducing spinal spasticity. Used in this way, it may have a secondary analgesic effect. No significant direct analgesic effect has so far been demonstrated. Spinalcalcitonin often leads to insufficient pain relief when given alone. Combination with an opioid may reduce the dosage of the opioid. Nausea and vomiting are frequent side effects of spinal calcitonin. Intrathecalsomatostatin produces antinociception. However, in animal studies neurotoxic action has been observed. Administration in man has not yet been proved to be safe. Spinalketamine has procluted controversial results in clinical studies, and has not yet been excluded that the substance is not neurotoxic.Lysine acetylsalicylic acid (L-ASA) has been given intrathecally for the therapy of severe cancer pain and chronic back pain. In most patients good analgesia was observed up to 2 months after a single injection. If neurotoxity can be excluded, L-ASA may be an alternative in the therapy of cancer pain before neurodestructive therapy is done.
 ...
PMID:[Intrathecal and epidural administration of non-opioid analgesics in acute and chronic pain treatment.]. 1841 40

A significant proportion of chronic pain is of musculoskeletal origin. Botulinum toxin (BTX) has been successfully used in the treatment of spasmodic torticollis, limb dystonia, and spasticity. Investigators have, thus, become interested in its potential use in treating many chronic pain conditions. Practitioners have used BTX, outside the product license, in the treatment of refractory myofascial pain syndrome and neck and low back pain (LBP). This article reviews the current evidence relating to chronic pain practice. There is evidence supporting the use of both BTX type A and type B in the treatment of cervical dystonias. The weight of evidence is in favor of BTX type A as a treatment in: pelvic pain, plantar fasciitis, temporomandibular joint dysfunction associated facial pain, chronic LBP, carpal tunnel syndrome, joint pain, and in complex regional pain syndrome and selected neuropathic pain syndromes. The weight of evidence is also in favor of BTX type A and type B in piriformis syndrome. There is conflicting evidence relating to the use of BTX in the treatment whiplash, myofascial pain, and myogenous jaw pain. It does appear that BTX is useful in selected patients, and its duration of action may exceed that of conventional treatments. This seems a promising treatment that must be further evaluated.
 ...
PMID:Evidence for the use of botulinum toxin in the chronic pain setting--a review of the literature. 1850 28

The voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability. Abnormal activity of sodium channels is related to several pathological processes, including cardiac arrhythmias, epilepsy, chronic pain, neurodegenerative diseases and spasticity. In view of this, VGSCs are considered important therapeutic targets for the treatment of these disorders. To date, nine VGSC isoforms have been identified and have a distinct pattern of expression within the human body. In addition, VGSCs also have distinct electrophysiological profiles with differing activation and inactivation states. As such, there is a concerted effort to develop not only isoform selective antagonists, but also antagonists that exhibit state selectivity, particularly to the inactivated state of the channel. This review will provide a brief historical prospective and will primarily focus on recent advances in the development of isoform specific and state selective sodium channel antagonists and the medicinal chemistry involved, surveying the emerging therapeutic fields.
 ...
PMID:Recent advances in the medicinal chemistry of sodium channel blockers and their therapeutic potential. 1944 9

Since the late 1970s, local injections of BoNT have provided clinical benefit for patients with inappropriately contracting muscles with or without pain or sensory disturbance. Marketing authorization for some BoNTs, depending on country, include core indications of dystonia (blepharospasm and cervical dystonia), large muscle spastic disorders (not yet approved in the United States, e.g., adult post-stroke spasticity and equinus foot deformity), hyperhidrosis and aesthetic. Subsequent development has extended to selected conditions characterized by recurrent or chronic pain (migraine headache), and urologic indications (neurogenic/idiopathic overactive bladder; prostate hyperplasia), with multiple additional opportunities available. Portfolio management requires a careful individual opportunity assessment of scientific and technical aspects (basic science foundation, potential to treat unmet medical need, product-specific risk in specific populations, therapeutic margin/safety profile, and probability of successful registration pathway). This article describes ongoing development targets for BOTOX.
 ...
PMID:Development of future indications for BOTOX. 1947 Mar 42


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