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)

Mitochondrial myopathies make up a group of rare disorders whose onset is in childhood or adolescence. Muscle and central nervous system involvement is variable. Mitochondrial respiratory chain complex III deficiency (coenzyme Q - cytochrome C reductase) can manifest as exercise intolerance, myopathy, encephalopathy, and myocardial disease. Approximately 38 patients with complex III deficiency have been described since 1966, yet only a single anesthetic experience (epidural analgesia for cesarean delivery) has been reported. We describe the case of an 11-year-old boy with mitochondrial respiratory chain complex III deficiency, severe myopathy, and moderate encephalopathy who underwent surgery to improve right ischiotibial muscle spasticity. Monitoring included electrocardiography, noninvasive blood pressure, oxygen saturation by pulse oximetry, end-tidal carbon dioxide pressure, esophageal temperature, spirometry, and neuromuscular block (Relaxograph Datex). Midazolam, fentanyl, and propofol were used for anesthetic induction; mivacurium was used during intubation. Anesthetic maintenance was with propofol in continuous infusion and fractionated doses of fentanyl and mivacurium on demand in a mixture of oxygen and air. The boy's response to mivacurium was abnormal but he could nevertheless be extubated in the operating room at a train-of-four ratio of 75% and with no need to reverse the neuromuscular blockade. There were no problems during the anesthetic procedure, so it could be a good technique for these patients, despite of considering individually every case and extension of syntomatology, due to the little experience in anesthesia with deficiency of Complex III.
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PMID:[Anesthesia for a patient with mitochondrial respiratory chain complex III deficiency]. 1729 35

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.
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PMID:History of cannabis and its preparations in saga, science, and sobriquet. 1771 11

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.
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PMID:[Intrathecal and epidural administration of non-opioid analgesics in acute and chronic pain treatment.]. 1841 40

Adjuvant analgesics are drugs that are not primarily used as analgesics but can produce analgesia in certain types of pain. Adjuvant analgesics can be administered together with non-opioid and opioid analgesics on each step of the WHO analgesic ladder. They should be given when an additional or specific indication exists, but should not be used as a substitute for a thorough treatment with opioids and nonopioids. Adjuvant analgesics can be classified into groups according to the type of pain to be treated: continuous neuropathic pain or lancinating neuropathic pain, sympathetically maintained pain, bone pain and those for multipurpose use. Adjuvant drugs used for continuous neuropathic pain include local anaesthetics, clonidine, capsaicin, and antidepressants. Tricyclic antidepressants are the group that have been best investigated, and are therefore the drugs of choice. An analgesic effect is probably produced via enhancement of transmitter concentrations in pain-modulating pathways. This occurs at lower doses than those necessary to treat depression. Anticholinergic actions, acute glaucoma, constipation, orthostatic hypotension and cardiac arrhythmias are adverse effects that are seen predominantly with teritiary amine drugs and less often with secondary amine compounds. Initial doses should be small to avoid these adverse effects. Local anaesthetics are used less often, because of the high incidence of side effects (especially with tocainide, flecainide). An analgesic effect has been described in neuropathic pain, however, probably due to membrane stabilization and reduction of aberrant signal conduction. Mexiletine is considered to be the safest local anaesthetic, and should be used initially in small doses (100-150 mg/d). If side effects do not occur, doses can be increased step-wise up to 900 mg/d. Local anaesthetics are indicated for the treatment of severe neuropathic pain; this treatment is contraindicated in patients with cardiac arrhythmias. Systemic or intrathecal clonidine can be tried in neuropathic pain refractory to opioid therapy. The same stands for the topical application of capsaicin in certain types of pain. Lancinating neuropathic pain is an indication for anticonvulsant drugs. Carbamazepine, clonazepam, valproate and phenytoin seem to reduce aberrant signal conduction in damaged nerves in a manner similar to the supression of epileptiform activities in the brain. Common side effects include sedation, dizziness and nausea. Of greater concern are the more severe side effects, such as bone marrow depression (carbamazepine) and hepatotoxicity (phenytoin, valproate). Low initial doses and stepwise increases in dosage, repeated blood counts, and monitoring of plasma levels are helpful in recognizing and avoiding these adverse effects. Baclofen, a GABA agonist primarily used for spasticity, is effective in the treatment of trigeminal neuralgia and is often used in the management of lancinating pain of unspecific origin. The initial dosage is 10-15 mg/d, increasing to 30-90 mg/d, or higher. If neural blockade fails to reduce sympathetically maintained pain sufficiently specific adjuvants can be used. Sympatholytic drugs, e.g. phenoxybenzamine (60-120 mg/d) or prazosin, can be administered to patients without major cardiovascular dysfunction. There is experimental evidence of the involvement of calcium channels in nociception, and a beneficial clinical effect of nifidepine in reflex sympathetic dystrophy (RDS) has been demonstrated. Bone pain is common in tumor patients and can often be treated effectively with non-steroidal anti-inflammatory drugs. Biphosphonates (etidronate, clodronate, pamidronate derivates) also produce analgesic effects in patients with bone metastases. However, differences among the various compounds have not been clearly evaluated yet. Potent and specific radioisotopes are still under development and the use of calcitonin in bone pain is considered controversial.
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PMID:[Pharmacotherapy of cancer pain. 3. Adjuvant drugs.]. 1841 35

A 28-year-old woman in active labor at 38 weeks of gestation requested epidural analgesia. She had previously received an intrathecal baclofen infusion pump to relieve the spasticity of cerebral palsy. She had right hemiparesis and cerebral palsy but was otherwise healthy. The patient had been seen one month before her expected delivery date by a staff anesthesiologist. A lumbar X-ray demonstrated the intrathecal catheter entering the L3-4 interspace and extending to the mid-thoracic region. For labor analgesia the epidural space was identified at L4-5 with the patient sitting, using a standard 17-gauge Tuohy needle. An epidural catheter was threaded to 5 cm and provided effective analgesia until delivery four hours later. There were no postnatal complications.
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PMID:Epidural analgesia in labor for a woman with an intrathecal baclofen pump. 1902 55

Cannabis (marijuana) has been used for medicinal purposes for millennia, said to be first noted by the Chinese in c. 2737 BCE. Medicinal cannabis arrived in the United States much later, burdened with a remarkably checkered, yet colorful, history. Despite early robust use, after the advent of opioids and aspirin, medicinal cannabis use faded. Cannabis was criminalized in the United States in 1937, against the advice of the American Medical Association submitted on record to Congress. The past few decades have seen renewed interest in medicinal cannabis, with the National Institutes of Health, the Institute of Medicine, and the American College of Physicians, all issuing statements of support for further research and development. The recently discovered endocannabinoid system has greatly increased our understanding of the actions of exogenous cannabis. Endocannabinoids appear to control pain, muscle tone, mood state, appetite, and inflammation, among other effects. Cannabis contains more than 100 different cannabinoids and has the capacity for analgesia through neuromodulation in ascending and descending pain pathways, neuroprotection, and anti-inflammatory mechanisms. This article reviews the current and emerging research on the physiological mechanisms of cannabinoids and their applications in managing chronic pain, muscle spasticity, cachexia, and other debilitating problems.
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PMID:Medicinal use of cannabis in the United States: historical perspectives, current trends, and future directions. 1966 25

Evidence is emerging for the use of botulinum neurotoxin type-A (BoNT-A) for niche indications including pain independent of spasticity. Pain indications such as chronic nociceptive back pain, piriformis syndrome, chronic myofascial pain, pelvic pain, complex regional pain syndrome, facial pain and neuropathic pain are outlined in this paper. Of these, class I evidence is available for the treatment of chronic nociceptive low back pain, piriformis syndrome, myofascial pain, facial pain, neuropathic pain and plantar fasciitis. Peri-operative use of BoNT-A is emerging, with indications including planning for surgery and facilitating surgery, as well as healing and improving analgesia post-operatively. Evidence is limited, although there are some reports that clinicians are successfully using BoNT-A peri-operatively. There is class I evidence showing pre-operative use of BoNT-A has a beneficial effect on outcomes following adductor-release surgery. The use of BoNT for treatment of tremor, other than neck tremor in the setting of cervical dystonia, including evidence for upper limb tremor, cranial tremor and non-dystonic neck tremor is reviewed. The evidence is variable at this stage, and further study is required to develop definitive recommendations for the clinical utility of BoNT-A for these indications.
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PMID:Botulinum toxin assessment, intervention and aftercare for paediatric and adult niche indications including pain: international consensus statement. 2063 83

This paper reviews data supporting the existence of individual, predictable, and unpredictable fluctuations in the severity of chronic pain and spasticity. It also evaluates what is known on the use of implantable programmable drug delivery systems for the management of predictable fluctuations in pain and spasticity. In addition to fixed rate infusion pumps, programmable drug delivery systems have been developed over the past 20 years for the management of predictable pain or spasticity fluctuations. The published literature on experimental and clinical studies of those topics is reviewed and evaluated. Programmable drug delivery systems can tailor dosing to a patient's individual pattern of symptoms, providing more medication during peak intensity of symptoms and less medication when symptoms are reduced. Fluctuations in either pain or spasticity are difficult to predict precisely, and therefore even programmable pumps cannot administer the appropriate amount of medication at any particular time. Ideally, the patient should be able to treat unpredictable fluctuations in symptoms, and a combination of patient controlled analgesia (PCA) with programmable drug delivery systems is currently in development. The future management of unpredictable fluctuations in the intensity of chronic pain and spasticity was subjected to critical evaluation. There seems to be a general agreement on the clinical importance of these phenomena, but stronger evidence is needed for a widespread change in the current management of most chronic pain patients.
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PMID:Making a case for programmable pumps over fixed rate pumps for the management of fluctuations in chronic pain and spasticity: a literature review. 2215 47

A 7-year-old boy, weighing 18 kg, was diagnosed with maple syrup urine disease (MSUD). He suffered from spasticity of the lower limbs and pain that did not respond to oral medications. Injections of botulinum toxin A (BTX-A) at 10 sites and epidural analgesia with 0.125% bupivacaine were used to treat spasticity with good results. We conclude that BTX-A combined with epidural analgesia may be a useful treatment option for incapacitating, painful spasticity related to MSUD. This treatment modality allowed a comprehensive rehabilitation program to be completed and it lasted longer than 9 months.
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PMID:The use of botulinum toxin and epidural analgesia for the treatment of spasticity and pain in a patient with maple syrup urine disease. 2275 48

The K(+)-Cl(-) cotransporter KCC2 is responsible for maintaining low Cl(-) concentration in neurons of the central nervous system (CNS), which is essential for postsynaptic inhibition through GABA(A) and glycine receptors. Although no CNS disorders have been associated with KCC2 mutations, loss of activity of this transporter has emerged as a key mechanism underlying several neurological and psychiatric disorders, including epilepsy, motor spasticity, stress, anxiety, schizophrenia, morphine-induced hyperalgesia and chronic pain. Recent reports indicate that enhancing KCC2 activity may be the favored therapeutic strategy to restore inhibition and normal function in pathological conditions involving impaired Cl(-) transport. We designed an assay for high-throughput screening that led to the identification of KCC2 activators that reduce intracellular chloride concentration ([Cl(-)]i). Optimization of a first-in-class arylmethylidine family of compounds resulted in a KCC2-selective analog (CLP257) that lowers [Cl(-)]i. CLP257 restored impaired Cl(-) transport in neurons with diminished KCC2 activity. The compound rescued KCC2 plasma membrane expression, renormalized stimulus-evoked responses in spinal nociceptive pathways sensitized after nerve injury and alleviated hypersensitivity in a rat model of neuropathic pain. Oral efficacy for analgesia equivalent to that of pregabalin but without motor impairment was achievable with a CLP257 prodrug. These results validate KCC2 as a druggable target for CNS diseases.
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PMID:Chloride extrusion enhancers as novel therapeutics for neurological diseases. 2428 79


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