Pain Management Principles In Parkinson’s Disease
Non-pharmacologic methods with a multidisciplinary pain team should be utilized to provide optimal multimodal treatment in patients with PD.4 Muscle relaxation exercises and walking regularly can improve flexibility and dampen experiences of pain associated with motor symptoms.6 Rehabilitation with a physical therapist can improve gait and balance, targeting pain caused by motor symptoms. Surgical interventions, such as deep brain stimulation or an implanted spinal cord stimulator, may be appropriate for those patients experiencing pain with PD who do not respond to pharmacologic or rehabilitation interventions.1,6,9
Optimization of treatment with levodopa and other antiparkinsonian medications should be the first pharmacological step in managing PD-related pain.6,8 Beyond this recommendation, no evidence encourages the use of specific analgesic agents in any stepwise order, making patient input and assessment of pain type critical to appropriate treatment.
Patients should be prescribed analgesics if optimization of dopaminergic agents is not effective on its own .4
Optimization of Dopaminergic Agents
Safinamide is a selective, reversible MAO-B inhibitor that reduces degradation and reuptake of dopamine to increase levels in the striatum.19 Safinamide also has non-dopaminergic properties that modulate glutamate release via inhibition of voltage-gated sodium channels. This dual mechanism may mitigate pain, especially during off periods.
Measurement Of Reactive Oxygen Species
SH-SY5Y cells cultured in 24-well plates were treated with appropriate chemicals. After the treatment, cells were washed with Hanks balanced salt solution two times and incubated with DCF-DA for 30 min. After the medium was removed, cells were washed with PBS and solubilized in 200 l lysis buffer . After incubation for 10 min on ice, the cells were harvested and transferred to a black 96-well plate. DCF fluorescence was used as an indicator of reactive oxygen species . The plates were read at ex=485 nm and em=530 nm using a spectrofluorometer .
Side Effects And Complications
Amitriptyline is associated with a host of side effectsmost relatively common and mild, others more serious.
You should see a healthcare provider or go to the nearest hospital emergency department right away if you develop any serious symptoms after taking amitriptyline. Similarly, if you experience mild side effects that become severe or don’t go away, let your healthcare provider know.
Pain or tingling in hands or feet
Changes in sexual function
Rapid, pounding, or irregular heartbeat
Severe skin rash or hives
Swelling of the face and tongue
Yellowing of skin or eyes
Spasms of the jaw, neck, and/or back muscles
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How To Cope With Side Effects Of Amitriptyline
What to do about:
- constipation eat more high-fibre foods such as fresh fruit and vegetables and cereals. Try to drink several glasses of water or other non-alcoholic drinks every day. If you can, it may also help to do some exercise.
- dizziness this is probably due to low blood pressure. Drink plenty of water or other non-alcoholic drinks. Do not stand up too quickly after you have been sitting or lying down.
- dry mouth try sugar-free gum or sugar-free sweets.
- feeling sleepy or tired take amitriptyline in the evening and cut down on the amount of alcohol you drink. Do not drive, cycle or use tools or machinery if you’re feeling this way.
- difficulty peeing relax when you try to pee. Do not try to force the flow of urine. If you still cannot go, try again later. Talk to your doctor urgently if you cannot pee at all.
- headaches make sure you rest and drink plenty of fluids. Do not drink too much alcohol. Try taking paracetamol or ibuprofen if you need pain relief. Talk to your doctor if the headaches last longer than a week or are severe.
Cautions With Other Medicines
Many medicines and amitriptyline can affect each other and increase the chances of side effects.
Always check with your doctor or a pharmacist before starting any new medicine while you are taking amitriptyline.
Tell your doctor if you have ever taken any medicines for depression. Some antidepressants can affect the way amitriptyline works to cause very high blood pressure. This can happen even after you have stopped taking them.
Amitriptyline And Desipramine Induced Sh
To examine whether amitriptyline and desipramine are cytotoxic to SH-SY5Y cells, the viability of the cultured cells was measured following amitriptyline or desipramine treatment for 24 h. As shown in , amitriptyline and desipramine induced cell death in a dose-dependent manner. Amitriptyline induced approximately 4050% cell death at a 60 M concentration and desipramine at a 50 M concentration. To examine if the TCA-induced cell death is caspase-dependent, the cells were preincubated with the pan-caspase inhibitor zVAD-fmk and then treated with the drugs. Notably, cell death induced by amitriptyline or desipramine was not suppressed by the pan-caspase inhibitor, suggesting that the observed cell death may not be caspase-dependent apoptosis. To examine the mode of cell death induced by these TCAs, cells were preincubated with poly polymerase-1 inhibitor 3AB , ALLM, which inhibits calpain and cathepsin B/L , or E64, which inhibits cathepsin K/L/S/B/H . In addition, the cell death induced by amitriptyline or desipramine was not suppressed by an autophagy inhibitor 3-MA . As shown in , none of the inhibitors of known death-inducing enzymes or pathways suppressed TCA-induced cell death.
Why Is This Medication Prescribed
The combination of levodopa and carbidopa is used to treat the symptoms of Parkinson’s disease and Parkinson’s-like symptoms that may develop after encephalitis or injury to the nervous system caused by carbon monoxide poisoning or manganese poisoning. Parkinson’s symptoms, including tremors , stiffness, and slowness of movement, are caused by a lack of dopamine, a natural substance usually found in the brain. Levodopa is in a class of medications called central nervous system agents. It works by being converted to dopamine in the brain. Carbidopa is in a class of medications called decarboxylase inhibitors. It works by preventing levodopa from being broken down before it reaches the brain. This allows for a lower dose of levodopa, which causes less nausea and vomiting.
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Innovative Treatment Modalities For Managing Pain In Parkinson’s
Non-dopaminergic pharmacotherapy may benefit patients with PD-related pain. Botulinum toxin , both A and B derivatives, should be considered in patients who do not respond to dopaminergic treatment optimization.1,8 Botulinum toxin injection provides localized treatment by blocking the release of acetylcholine at the neuromuscular junction.4 Local injections of BTX type A or B can be effective for persistent dystonia-related pain and central pain, based on its neuromuscular action in movement disorders plus analgesic mechanism.
A randomized, double-blind, crossover, placebo-controlled trial concluded that BTX-A in patients with PD is safe and potentially useful in treating limb pain.29 The study was conducted in patients with PD over the age of 30 years with painful limbs not responding to the optimization of anti-Parkinsonian medications. Patients were randomized to receive BTX-A injection or placebo, followed by the other treatment per the crossover design. Depending on the location of pain, patients received up to 200 units in upper limbs or up to 300 units in lower limbs. Patients experienced a significant reduction in their self-reported numerical pain score 4 weeks after the BTX-A injection , but not with placebo . There was no difference between the change with BTX-A compared to placebo . This study demonstrated that targeted BTX-A injections are safe in patients with PD.
Amitriptyline As A Dopamine Neuroprotective Therapy
Objective/Rationale:The project proposes to repurpose the tricyclic antidepressant medication, amitriptyline , as a disease-modifying therapy for Parkinsons disease . AMI is an FDA-approved medication that has been in use since 1961. Recent evidence in pre-clinical models of PD and retrospective analysis of clinical data suggests that AMI has pharmacological properties distinct from other antidepressant medications that makes it more effective in treating depression in PD and may serve as a neuroprotectant for the dopamine neurons endangered in PD.
Project Description:Using a pre-clinical 6-hydroxydopamine toxin model that produces progressive degeneration of the dopamine system, we will perform a dose-finding and timing study comparing AMI to another tricyclic medication, nortriptyline, and to a non-tricyclic antidepressant drug, venlafaxine, for the capacity to protect the dopamine system during the process of degeneration. Analyses will use behavior, microscopy with cell counting, and biochemical measures.
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How Does Amitriptyline Work
Amitriptyline is a type of medicine called a tricyclic antidepressant . These medications work by increasing certain brain chemicals called neurotransmitters like serotonin and norepinephrine to help improve mood, sleep, pain, and anxiety.
Its not clear exactly how amitriptyline works for sleep, but one of its effects is to block histamine, which may result in drowsiness. This is one reason doctors prescribe amitriptyline as a sleep aid.
Animal Care And Amitriptyline Injection
All animal use complied with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and was approved by the Institutional Animal Care and Use Committee at Sejong University. Mice were group housed under a 12:12 light-dark lighting schedule with free access to food and water. The temperature in the room was 22°C. Twelve- to sixteen-week-old male C57BL/6 mice were injected intraperitoneally with sterile PBS or amitriptyline twice a week for 4 weeks. Body weight was measured before every injection. The injected mice were subjected to behavioral tests one week after the last injection.
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Measurement Of Atp Level
Cellular ATP levels were measured using the luminescence ATP detection assay system . The cells were incubated with or without chemicals for various time points, 100 l of the ATPlite 1step reagent was added to the wells, and the cell plates were orbitally shaken for 3 min. The plates were read for emitted luminescence using a microplate luminometer .
Animal And Cell Research
No clinical evidence supports the use of amitriptyline for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
In rat models of Parkinsonâs disease, amitriptyline decreased the loss of dopamine-sensitive neurons. It also protected neurons with tyrosine hydroxylase activity, which are decreased in patients with Parkinsonâs disease .
The drug also increased dopamine levels and improved movement in rats with Parkinsonâs-like disease .
In cell studies, amitriptyline decreased the release of inflammatory agents from mast cells by up to 98% .
Amitriptyline decreased gut and kidney inflammation in rats .
Brain Health and Repair
In rat studies, amitriptyline increased BDNF in rats with Alzheimerâs disease, which increased both their short and long-term memory .
Similarly, amitriptyline increased GDNF levels in brain cells. Increasing GDNF may improve neuron survival and protect neurons against stress .
Amitriptyline improved cognitive function and decreased stress in aged rats .
It slightly improved cognitive function in depressed rats .
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Mixing Amitriptyline With Herbal Remedies And Supplements
Do not take St John’s wort, a herbal remedy often taken for depression, while you are being treated with amitriptyline. It will increase your risk of side effects.
Theres very little information about taking amitriptyline with other herbal remedies and supplements. They are not tested in the same way as medicines.
Ami Hydrochloride Protects Nigral Da Neurons
Estimated total population counts revealed a significant sparing =7.729, p=0.0028) of THir neurons in the SNpc of rats that received chronic AMI treatment compared with saline control rats measured at 4 weeks following 6-OHDA .
Chronic amitriptyline treatment prevents dopamine neuron loss. Rats treated chronically with saline had a substantial loss of tyrosine hydroxylase immunoreactive neurons in the SN compared with rats treated with AMI . Stereological assessment revealed a significant sparing of THir neurons in the substantia nigra pars compacta of rats that received chronic AMI treatment compared with saline control animals . To ensure that AMI prevented THir neuron loss and not simply a downregulation of the TH phenotype, we quantified both NeuNir/nonTH and NeuNir/THir neurons in the SNpc ipsilateral to 6-OHDA injection . Results indicate both populations of cells declined in comparable numbers, but overall there was less cell death in AMI treated animals . This is consistent with AMI promoting cell survival, not merely preservation of phenotype. Graph represents mean±SEM *p< 0.05, **p< 0.01. Scale bar=250M.
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Are There Any Warnings About Taking Amitriptyline For Sleep
Until your body gets used to the medicine, be careful with any activities that require you to be alert like driving or operating machinery.
You should not drink alcohol or take other medicines that can make you drowsy with amitriptyline because it can increase the effect of the drug.
You should not suddenly stop taking amitriptyline. Talk to your doctor about the best way to gradually stop this medicine.
Are There Side Effects From Taking Amitriptyline For Sleep
Amitriptyline can have some serious side effects. Before taking the medicine, be sure to let your doctor know if you have ever had an allergic reaction to amitriptyline or other drugs, or if you have ever had suicidal thoughts or behavior.
Let your doctor know if you have:
- heart disease, liver, or kidney problems
- glaucoma, as amitriptyline can increase the pressure in your eye
- diabetes, as amitriptyline can affect your sugar levels, so you may need to check your sugar more often when you start taking amitriptyline
- epilepsy, as amitriptyline can increase the risk of seizures
Talk to your doctor if you are pregnant or breastfeeding. Research has not made clear for certain whether amitriptyline is safe to use during pregnancy or if you are breastfeeding.
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Approaches To Pain Assessment
When assessing pain in patients with PD, using a validated pain scale that targets symptoms specific to PD whenever possible will more accurately categorize pain type. The first pain tool designed specifically for patients with PD is the Kings PD Pain Scale .4,12 This scale has 14 questions that measure severity and frequency of different types of pain specific to PD. A complementary patient screening tool, the Kings College PD Pain Questionnaire , is designed for assessing whether or not specific pain types are present. All questions on the KPPQ correspond with a specific question on the KPPS. Screening patients with the KPPQ can facilitate identifying pain types that correspond to the KPPS assessment tool.
If unable to assess pain with scales specific to PD, validated general pain scales, such as the Likert scale, can be utilized to determine quality and severity of any type of pain.18 Using PD-specific pain scales may better characterize a patients pain symptoms, however, which may lead to more targeted treatment options.
What Should I Do If I Forget A Dose
Take the missed dose of the regular tablet, orally disintegrating tablet, extended-release tablet, or extended-release capsule as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
If you are using levodopa and carbidopa enteral infusion and will be disconnecting the infusion pump for a short time , other than the normal nightly disconnection, ask your doctor if you should use an extra dose before you disconnect the pump. If the infusion pump will be disconnected for longer than 2 hours, call your doctor you probably will be advised to take levodopa and carbidopa by mouth while you are not using the suspension.
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What Should I Know About Storage And Disposal Of This Medication
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture .
Store cassettes containing levodopa and carbidopa enteral suspension in the refrigerator in their original carton, protected from light. Do not freeze the suspension.
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA’s Safe Disposal of Medicines website for more information if you do not have access to a take-back program.
It is important to keep all medication out of sight and reach of children as many containers are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location â one that is up and away and out of their sight and reach.
Side Effects Of Mysoline
Mysoline may cause unwanted side effects in the short term however, these side effects diminish with longer use. Side effects of Mysoline may include:
- Difficulty walking
Serious complications with the drug are rare but could include blood cell and bone marrow problems. Your health care provider will check your blood counts every six to 12 months to screen for these problems. Mysoline has a drug interaction with phenobarbital, so the drugs should not be taken together.
Before taking Mysoline, be sure to tell your doctor if you:
In addition, you should avoid alcoholic beverages while taking Mysoline. Do not stop taking the drug suddenly or switch brands without first consulting with your health care provider.
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