Wednesday, 3 September 2014

ClinicSpeak: pregabalin for pain

Have you got pain? This post may help. #ClinicSpeak #MSBlog #MSResearch

"Pain is a big problem for MSers, particularly for those of you with spinal cord disease. We refer to this type of pain as myelopathic pain. Some MSers describe the pain as have two qualities. Firstly, a continuous gnawing, toothachy, type of pain that waxes and wanes and interferes with daily activities and sleep. Secondly, some MSers describe sudden electric-shock-like pain that is superimposed on the background pain; these short sharp bursts of pain are often accompanied by positive sensory symptoms, for example pins-and-needles, buzzing, burning, itching or prickling sensations to name a few adjectives. It is important to delineate these two pains from each other as they tend to respond to different treatment strategies. The sharp shooting pains are due to abnormal spontaneous firing of demyelinated, or poorly remyelinated, nerve fibres in sensory pathways of the spinal cord; this pain tends to respond to drugs that block sodium channels, for example lamotrigine, phenytoin, carbamazepine and oxcarbazepine. Gabapentin and pregabalin may work for these pains, but as they are not sodium channel blockers they are not as effective as the other agents. In comparison gabapentin and pregabalin are much better at suppressing, or at least relieving, the background gnawing pain. The study below confirms this for pregabalin. In my experience gabapentin and pregabalin often work better when prescribed in combination with a low dose of a tricyclic antidepressant, for example amitriptyline. I tend to use a very low dose of  amitriptyline at night starting at 10mg at night and increasing the dose very gradually by 10-mg every 1-2 weeks until patients have an adequate therapeutic response or can't tolerate the drug due to side effects. The most common side effects on amitriptyline are dryness of the mouth, constipation, blurred vision, urinary hesitancy, weight gain, worsening cognition and sedation with a hang-over effect. The sedative component of amitriptyline is what makes the drug such a good choice for central pain syndromes; it helps patients get a good nights sleep. Interestingly, because it has mild anticholinergic effects it may improve urinary frequency and urgency at night and this may also improve sleep. The hang-over effect of amitriptyline is dose related and  typically wears off after 1-2 weeks. If you don't respond to amitriptyline there are other tricyclic antidepressants that may help or a new atypical antidepressant duloxetine that seems to be particularly effective in central pain syndromes."

"Please note that often powerful opiod drugs are prescribed for central pain syndromes, these rarely help myelopathic pain and can paradoxically make it worse. Similarly, non-steroidal anti-inflammatory drugs rarely work in central pain syndromes, but many patients find them helpful. I suspect a response to an NSAID indicates a peripheral musculoskeletal contribution to the pain."

"If the pain does not respond to pharmacological manipulation, it may be worthwhile being referred into the pain service to try add-on alternative non-medical therapies for pain, for example acupuncture, TENS (transcutaneous nerve stimulation), central nerve stimulators, CBT (cognitive behavioural therapy) and other biofeedback techniques."

"If you have pain and it is there all the time you need to be treated. Pain often starts a vicious cycle whereby it lowers mood and may contribute to the development of depression, depression lowers your central pain threshold that makes the pain worse. Therefore chronic pain and depression often coexist and need to be treated together. This is why anti-depressants, and CBT, are commonly used as part of a cocktail to manage MS-related pain."


"Please feel free to share your experiences of your pain management and to ask questions."

Onouchi et al An open-label, long-term study examining the safety and tolerability of pregabalin in patients with central neuropathic pain. J Pain Res. 2014 Jul 28;7:439-447. eCollection 2014.

PURPOSE: Studies of pregabalin for the treatment of central neuropathic pain have been limited to double-blind trials of 4-17 weeks in duration. The purpose of this study was to assess the long-term safety and tolerability of pregabalin in patients with central neuropathic pain. The efficacy of pregabalin was also assessed as a secondary measure.

PATIENTS AND METHODS: This was a 53-week, multicenter, open-label trial of pregabalin (150-600 mg/day) in patients with central neuropathic pain due to spinal cord injury, multiple sclerosis, or cerebral stroke.

RESULTS: A total of 103 patients received pregabalin (post-stroke =60; spinal cord injury =38; and multiple sclerosis =5). A majority of patients (87.4%) experienced one or more treatment-related adverse events, most commonly somnolence, weight gain, dizziness, or peripheral oedema. The adverse event profile was similar to that seen in other indications of pregabalin. Most treatment-related adverse events were mild (89.1%) or moderate (9.2%) in intensity. Pregabalin treatment improved total score, sensory pain, affective pain, visual analog scale (VAS), and present pain intensity scores on the Short-Form McGill Pain Questionnaire (SF-MPQ) and ten-item modified Brief Pain Inventory (mBPI-10) total score at endpoint compared with baseline. Improvements in SF-MPQ VAS and mBPI-10 total scores were evident in all patient subpopulations. Mean changes from baseline in SF-MPQ VAS and mBPI-10 scores at endpoint were -20.1 and -1.4, respectively.

CONCLUSION: These findings demonstrate that pregabalin is generally well tolerated and provides sustained efficacy over a 53-week treatment period in patients with chronic central neuropathic pain.

3 comments:

  1. Prof G, I have early MS. Is it inevitable that I will develop pain? The thought of having to live with pain worries me a lot.

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  2. Re: "Prof G, I have early MS. Is it inevitable that I will develop pain? The thought of having to live with pain worries me a lot."

    Please see following post: http://multiple-sclerosis-research.blogspot.co.uk/2014/09/clinicspeak-preventing-ms-related-pain.html

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  3. My experience echoes many of the points in your post.

    Spinal cord damage means I've had myelopathic pain from early on in my MS journey. Thankfully my GP, MS nurses and neurologist were all really helpful in getting me onto symptom-relieving treatments (both pharmaceutical and a short course of acupuncture) that we've tweaked as necessary over the past six years.

    The pain never goes away completely but the meds keep it in the background and the combination of gabapentin and night-time amitriptyline helps me get good quality sleep which enables me to carry on working / getting on with my life.

    In a relapse I often get an increase in pain and, following advice from a pain management clinic, take NSAIDs for a few days which seem to help.

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