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Friday, February 8, 2013

Gut Pain Management: Visceral pain and Gastroparesis

This was shared with me by my friend Freda. I thought it was important enough to put into my blog. The link to the article can be found HERE.



"Gut pain management: Visceral pain and gastroparesis

Excerpts from the presentation by: Robert Twillman, Ph.D. who spoke at the GPDA and ANMS organized consensus meeting on the Treatment of Gastroparesis, held in September 2004 at the Kahler Grand Hotel, Rochester, MN.



Robert Twillman PhD

Pain Management Program Director

University of Kansas Hospital

Clinical Associate Professor of Psychiatry and Behavioral Sciences



University of Kansas School of Medicine



Historically, pain has been a neglected symptom in patients with gastroparesis, even though (and perhaps because) it is often the most problematic to manage. In the most extreme cases, pain can dominate the picture, resulting in considerable suffering and utilization of health care resources. The problem is often compounded by the reluctance of many physicians to recognize the pain as “real”, in part due to the lack of overt evidence of significant inflammation or injury to the stomach. This may lead to dismissal of the pain as a manifestation of “narcotic-seeking behaviour” or to an attribution of purely psychological factors as the root cause of the pain. The end result is often a desperate patient bereft of a long-term relationship with a caring physician.



Much of this problem stems from a complete lack of knowledge about the causes of pain in gastroparesis. There are no experimental studies or clinical trials on this subject. Therefore the approach to treatment is both arbitrary, subject to the biases of the treating physician, and empirical, without any biological rationale to guide therapy.



The approach to pain in these patients begins with an empathetic understanding and recognition that the pain is real. Such an understanding and recognition will usually relieve anxiety in patients and their families, and will promote a trusting relationship between physician and patient.



Possible Causes and Nature of the Pain

Looking through the literature, the problem of chronic pain in gastroparesis is estimated to affect anywhere between 50 and 90 percent of patients. The cause of this pain is not well known. Neuropathic pain, pain generated by damaged or inflamed nerves, is thought to be the primary cause, and is one of the most challenging types of pain to manage. Neuropathic pain is common in idiopathic, as well as in diabetic gastroparetic patients. This type of visceral (abdominal) pain is often described as diffuse, dull, achy and crampy. (Writer's note: Other types of pain described by gastroparetic sufferers may be sharp and localized in areas over the abdomen. The nature of this pain may be more related to muscular spasms within the stomach or small intestine, or related to trapped gas.)



The sensory wiring of the gastrointestinal tract is very complex and bound up with the central nervous system, tying it to emotions and behaviors. This is why pain is a mind, body and spirit phenomenon requiring more than just medications to help control the problem.



We know that sensory nerves within the gut are sensitive to stretching and distention; as well, chronic pain can cause a hypersensitization within the central nervous system to the painful sensations. Also, any regional inflammation, say in the stomach or esophagus, becomes hyperactive, working overtime relaying messages to the brain communicating “pain”. Further compounding the problem, many patients with gastroparesis will describe an acute pain occurring soon after eating, layered on top of their chronic pain. (This acute, sharp pain may be related to spasms occurring in the upper portion of the stomach due to its failure to relax and “accommodate” the just-eaten food. As well, a sluggish emptying of the gall bladder seems to be tied up with poor emptying of the stomach, coupled with uncoordinated muscular action by the small intestine. This may all add to the pain experienced soon after eating).



Where to Begin?

Psychological interventions are helpful measures and should be considered as a part of the pain-management regimen for every patient presenting with gastroparesis-related pain. These interventions avoid the added risks posed by pharmacotherapy, and help promote a sense of control on the part of the individual. Simple techniques such as deep relaxation, cognitive restructuring, and distraction may be helpful, and can easily be taught by most health care providers. Other techniques such as acupuncture, hypnosis, biofeedback require a greater level of expertise on the part of the health care practitioner, but should be utilized whenever available.



The primary health care provider needs to be well versed in the pharmacology of analgesic drugs including narcotics. Even though a pain specialist may be involved in their care, patients with gastroparesis-related pain often rely on their primary physician to provide relief during flare-ups.



(For those who live in small towns and rural areas, finding help for more severe gastroparesis related-pain may be difficult. Try consulting with a cancer pain specialist or palliative care doctor in your town. They can guide you through logical choices for your pain care).



What are the Drug Choices?

A wide variety of drugs are available from the traditional analgesic (pain relief) medications to a number of other unrelated pharmacological groups employed for pain management.



Beginning pharmacological therapy for abdominal pain management should start with the non-steroidal anti-inflammatory (NSAID) medications. Many of these popular drugs are available over the counter while others require a prescription. Some examples are:



diclofenac (Voltaren®, Cataflam®)

diflunisal (Dolobid®)

ibuprofen (Motrin®, Advil®)

indomethacin (Indocin®)

ketoprofen (Orudis®, Oruvail®)

ketorolac (Toradol®)

naproxen (Naprosyn®, Alleve®)

piroxicam (Feldene®)



These medications can be helpful but have the potential to cause stomach ulcers and bleeding. To help counter this problem, the use of stomach acid-suppressing medications may be useful. The newer agents, the COX2 inhibitors, were favored since they don't irritate the stomach lining, yet recently some have been pulled from the market due to an increased risk of strokes and heart attacks.



Antispasmodics may have particular application in treating painful abdominal cramps or sharp, painful spasms occurring soon after eating, but their use is limited in gastroparesis. Antispasmodics have the effect of further slowing down the digestive tract. While not dismissing them outright, some formulations come in rapid and short-acting preparations. Levsin/SL®, for example, can be chewed or placed under the tongue and allowed to dissolve.



The tricyclic anti-depressants (TCA) drugs have become one of the mainstays for treating chronic abdominal pain. Though the FDA has never officially approved them for this application, they have been well researched to establish their effectiveness in pain management. TCAs work best for the burning/searing type of pain common to neuropathic pain syndromes. The TCA drug most studied and prescribed most commonly is amitriptyline (Elavil®). Dosages are started at a very low level, lower than used for treating depression, and then slowly increased. It may take several weeks before benefits of pain reduction are experienced. Low dosages are also important because TCAs can slow the emptying of the stomach and intestines. Other examples of TCAs:



Desipramine (Norpramin®)

Doxepin (Sinequan®)

Imipramine (Tofranil®)

Nortriptyline (Aventyl®, Pamelor®)



Unfortunately, TCAs can cause bothersome side-effects of gastrointestinal distress. Nortriptyline may be the least likely to cause these unwanted problems. Working closely with your doctor and carefully adjusting dosages is essential.



The selective serotonin reuptake inhibitors (SSRIs) have not been clearly proven to be effective tools against neuropathic pain.



Finally, a new category of antidepressant drugs the selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) are showing promise in treating neuropathic pain. Venlafaxine (Effexor) and duloxetine (Cymbalta) are two agents being used. The FDA has recently approved Duloxetine for its use in treating diabetic neuropathic pain.



Anticonvulsant/anti-epileptic drugs have also demonstrated their effectiveness in clinical trials against burning/searing pain of neuropathies. A wide selection of these drugs is also available and can be used in combination with the TCAs to increase overall potency. Examples are:



carbamazepine (Tegratol®)

clonazepam (Klonopin®),

gabapentin (Neurontin®)



Gabapentin (Neurontin®) has become very popular, primarily due to its superior safety profile compared to the other anticonvulsant medications. Gabapentin has relatively few side effects and is well tolerated especially if the dosage is gradually advanced in increasing increments. It has few, if any, drug interactions. It is expensive, but it does not require routine monitoring of blood levels and liver functions tests as is required for Tegratol® surveillance.



Clonidine (Catapres®), an anti-hypertension drug, has also been shown to work for neuropathic pain. Its role, however, may be more limited in treating abdominal pain syndromes since its effectiveness has only been demonstrated through intrathecal administration, and less so transdermally or with orally administered preparations.



The last category of drugs to discuss is the narcotic drugs or “opioids”. The best known is Morphine. Surprisingly, narcotics have not shown to be that effective for neuropathic abdominal pain like that of gastroparesis.



There is an expansive variety of narcotic, and synthetic narcotic drugs available to the physician in treating his patients. Many of these drugs have an undesirable effect of slowing down the gastrointestinal tract thereby worsening the other symptoms of gastroparesis. It is possible to get around these problems of narcotic drug- induced, slowed-gut motility and still provide good pain relief.



Many patients with mild-to-moderate pain symptoms can be managed without graduation to regular narcotic use. However, there remains the individual with severe pain who needs more effective pain control. Even though opioids may not be extremely effective in this condition (in keeping with the possible neuropathic nature of the pain), they are inevitably used for this category of patient, and may have some utility.



This creates at least two major issues: first, the possibility of narcotic dependence and second, the potential risk of slowing gastrointestinal motility and further contributing to worsening of symptoms.



Physical dependence resulting from the chronic use of narcotics to treat pain is an expected outcome, and patients should be cautioned not to discontinue their use without a tapering schedule. Addiction is a much rarer phenomenon, especially in patients without a history of substance abuse. Doctors and patients should understand the distinctions between physical dependence and addiction, and are referred to definitions published by the American Pain Society, American Society of Addiction Medicine, and American Academy of Pain Medicine.



With respect to the problem of constipation, the scientific literature suggests that methadone, fentanyl (Duragesic), and Buprenorphine (Temgesic, Subutex) may be narcotics that produce less constipation than other drugs.



Another drug (a derivative of codeine) called tramadol (Ultram®), may have some promise as a constipation-sparing analgesic for patients with moderate pain.



Additionally, there are a number of studies in the literature looking at treating constipation by using narcotic-blocking agents. These drugs help to block the side effects of narcotics such as constipation, while not diminishing the pain-reducing effects of the prescribed narcotic.



Examples of these narcotic-blocking drugs used along with narcotics are:



naloxone (Narcan®),

Methylnaltrexone (MNTX), and

nalmephene.



Taken at very low doses, and taken orally, they can reverse the negative impact of the narcotic on the GI tract.



What is intrathecal?



What are intrathecal medication delivery systems?



The spinal cord is protected by a tissue covering.



The intrathecal area is the space between this tissue covering and the spinal cord.

Medications can be delivered into this space and bathe the spine with various drugs.



For more severe abdominal pain syndromes, implantable devices have been devised to permit regular drug delivery through a system composed of two implantable components: an infusion pump and an intrathecal catheter. The pump is placed abdominally into a pocket created underneath the skin, while the catheter tip is inserted into the intrathecal space of the spine, then tunneled under the skin and brought to the connection site on the pump. Medication can be delivered through the pump at constant or variable flow rates.



Medtronic manufactures intrathecal drug delivery systems.



Many different types of medications can be infused into the intrathecal space for pain management.





The science of pain control is looking even farther afield to agents like ketamine, a short-acting, general anaesthetic; it can be delivered intra-nasally via a nose spray. Ketamine provides a sense of euphoria and emotional detachment from the pain. Finally, even drugs, such as memantine (Namenda), used for treating Alzheimer's disease are being studied for use in neuropathic pain relief.



Celiac plexus nerve block

Another method used to control chronic abdominal pain is by means of chemically damaging a collection of nerves, called the “celiac plexus”. This is the main nerve branch which communicates pain from the abdomen. Generally, a trial block with a short acting and reversible agent is used before the physician proceeds with permanently destroying the celiac nerve bundle though injection. Complications can occur, so this method is reserved for after all other medical approaches have failed. Published reports show the majority of patients have a good response of pain reduction.

_____________________



On the Horizon:



In Canada, the federal government has recently approved a new cannabis (marijuana)- based drug called Satives. Developed by GW Pharmaceuticals and Bayer, the drug is conveniently administered via a mouth spray. Canada is the first country in the world to approve the drug. Approved for use in treating neuropathic pain of MS, it will help fill the need for more neuropathic pain therapies.





Ocean “cone snails” have a neuro-toxic sting that is providing a new chemical family for enthusiastic research into more effective pain-control medications. Ziconotide, a synthetic form of the cone snail toxin has been recommended for approval by the FDA. Intrathecally administered ziconotide produces pain reduction and has an advantage over intrathecal morphine in that there is no development of tolerance after prolonged use.



Take-home Message:

Often multiple drug therapies may be necessary for controlling more severe pain. Combinations of medications such as the tricyclic antidepressants and anticonvulsants are effective; and occasionally, some individuals will also require narcotic therapy added to this regimen. If pain management fails with these steps, then treatments with implantable systems, such as a spinal cord simulator, or intrathecal pump should then be considered.



The constipating effect, and the slowing of gastric emptying caused by narcotics can be counteracted with low doses of narcotic-blocking agents. This does not diminish the pain- reducing action of the prescribed narcotic.



Regaining Control

Pain and the symptoms of gastroparesis can take their toll on the mind, body and soul greatly diminishing quality of life. Finding effective therapies that help subdue symptoms makes everyday coping much easier. Connecting with an empathetic physician and psychologist/psychiatrist to work with you is your best option.





Just trying to keep everything in balance and manageable is a daily struggle. Here are some tips:



Connect with a supportive community.

Find spiritual strength through meditation or prayer.

You are not to blame for your pain.

Stress and emotions just modify your experience of pain, they do not cause the pain.

Seek professional help.

Good pain-management is your right. Find a doctor willing to work with you.

Have an advocate willing to go with you to your medical appointments.

Keep a journal.

Make connections with nature and/or pets."


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