Chronic Non-Malignant Pain And Its Side Effects

Q: What is chronic non-malignant pain [CNMP]?

A: Nonmalignant, chronic pain (>6 months) is due to remodeling within the central nervous system. This central neural plasticity results in persistent pain even after correction of pathology. It is characterized by allodynia, hyperalgesia, and/or the spread of pain to areas beyond the area involved with the initial pathology.

Q: I understand that CNMP is not a specific medical diagnosis, so why use it in describing a group of patients?

A: Yes, it is not a diagnosis, but when you use this term, it implies a serious disability and a level of severity that is high enough to require more than simple treatment. Often the treatment involves a combination of non-pharmacologic interventions and pharmacologic treatment. Another implication associated with the term CNMP is that opioid therapy may be needed and the pain problem is not resolving with time and may be neuropathic!

Q: What is the difference between nociceptive pain and neuopathic pain?

A: The basic difference is that if the cause of the pain is removed, the pain will stop in nociceptive pain. For neuropathic pain, there are changes that occur both peripherally and centrally that cause the nervous system to stay activated and with time the pain does not go away, but may actually get worse.

Q: How do you decide if the patient has a CNMP?

A: As CNMP is not a medical diagnosis it is hard. Essentially, when you use the term CNMP you are saying the pain is long-lasting, probably neuropathic in nature and the usual and customary causes of pain (e.g. infection, fractures, traumatic injury) are not present. To do this you must follow the following steps:

1. Confirmation of Diagnosis
2. Get all past records
3. If possible, communicate with the patients doctors so that all are in agreement with your diagnosis and approach
4. If needed, get a second opinion by another pain specialist

Q: In addition to sensitizing the nerves in the periphery and more centrally, pain has the side effect of changing the patient’s brain and inducing pain-related behaviors that might require treatment. When do you pursue behavioral interventions to support your pharmacologic and non-pharmacologic interventional therapies?

A: If you see a chronic pain patient, the decision to recommend behavioral therapy and/or use psychoactive medications (e.g. SSRI’s) is best done after consultation with a pain-trained psychotherapist or psychiatrist.

Q: How do you normally record pain?

A: There are two common ways to record pain. First is the VAS pain scale (see below) where you give the patient a sheet of paper with a 100 mm long line on the paper. You ask the patient to draw a vertical slash on the line indicating their level of pain. The other method is to ask the patient to give you a number from 0-10 to rate pain.

Q: Obviously with severe disabling pain, there are many ways of treating it, so which one is best?

A: The decision on which method (see first table below for list of treatments) is best is complex and involves multiple factors (see second table below).

Which Treatment Approach to Take?

► Behavioral Assessment and Treatment
► Sodium Channel Blocking Medications
► Mild Anticonvulsant Medications
► Tricyclic antidepressants
► Non-Opioid Analgesics
► Atypical antidepressants
► Nerve Injections & Counter Stimulation Therapy
► Moderate and Strong Opioids
► Moderate-Strong Anticonvulsant Medications
► Benzodiazepines
► SSRI’s

Factors affecting the decision on which treatment is best to use:

1. Diagnosis
2. Other illnesses & age, stability, weight
3. Attitude and medication use profile
4. NNT (ARR); NNH (to withdrawal)
5. Side Effects; ADRnx; Toxicity Risk;
6. CYP450
7. FDA approval status
8. Cost of medication

Q: What are the most common diagnoses that are associated with chronic non-malignant pain?

A: There are many, many diagnoses that are likely to turn neuropathic and produce a chronic pain state.

Q: What are the most common other medical issues that are associated with a CNMP?

A: There are many, many medical diseases that affect what treatment you should use on a CNMP patient.

Q: When considering which pharmacologic therapy to prescribe, you must consider the NNT and NNH of medications. Tell me more about both NNT and NNH?

A: NNT50% is the number of patients you need to treat with the treatment to get at least 1 patient 50% better. Obviously, a low number is good and a high number is bad here. NNH(w) is the number of patients you treat with the treatment before one patient quits prematurely either because of side effects or ineffectiveness of the treatment. Here the better number is high and the worse number is low. These two numbers help you compare medications for relative efficacy. They are typically calculated from a randomized blinded controlled clinical trials to help rate and compare drugs [1] [2].

The characteristic of a good medication is one that has a low NNT and a high NNH. Several meta-analyses of medication trials have reported these two numbers for medications commonly used in the management of neuropathic pain.[3][4][5][6][7][8][9][10]

Using the above meta-analysis information, plus the NNT and NNH calculations, this paper has ranked neuropathic suppressing medications as 1st, 2nd, 3rd or 4th line medications.

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Q: When considering which pharmacologic therapy to prescribe, you must also consider the FDA status of a medication. Tell me more about both On and Off label issues in pain medication?

A: The FDA approves medications for a specific population and purpose and the manufacturer can then advertise the drug for the approved purpose and there is an official FDA-approved drug handout which explains what the drug is approved for. This is ON-LABEL. When a drug is used for a disease or on a population (e.g. children) and it was not tested or approved for this is considered OFF-LABEL use and you must inform the patient of this.

Q: Tell me more about the common side effects of pain medication?

A: When considering which pharmacologic therapy to prescribe, you must also consider the common side effects and adverse drug reactions of the medication as the patient may already be experiencing them from another drug of their specific medical status makes a normally tolerated side effect much more problematic. For example, an elderly patient who is prone to falling may not do well on a drug that sedates them even more.

Q: Tell me more about the issue of Drug-Drug interactions and pain medication?

A: When considering which pharmacologic therapy to prescribe, you must also consider the DDIs since DDI-related adverse drug reactions can occur between what you are going to prescribe and what the patient is taking already.

Q: In some cases, you may elect to use a NSAID rather than a NOA (acetaminophen). What are the risks and benefits of this choice?

A: When the pain is due to a traumatic injury or surgical trauma or a flare-up of an arthritic process and you suspect an inflammatory chemical as the pain source, NSAIDs are preferred. When the patient cannot take NSAIDs because of possible G.I. complications or they are very elderly, the first choice is a non-opioid analgesic such as acetaminophen. In all cases, you must consider the odds for gastrointestinal complications with NSAIDs by age and by sex.

Q: When you have a nocebo responsive, pharmacophobic or even some medically complex cases who have a high-pharmacoreactive profile and who can’t or won’t use any prescription medications what do you do now?

A: In such cases, some of these patients can use still use topical medications, others will only use herbal medications or nutraceuticals and some will only use alternative “non-pharmacologic” type therapies. With such cases you have to decide if they can be helped with such alternative methods and non-use of medication will not be put them at great risk.

Now, let’s add this category of patients [Comlex Medical and Pharmacophobics] to our algorithm with another box in the top row at the left of the diagram. Beneath this category of the patient for a first-line therapy box we will also suggest using topical agents and nutraceuticals. Topical medications are applied to the focal pain site using a tissue covering oral stent as a holding device. The most common topical anesthetic medication is benzocaine 20% in orobase® paste or EMLA cream. This medication can be used to control the patient’s pain. Beneath the 1st line therapy box we will add a 2nd line therapy box that suggests using injection and counterstimulation therapies.

Q: Are topical NSAIDs helpful?

A: Many doctors remain skeptical about the efficacy of topical NSAIDs for chronic pain. This may not be correct. Published RCTs on chronic pain conditions (mainly knee osteoarthritis) studied over 800 subjects treated with topical NSAIDs and 322 subjects who received placebo. The analgesic response for combined placebo treatment was 30%, and for combined topical non-steroidal anti-inflammatory preparations it was 63% (NNT was 3.2 (range 2.6 – 4.1).

Q: Are nutraceuticals for Pain helpful?

A: They can be in certain patients, but unfortunately, the data on most herbal medications, supplements and nutraceuticals is weak or non-existent.

Q: Are injections and/or counter stimulation methods for pain helpful?

A: Transiently helpful at best. The two most commonly used injections are trigger point injections for myofascial pain and corticosteroid injections for joint pain and arthritis. Counter stimulation methods commonly used are TENS and acupuncture. In both cases, the data is not robust but still recommended.

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Sources:

1. Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect. BMJ 1995;310:452–4.
2. McQuay HJ, Tramer M, Nye BA, Carroll D, Wiffen PJ, Moore RA. A systematic review of antidepressants in neuropathic pain. Pain 1996;68: 217–27.
3. Rowbotham MC, Petersen KL: Anticonvulsants and local anesthetic drugs, in Loeser JD (ed): Bonica’s Management of Pain, ed 3. Philadelphia, Lippincott Williams and Wilkins, 2001, p 1727.
4. Max MB, Gilron IH: Antidepressants, muscle relaxants, and N-methyl-D-aspartate receptor antagonists, in Loeser JD (ed): Bonica’s Management of Pain, ed 3. Philadelphia, Lippincott Williams and Wilkins, 2001, p 1710.
5. Schechter NL, Berde CA, Yaster M (eds): Pain in Infants, Children, and Adolescents. Baltimore, Williams and Wilkins, 1993.
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8. Galer BS, Jensen MP, Ma T, Davies PS, Rowbotham MC. The lidocaine patch 5% effectively treats all neuropathic pain qualities: results of a randomized, double-blind, vehicle-controlled, 3-week efficacy study with use of the neuropathic pain scale. Clin J Pain. 2002 Sep-Oct;18(5):297-301.
9. Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain 2005;116:109–18.
10. Freynhagen R, Strojek K, Griesing T, Whalen E, Balkenohl M. Efficacy of Pregabalin in neuropatnic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens. Pain 2005;115:254–63.