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7 Articles in Volume 5, Issue #5
Effective Non-Drug Treatment of Depression
First Line Treatment of Musculoskeletal and Neuropathic Pain
Pain Drug Use Policy
Targeted Peripheral Analgesics in Chronic Pain Syndromes
Therapeutic Drug Monitoring
Tiredness and Chronic Pain Management
TMD/Facial Pain and Forward Head Posture

First Line Treatment of Musculoskeletal and Neuropathic Pain

Initial treatment of musculoskeletal and neuropathic pain can be more effective by incorporating combination pharmacologic alternatives as adjuncts to oral or parenteral analgesic medication.

This article was supported by a grant from Winston Laboratories, Inc., Vernon Hills, Illinois.

The new concerns raised about the safety of nonsteroidal anti-inflammatory agents (NSAIDs) has led to physicians rethinking treatment of both acute and chronic musculoskeletal pain.1,2,3 Combination pharmacologic approaches abound with analgesics, muscle relaxants, anti-depressants, sedative hypnotics, anxiolytics, topical agents and anticonvulsants offering viable alternative options. Establishing a rationale for treatment — based on diagnostic evaluation and advantages of certain types of treatment for selected patients — is essential for all clinicians evaluating and treating patients for their pain problems. Many alternatives may be utilized as adjuncts to analgesic medications with the alternative choices offering added benefits without the risk of diversion and abuse seen with opioid therapy.4,5

Diagnostic Considerations

History of pain onset and precipitators facilitates more judicious use of diagnostic tests.Recumbent or nocturnal back pain must be taken more seriously regarding possible underlying malignancy or neurogenic claudication. Pain without antecedent trauma history makes one look for a disease process as an etiology for the pain complaints.

Physical examination to detect localized tenderness, swelling, spasm or neurologic deficit offers great value in deciding the need for X-ray, MRI, CT or other imaging studies. Electrodiagnostic evaluation often is helpful in those individuals with neurologic involvement associated with pain complaints. Such testing can include electromyography (EMG), nerve conduction velocity (NCV), or somatosensory evoked potentials (SSEP).

The patients who should be started on nonsteroidal anti-inflammatory drugs for their pain are those with obvious swelling, inflammation, or those who suffered an acute injury or have a known inflammatory disease process. A logical extension of this reasoning means that many with neck or back pain complaints and those with chronic peripheral pain should not be taking NSAIDs and can thus avoid the expense and morbidity which is associated with their use.

Treatment with Nonsteroidal Anti-Inflammatory Agents

Individuals who need NSAIDs should not be randomly given a particular NSAID nor should all patients be started on the same NSAID. While cost and formulary issues may be important, there should be additional factors in picking the right drug for a particular patient.

Selective COX-2 inhibiting NSAIDs were thought to be the drug of choice because of indications of lessened gastrointestinal bleeding complications until recent studies raised concerns about cardiac side effects in Vioxx®, Bextra® and Celebrex® users.1,2,3 Significant serious reactions such as Stevens-Johnson syndrome also played a role in the recent withdrawal of Bextra by Pfizer,6 following the earlier voluntary withdrawal of Vioxx by Merck amid reports of increased risk of heart attacks and strokes.7

Despite much publicity about concerns for users of these drugs, a recent FDA Advisory Panel still recommended, by a 31 to 1 vote, to keep Celebrex on the market and, by narrow margins, recommended continued availability of both Vioxx and Bextra with appropriate warnings.8 Celebrex can still be safely prescribed to those who are not allergic to sulfa drugs and who limit chronic use to 200mg daily, a dosage that appears to be safe and without any increased cardiac risk. It still might be used for stiffness and swelling associated with pain, particularly in those who might be unable to tolerate other NSAIDs, including many elderly patients, those with increased gastrointestinal bleeding risk, or those on concomitant anticoagulant therapy.

The long-term safety of other newer NSAIDs is not yet known. Studies have yet to be done confirming the lack of potential cardiac concerns for Mobic. Even some older NSAIDs and those sold over the counter need to be monitored as more is learned about cardiac disease factor risks. Patients using prophylactic low dose aspirin also must be advised regarding the potential interference of agents such as ibuprofen with the anti-platelet function of the low dose aspirin.

Treatment with Muscle Relaxants

Outcome-based assessment of acute neck and back pain treatment clearly shows benefit with muscle relaxants and can shorten recovery by around two days.9 Recent reports indicate the lack of additive benefit through combination of ibuprofen with an effective dose of cyclobenzaprine, further strengthening the argument against addition of NSAIDs for acute neck and back pain.10

Soma10 should generally be avoided for new muscle relaxant prescriptions. It is metabolized to meprobamate, is habit forming, and has abuse potential with value as a street drug.

Pill splitting does not offer a convincing reason for selection of generic cyclobenzaprine at a 10mg dose versus the brand name 5mg dose. There is a lowered sedation and lowered discontinuation rate with similar efficacy using the 5mg dose.9 Splitting the 10 mg pills in an effort to match the efficacy and side effect profile of the brand name cyclobenzaprine11 may unfortunately result in varying dose levels which may be less than the effective dose or high enough to increase side effects leading to possible discontinuation of the drug prior to achieving treatment goals.

Cost may preclude selection of Skelaxin.10 While it may offer some benefit by providing sedation although its efficacy, relaxing muscles has not been clearly demonstrated.

Antidepressant, Sedative Hypnotic and Anxiolytic Use

A key question to ask a pain patient is whether they have problems falling or staying asleep. For those with difficulty falling asleep, use of a benzodiazepine or sedative hypnotic sleep aid is appropriate. For those with early morning awakening, additional questions should address possible depression associated with pain that might merit use of an antidepressant medication. For those with neuropathic pain,12 many physicians now favor amitryptiline or nortryptoline — with the latter having less side effects for many.

The newer antidepressant duloxetine (Cymbalta®)14 would appear to be the agent of choice in a diabetic with neurogenic pain. Many physicians are now attempting to assess if the unique benefit of reduction in nerve pain seen in diabetics will generalize to helping a variety of other painful neuropathic conditions beyond the current FDA-approved product indications.

Topical Treatment of Pain

Topical capsaicin15 has been approved for some time as an over the counter treatment for arthritic and neuropathic pain, including post herpetic neuralgia and painful peripheral nerve conditions. A newer triple strength formulation called Axsain® is now available which combines 0.25% capsaicin with a lidocaine vehicle.16 The increased strength of the capsaicin should improve the substance P mediated therapeutic response to the capsaicin compared with earlier preparations, while the lidocaine offers a benefit in improving patient tolerance of the transient burning sensation associated with use of this new topical preparation. Patients should be counseled that burning and stinging sensations may occur at the site of application, but will generally disappear or diminish in 3-5 days with continued use. Anecdotal reports of dabbing the treated areas with a wash cloth soaked in milk also seem to improve patient tolerance to allow not only the 21% pain reduction expected over the first week but also the greater response seen over the six week trial period needed to achieve full effectiveness.

Topical lidocaine patches have also been approved for use in treatment of post-herpetic neuralgia.17 Recent reports also suggest that these patches may offer benefit relieving knee pain in osteoarthritis as well as offering pain reduction in the treatment of back pain.18,19 Its mechanism of action involves blocking porous sodium channels around nerve endings and lessening pain. A functional MRI case report20 also indicated some central effects mitigating thalamic pain recognition.

Anticonvulsant Treatment of Pain

Gabapentin (neurontin) has been FDA-approved only for post herpetic neuralgia pain.13,17 While many have attempted it's use for a variety of other pain problems, it has limitations including the need to slowly titrate the dose to usual therapeutic levels, and it can cause swelling as well as sedation. It also requires a TID dosing regimen. Pain specialists are eagerly awaiting the arrival of pregabalin (Lyrica) perhaps as early as later this year. It has shown promise in treating not only post herpetic neuralgia but also painful diabetic neuropathy with action similar to gabapentin. It requires a BID dose for some indications but it can be initiated at the suggested therapeutic dosage for others.


First line treatment of musculoskeletal and neurogenic pain demands some effort at obtaining a history, performing a physical examination, and selecting appropriate diagnostic tests prior to initiating treatment for pain. Treatment measures for pain should include NSAIDs only for specific patients and one can still safely prescribe the sole remaining selective cox-2 NSAID for the appropriate patient. Preference should be given for certain muscle relaxants, antidepressants, topical agents and anticonvulsants based on product characteristics, patient response, and side effects.

“Many physicians are now attempting to assess if the unique benefit of reduction in nerve pain seen in diabetics will generalize to helping a variety of other painful neuropathic conditions beyond the current FDA-approved product indications.”
Last updated on: May 16, 2011
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