eMedicine Specialties > Rheumatology > Soft Tissue and Regional Rheumatic Disease

Nonarticular Rheumatism/Regional Pain Syndrome: Treatment & Medication

Author: Daniel Muller, MD, PhD, Department of Internal Medicine, Section of Rheumatology, Associate Professor, University of Wisconsin at Madison
Contributor Information and Disclosures

Updated: Nov 5, 2007

Treatment

Medical Care

  • Fibromyalgia and multiple bursitis-tendonitis syndrome
    • Sedating antidepressant (tricyclic) at night
    • Activating antidepressant in the morning
    • Low-level aerobic exercise and physical therapy, including heat or ice
    • Meditation training (Mindfulness meditation is recommended.)
    • Subcutaneous tender-point injections
    • EMG biofeedback and hypnotherapy
    • Psychotherapy and stress management
    • Cognitive behavior therapy program
  • Regional and local bursitis and tendonitis
    • Acute exacerbations, first 24-48 hours
      • Rest
      • Immobilization
      • Ice
      • Nonsteroidal anti-inflammatory drugs (NSAIDs)
      • Physical therapy
      • Antibiotics for infection
      • Chronic pain treatment
      • Local heat
      • NSAIDs
      • Tennis elbow strap for lateral epicondylitis
      • Padding for bursa and Achilles tendon
      • Local injection of bursa or tendon with lidocaine and long-acting steroids for cases resistant to conservative therapy: Infection must be ruled out prior to the use of steroids, especially in patients with olecranon and prepatellar bursitis. Never inject into the Achilles tendon because of the risk of rupture.
      • Bursal aspiration and sometimes sclerosis with tetracycline
      • Assessment of home and workplace habits such as posture and repetitive motion
  • Alterations in sleep position may benefit persons with neurovascular entrapment such as thoracic outlet syndrome (ie, avoiding arm hyperabduction) and carpal tunnel syndromes (avoiding wrist flexion). Women with heavy pendulous breasts may need brassieres with proper support. Exercises to correct postural deficits are necessary. Night wrist splints may be curative in carpal tunnel syndrome. Postural therapies such as Alexander or Feldenkrais might be beneficial.
  • Proper foot support and orthotics can benefit persons with tarsal tunnel syndrome. NSAIDS can be tried for carpal and tarsal tunnel syndromes. Local long-acting steroid injection can be helpful in carpal and tarsal tunnel syndromes.

Surgical Care

  • No surgical care is necessary for fibromyalgia or multiple bursitis-tendonitis syndrome.
  • Chronic local bursitis and tendonitis occasionally require bursectomy or excision of the inflamed tissue around the tendon, respectively, if conservative measures fail.
  • Carpal and tarsal tunnel syndromes may require surgical decompression. Aggressively treat coexisting carpal tunnel syndrome before surgical therapy for thoracic outlet syndrome.

Consultations

  • Fibromyalgia or multiple bursitis-tendonitis syndrome - Rheumatologist, psychologist, physical therapist, acupuncturist
  • Local bursitis and tendonitis - Rheumatologist, general/orthopedic surgeon, podiatrist, acupuncturist
  • Long-term management of fibromyalgia – Usually, primary care physician

Diet

No known benefits or worsening of symptoms are associated with dietary manipulations. No special diet requirements exist.

Activity

  • Fibromyalgia and multiple bursitis-tendonitis syndrome
    • Often, patients must have periods of rest alternating with mild-to-moderate aerobic activity to optimize function. Hoffman recently published a detailed program of graded exercise for fibromyalgia.5  
    • Moderate activity over baseline often results in increased pain and fatigue.
  • Local bursitis and tendonitis
    • Rest or immobilization for acute exacerbations
    • Moderate muscle strengthening and stretching for chronic syndromes

Medication

Fibromyalgia and multiple bursitis-tendonitis syndrome

Nonrestorative sleep is a significant problem for patients with fibromyalgia. Initial drug therapy consists of a low-dose sedating tricyclic antidepressant (TCA), usually amitriptyline (5-10 mg) 1 hour prior to bedtime.6 The dose is titrated upward every 5-14 days as tolerated, using the minimal dose to achieve restorative sleep. TCAs can cause excessive sedation; therefore, sertraline 25 mg in the morning or another of the more activating antidepressants (eg, fluoxetine) can be added. Other less-sedating TCAs can be substituted for amitriptyline in the evening (eg, nortriptyline) if necessary because of sedation. Dual-action serotonin and norepinephrine reuptake inhibitors, such as milnacipran (not yet on the market) and duloxetine (Cymbalta), have shown to be helpful in fibromyalgia.7,8

Gabapentin has been used off-label for fibromyalgia syndrome because of its salutary effects on chronic pain. A recent clinical trial has shown benefit in fibromyalgia.9 Pregabalin, a similar drug, has been shown to be modestly beneficial in patients with fibromyalgia syndrome at a dose of 450 mg/day.10  

Trazodone can also be particularly helpful for sedation at night and may cause fewer adverse effects than amitriptyline. Doxepin, a non-TCA antidepressant, can be useful in liquid form to titrate at low doses (2-5 mg) for sedation at night. Cyclobenzaprine can relax muscles and can be used as a single dose at night (2.5-10 mg) or, commonly, at 10 mg tid.

Analgesic effects of NSAIDs may be helpful. One controlled trial showed benefits with tramadol (50-400 mg in divided doses)11 ; however, tramadol used in combination with antidepressants can cause serotonin syndrome and increased sedation. Tramadol may play a role by allowing a 4-week drug holiday from antidepressant therapy to reset neural receptors and, in intermittent therapy, for exacerbations. Avoid long-term use of benzodiazepines and narcotics.

Regional and local bursitis and tendonitis

NSAIDs can decrease inflammation. Corticosteroid infiltrations may provide short-term and, occasionally, long-term benefit.  The Achilles tendon sheath must not be injected with corticosteroids because of the risk of tendon rupture. Patients with septic bursitis or tendonitis and systemic symptoms should be admitted for intravenous antibiotic therapy. 

See Temporomandibular Joint Syndrome, Carpal Tunnel Syndrome, Thoracic Outlet Syndrome, Tendonitis, and Bursitis.

Antidepressants

Some antidepressants provide sedation and relieve chronic pain. They may have a moderate-to-marked sedative effect.


Amitriptyline (Elavil)

Analgesic for certain chronic and neuropathic pain.

Adult

5-100 mg PO qhs

Pediatric

Children: 0.1 mg/kg PO qhs, increase as tolerated over 2-3 wk to 0.5-2 mg PO qhs
Adolescents: 25-50 mg/d PO in divided doses, increase as tolerated to 100 mg/d PO in divided doses

Increased sedation with CNS depressants (eg, alcohol, hypnotics, sedatives); effect decreased by carbamazepine, phenobarbital, and rifampin; inhibits antihypertensive response to bethanidine, clonidine, debrisoquin, guanadrel, guanethidine, and guanfacine; increases risk of malignant arrhythmias; enhances hypertensive crisis due to abrupt discontinuation of clonidine; use with altretamine may cause orthostatic hypertension; use with MAOI may induce hyperpyrexia, hypertension, tachycardia, confusion, seizures, and death; increased PT with warfarin; metabolism decreased by SSRIs, cimetidine, and methylphenidate; additive anticholinergic effects with other anticholinergics; lithium increases risk of nephrotoxicity; phenothiazines increase concentration of some TCAs; TCAs may increase concentration of phenothiazines
Enhances hypoglycemic effects of tolazamide, chlorpropamide, and insulin; absorption is reduced by cholestyramine and colestipol; enhances effects of amphetamines; diltiazem and verapamil appear to decrease metabolism of imipramine and potentially other TCAs; enhances pressor response to epinephrine, norepinephrine, and phenylephrine; indinavir and ritonavir may inhibit metabolism of clomipramine and potentially other TCAs; beta agonists predispose patient to cardiac arrhythmias

Documented hypersensitivity; administration within 14 d of MAOI use; narrow-angle glaucoma; pregnancy; lactation

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Anticholinergic adverse effects include dry mouth, flushing, diaphoresis, blurred vision, constipation, tachycardia, and hypotension; avoid abrupt discontinuation of long-term high-dose therapy; caution in hyperthyroidism and renal/hepatic impairment


Sertraline (Zoloft)

SSRI, less sedating than TCAs but appears to improve pain symptoms.

Adult

25-100 mg PO qam

Pediatric

Not established

All SSRIs are capable of inhibiting metabolism of desipramine, dextromethorphan, encainide, haloperidol, imipramine, metoprolol, perphenazine, propafenone, and thioridazine; increased toxicity with MAOI, sumatriptan, lithium, and TCAs; decreases metabolism/plasma clearance of some drugs (diazepam, tolbutamide), increasing their duration and effect; displaces highly bound protein drugs (eg, warfarin), resulting in increased effect

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in preexisting seizure disorders and in patients who have experienced a recent myocardial infarction, have unstable heart disease, and have hepatic or renal impairment; caution in agitated and/or hyperactive patients because the drug may induce active mania/hypomania; risk of suicide is inherent in depression


Doxepin (Sinequan)

Inhibits histamine and acetylcholine activity and has proven useful in treatment of various forms of depression associated with chronic and neuropathic pain. Prominent sedative effect. Useful in oral concentrate, 10 mg/mL, to titrate small doses.

Adult

2-100 mg PO qhs

Pediatric

<12 years: Not recommended
>12 years: 25-50 mg/d PO in single or divided doses

Decreases effect of bretylium, guanethidine, clonidine, and levodopa; effect decreased by ascorbic acid and cholestyramine; increases effect/toxicity of carbamazepine, amphetamines, thyroid preparations, and sympathomimetics; increased toxicity with coadministration of fluoxetine (seizures), thyroid preparations, MAOIs, albuterol, CNS depressants (eg, benzodiazepines, opiate analgesics, phenothiazines, alcohol), anticholinergics, and cimetidine

Documented hypersensitivity; urinary retention; acute recovery phase following myocardial infarction; glaucoma

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, and hyperthyroidism; pregnancy and lactation; avoid discontinuation of long-term high-dose therapy


Trazodone (Desyrel)

5-HT2–receptor antagonist that inhibits reuptake of 5-HT. Negligible affinity for cholinergic, adrenergic, dopaminergic, or histaminic receptors. Intermediate sedation activity.

Adult

50-150 mg PO qhs

Pediatric

Children: 1.5-2 mg/kg/d PO in divided doses, gradually increase q3-4d prn; not to exceed 6 mg/kg/d PO in 3 divided doses
Adolescents: 25-50 mg/d PO, increase to 100-150 mg/d PO in divided doses

Additive serotonergic effects with other serotonergic agents (eg, buspirone, MAOIs); additive hypotensive effective with other psychotropics (eg, low-potency antipsychotics); additive sedation and impaired motor skills with ethanol

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Infrequent anticholinergic or cardiac adverse effects; safety/efficacy in children <18 y not established; caution in cardiac disease and/or arrhythmias; very sedating; therapeutic effects may take as long as 4 wk


Fluoxetine (Prozac)

SSRI, less sedating than TCAs but appears to improve symptoms of pain.

Adult

10-40 mg PO qhs

Pediatric

Not established

Increased effect with TCAs; increased/decreased effect of lithium (increased and decreased levels reported); increased toxicity of diazepam and trazodone; displaces highly protein bound drugs (warfarin); coadministration with sumatriptan causes increased weakness, hyperreflexia, and incoordination

Documented hypersensitivity; current MAOI use or administration within past 14 d

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Anxiety, insomnia, and significant anorexia and weight loss; caution in hepatic impairment and seizures; add/initiate other antidepressant therapy with caution as long as 5 wk after discontinuing drug


Duloxetine (Cymbalta)

Potent neuronal serotonin inhibitor and norepinephrine reuptake inhibitor. Antidepressive action is theorized to be due to serotonergic and noradrenergic potentiation in CNS.

Adult

20 mg PO bid; may increase to 60 mg/d administered qd or divided as 30 mg PO bid

Pediatric

Not established

Metabolized by CYP1A2 and CYP2D6; coadministration with drugs that inhibit CYP1A2 (eg, fluvoxamine, cimetidine, ciprofloxacin, enoxacin) may increase duloxetine blood levels and toxicity; coadministration with drugs that inhibit CYP2D6 (eg, paroxetine, fluoxetine, quinidine) may increase duloxetine blood levels and toxicity; duloxetine moderately inhibits CYP2D6 and may decrease elimination of CYP2D6 substrates (eg, TCAs, phenothiazines [eg, thioridazine], type 1C antiarrhythmics [eg, propafenone, flecainide]); coadministration with MAOIs may cause serious, sometimes fatal, reactions that include hyperthermia, rigidity, myoclonus, autonomic instability, and mental status changes including extreme agitation, delirium, and coma (see contraindications)

Documented hypersensitivity; uncontrolled narrow-angle glaucoma; do not administer within 14 d after cessation of MAOIs or initiation of MAOIs within 5 d after cessation of duloxetine

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Observe closely for clinical worsening and suicidality when initiating treatment or following dosage change; gradually decrease dose when discontinuing (do not abruptly discontinue); caution in hepatic impairment or end-stage renal disease; recommended not to prescribe to patients with substantial alcohol use or evidence of chronic liver disease; may cause slight blood pressure increase; may activate mania or hypomania; common adverse effects include nausea, dry mouth, constipation, decreased appetite, fatigue, somnolence, and increased sweating

Nonsteroidal anti-inflammatory agents (NSAIDS)

Although most NSAIDs are used primarily for their anti-inflammatory effects, they are effective analgesics and are useful for the relief of mild-to-moderate pain.


Ibuprofen (Ibuprin, Advil, Motrin)

DOC for mild-to-moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Adult

200-800 mg PO tid

Pediatric

<6 months: Not established
>6 months: 30-70 mg/kg/d PO in divided doses q6-8h; not to exceed 400 mg/d if <20 kg, 600 mg/d if 20-30 kg, 800 mg/d if 30-40 kg, adult dose if >40 kg

May decrease effects of loop diuretics with coadministration; coadministration with anticoagulants may increase PT (monitor and watch for signs of bleeding); may increase serum lithium levels and risk of methotrexate toxicity; probenecid may increase toxicity of NSAIDs

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Nausea, heartburn, and GI bleeding; caution in CHF, hypertension, renal/hepatic impairment, and anticoagulant therapy; elderly people have increased risk for developing adverse effects (as many as 60% can develop peptic ulceration); compromises existing renal function, especially when CrCl <30 mL/min; CNS adverse effects (eg, confusion, agitation, hallucination) are generally observed in overdose or high-dose situations (elderly people can experience these effects at lower doses)

Centrally acting analgesics

Pain control is essential to quality patient care. Analgesics ensure patient comfort and have sedating properties.


Tramadol (Ultram)

Binds to mu opioid receptors and slightly inhibits reuptake of norepinephrine and serotonin.

Adult

50-100 mg PO q4-6h, titrate in 50-mg increments q3d to effective dose; not to exceed 400 mg qd

Pediatric

Not established

Decreases carbamazepine effects significantly; cimetidine increases toxicity; risk of serotonin syndrome with coadministration of antidepressants

Documented hypersensitivity; opioid dependency; concurrent use of MAOI or administration within 14 d; use of SSRIs, TCAs, and opioids; acute alcohol intoxication

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Less respiratory depression than opioids; can cause dizziness, nausea, constipation, sweating, and pruritus; additive sedation with alcohol and TCAs; abrupt discontinuation can precipitate opioid withdrawal symptoms; adjust dose in liver disease, myxedema, hypothyroidism, and hypoadrenalism; pregnancy and breastfeeding; seizure; development of tolerance or dependency occurs with extended use

Muscle relaxants

These agents are thought to work centrally by suppressing conduction in the vestibular cerebellar pathways. They may have an inhibitory effect on the parasympathetic nervous system.


Cyclobenzaprine (Flexeril)

Structurally similar to TCAs. Has anticholinergic and sedative adverse effects.

Adult

2.5-40 mg PO; 10 mg tid usually effective

Pediatric

Not established

Coadministration with MAOIs and TCAs may increase toxicity; cyclobenzaprine may have additive effect when used concurrently with anticholinergics; effects of alcohol, CNS depressants, and barbiturates may be enhanced with cyclobenzaprine

Documented hypersensitivity; current MAOI use or administration within 14 d; hyperthyroidism; CHF; arrhythmias

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Usual precautions of TCA therapy should be observed; caution in urinary hesitancy and angle-closure glaucoma

Anticonvulsants

These agents may alleviate chronic pain.


Gabapentin (Neurontin)

Membrane stabilizer, a structural analogue of inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which paradoxically is thought not to exert effect on GABA receptors. Appears to exert action via the alpha(2)delta1 and alpha(2)delta2 auxiliary subunits of voltage-gaited calcium channels. Used to manage pain and provide sedation in neuropathic pain.

Adult

100-1200 mg PO tid

Pediatric

<12 years: Not recommended
>12 years: Administer as in adults

Antacids may significantly reduce bioavailability of gabapentin (administer at least 2 h following antacids); may significantly increase norethindrone levels; cimetidine, hydrocodone, and morphine may increase gabapentin AUC; naproxen may increase gabapentin absorption

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Common adverse effects include drowsiness, dizziness, somnolence, and unwanted eye movements; children may experience emotional ability hostility, thought disorder, and hyperkinesia; caution in elderly patients and patients with severe renal impairment; abrupt withdrawal may precipitate seizures


Pregabalin (Lyrica)

Structural derivative of GABA. Mechanism of action unknown. Binds with high affinity to alpha2-delta site (a calcium channel subunit). In vitro, reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. Indicated for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, or fibromyalgia. It is also indicated for adjunctive therapy in partial-onset seizures.

Adult

75 mg PO bid initially; increase to 150 mg PO bid within 1 wk based on efficacy and tolerability; may further increase dose to 225 mg bid if needed

Pediatric

Not established

May cause additive effects on cognitive and gross motor functioning when coadministered with drugs that cause dizziness or somnolence

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue gradually (over a minimum of 1 wk) to minimize increased seizure frequency in patients with seizure disorders; may cause insomnia, nausea, headache, or diarrhea upon abrupt withdrawal; common adverse effects include dizziness, somnolence, blurred vision, weight gain, and peripheral edema; may elevate creatinine kinase level, decrease platelet count, and increase PR interval; doses >300 mg/d associated with higher rate of adverse effects and treatment discontinuation; decrease dose with renal impairment (ie, CrCl <60 mL/min); angioedema has been reported during postmarketing surveillance

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References
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Further Reading

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Keywords

nonarticular rheumatism, regional pain syndrome, soft tissue rheumatic pain syndrome, myofascial pain syndrome, repetitive strain injury, cumulative movement disorders, tendonitis, bursitis, neurovascular entrapment, multiple tendonitis and bursitis syndrome, fibromyalgia, fibrositis, FMS, temporomandibular joint syndrome, flatfoot, hypermobility syndrome, lateral epicondylitis, tennis elbow, carpal tunnel syndrome, thoracic outlet syndrome, regional myofascial pain syndrome, temporomandibular joint syndrome, multiple bursitis-tendonitis syndrome, enthesitis, golfer's elbow, entrapment syndrome, meralgia paresthetica, tarsal tunnel syndrome

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Contributor Information and Disclosures

Author

Daniel Muller, MD, PhD, Department of Internal Medicine, Section of Rheumatology, Associate Professor, University of Wisconsin at Madison
Daniel Muller, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American College of Rheumatology, and American Holistic Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Robert E Wolf, MD, PhD, Professor Emeritus, Department of Medicine, Louisiana State University Health Sciences Center at Shreveport; Chief, Rheumatology Section, Medical Service, Overton Brooks Veterans Administration Medical Center of Shreveport
Robert E Wolf, MD, PhD is a member of the following medical societies: American College of Rheumatology, Arthritis Foundation, and Society for Leukocyte Biology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Elliot Goldberg, MD, Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine
Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD, Professor of Medicine, Temple University School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital
Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa
Disclosure: medifocus Honoraria Review panel membership; health dialogs Honoraria Consulting; West Penn Allegheny Health System None Board membership

 
 
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