The patient from the case above returns for follow-up three months later. Sleep has improved ‘somewhat’ since initiation of amitriptyline, but she continues to suffer from daytime fatigue, widespread muscle pain and malaise. No focal joint issues have arisen and outside of her chronic IBS she has no other symptom complaints. She has some continued anxiety revolving around her job, but denies depression.

Her exam is similar to the prior evaluation, with diffuse muscle tenderness in response to examiner palpation, no active synovitis, and no signs of localized organ abnormality.

During discussion with the patient she expresses frustration: “I don’t understand why my lab tests are normal. I have been told that amitriptyline is an anti-depressant. This isn’t just ‘all in my head’. Can you tell me what caused this to happen?”

What is the current evidence behind the pathophysiology of fibromyalgia, and how can you use this information to provide patient-level counseling?

• Fibromyalgia stems from abnormal pain processing pathways (central amplification of pain)
• Research has identified objective evidence of: decreased pain threshold on functional brain MRI as well as abnormal levels of neurotransmitters involved in pain signaling in the spinal cord and brain
• Patients with fibromyalgia have increased levels of neurotransmitters involved in ascending nociceptive pathways (substance P, glutamate), and decreased levels of neurotransmitters involved in inhibitory, descending pathways (serotonin, norepinephrine, dopamine)
• It is uncertain whether other features of fibromyalgia (mood disturbance, poor sleep, fatigue) are related to central amplification of pain
• The trigger or inciting event leading to central amplification is uncertain; the local environment at peripheral nociceptors may initially play a role, but subsequent amplification of central signaling appears to be independent of peripheral factors
• An understanding of central pain amplification is important because it is thought to have a prominent role in conditions such as IBS, interstitial cystitis, TMJ disorder, and perhaps in osteoarthritis as well

Counseling on the above is provided. It is explained that patients with fibromyalgia have dysfunctional pain processing pathways in which the ‘volume is inappropriately turned up’. The patient expresses thanks for explaining her condition, but wonders if there are other treatment options other than amitriptyline.

Describe pharmacologic and non-pharmacologic approaches to the treatment of fibromyalgia?

Non-pharmacologic therapies include: patient education, exercise and cognitive behavioral therapy. Pharmacologic therapies should be tailored to individual patient symptoms such as concurrent depression, insomnia, soft tissue pain, and/or comorbid conditions such as IBS.

Pharmacologic options may include: gabapentin and pregabalin (which may exert effect through reduction of neurotransmitters such as substance P and glutamate), tramadol (with opioid receptor activity, but also dual serotonin/norepinephrine reuptake inhibition-SNRI), tricyclic agents (SNRI activity), cyclobenzaprine (muscle relaxant and SNRI activity), venlafazine (SNRI activity) and newer agents such as duloxetine, milnacipran, and desvenlafaxine.