“It is not death or pain that is to be dreaded, but the fear of pain or death.”
– Epictetus

Fibromyalgia (FM)

See also:

Fibromyalgia – CAM Treatment

Central Sensitization

Mitochondrial Dysfunction

Gabapentin (Neurontin) & Pregabalin (Lyrica)



Hyperalgesia is an increased response to a stimulus which is normally painful.
Pain due to a stimulus which does not normally provoke pain.
Hyperalgesia has been frequently reserved for ‘nociceptor-mediated’ stimulus-evoked pain, whereas allodynia was regarded to be stimulus-evoked pain, mediated by receptors other than nociceptors. The usefulness of the concept allodynia in contrast to hyperalgesia has been debated since its existence.

Definitions and Terms Related to Pain

Key to Links:

Grey text – handout
Red text – another page on this website

Blue text – Journal publication


Fibromyalgia Syndrome (FM) – Symptoms and Manifestations

Fibromyalgia Syndrome (FM) is a chronic condition associated with widespread pain and is also often characterized by fatigue, non-restful sleep, anxiety, depression, cognitive impairment or “brain fog,” and disturbances in the nervous system, gastrointestinal system and urogenital system. The symptoms of FM frequently lead to functional impairment of daily living activities. There is an overall 6% to 15% prevalence rate in the United States, affecting an estimated 4 to 8 million adults, 90% of whom are women.  The cause of fibromyalgia remains unknown, but recent advances and discoveries have helped understand some of the mysteries of this disease.


Widespread Chronic Pain

The widespread pain of FM primarily involves the joints and muscles and is often described as a deep aching or burning pain along with stiffness, and tenderness of the muscles, tendons, and joints. The pain of FM is frequently characterized by hyperalgesia and allodynia (as defined above) that are believed to be a consequence of central sensitization (as described below). Treating the pain of FM is challenging because the mechanisms and causes of FM remain poorly understood and the conventional medications available provide limited benefit. (See below for specifics on the treatment of FM pain).


Central Sensitization (CS)

Fibromyalgia is a complex syndrome consisting of many characteristic elements that manifest differently in each individual afflicted with the condition. To understand fibromyalgia it is important to first understand the concept of “Central Sensitization (CS),a process that is yet to be fully understood but is the hallmark of fibromyalgia. Central Sensitization is characterized by altered pain thresholds such as hyperalgesia, a hypersensitive response to a painful stimulus and allodynia, a painful response to what should be a non-painful stimulus. (See Central Sensitization).



Dysautonomia is another manifestation of CS, a condition of the autonomic (or automatic) nervous system in which conditions not generally considered under conscious control such as heart rate, blood pressure, bowel activity or bladder activity become dysfunctional, giving rise to symptoms including palpitations, atypical chest pain, fluctuating blood pressures up and down, intestinal cramping or diarrhea, inappropriate sweating or flushing of the skin and other symptoms.


Fatigue and Non-Restful Sleep

Additional characteristic findings of FM are fatigue and non-restful sleep, affecting individuals with FM with different intensity but in many cases debilitating and life-changing. Current theory holds that the fatigue experienced with FMS is associated with mitochnodrial dysfunction. Mitochondria are functional components within each cell that process food for energy. They also manufacture antioxidants, essential agents for protecting cells from damage.  For more information regarding mitochondrial dysfunction including treatment options, see Mitochondrial Dysfunction.


Depression and Anxiety

While depression and anxiety are not specific to the diagnosis of FM, they both are common findings in those who suffer from fibromyalgia, demonstrating that FMS is considered the archetypical example of a chronic biopsychosocial pain disorder. Successful treatment of FM must address these associated psychiatric conditions.


Neck Injury and Positional Cervical Cord Compression (PC3)

There is ongoing controversy regarding the association of neck injury including cervical whiplash and spinal cord compression and their role in causation of fibromyalgia. Research is conflicting but studies do show an increase in widespread pain following spinal fractures, other traumatic injuries, and cervical spinal cord compression.

A recently emerging concept in the development of FM is that there may be an association between the presence of compression of the spinal cord in the neck and FM symptoms including dysautonomia. PC3 is defined as “cord abutment, compression or flattening with a spinal canal diameter of <10 mm by noted on special magnetic resonance (MRI) views (sagittal flexion, neutral, and extension images).” In an article published in 2008, a disproportionately high prevalence of PC3 was noted in FM patients and surgical treatment of the cord compression resulted in the resolution of FM symptoms in some patients.

Fibromyalgia Treatment

The successful treatment of fibromyalgia (FMS) requires an approach that integrates not just pain management but also the management of fragmented, non-restful sleep, fatigue, associated anxiety and depression and the cognitive impairment, or “brain fog” characteristic of fibromyalgia in which short term memory and cognitive processing are disrupted.

Conventional Management of FMS

Conventional management of FMS has focused on the use of prescription medications including the neuromodulating agents (anti-convulsants and antidepressants) and opioids along with behavioral approaches including exercise and cognitive behavior therapy (CBT). The pain of FMS is generally poorly controlled with most opioid analgesics while the anti-convulsants and antidepressants have limited benefit and tolerability. Exercise is beneficial for some, intolerable for others but rarely profoundly effective for the pain. CBT is helpful in improving coping skills and, over time, is associated with some, but often inadequate, reduction of pain.


Complementary and Alternative Medicine (CAM) Approaches to FMS

Complementary and Alternative Medicine (CAM) approaches to managing FMS offer substantial, effective means of combatting many of the FMS symptoms most disruptive to quality of life (QOL). Many CAM supplements offer definitive benefits. Mindful exercises including meditation, yoga and tai chi offer significant value in the control of FMS symptoms. Recent research demonstrates that music therapy is promising option in improving FMS. While the following paragraphs outline some of the best conventional treatment alternatives available, complementary and alternative medicine (CAM) approaches offer significant value in the control of FMS symptoms.

Please also see: Fibromyalgia – CAM Treatment


 Conventional Medications used in Treating FMS


While many conventional opioids offer limited benefit for fibromyalgia pain, some opioids do provide more favorable results. Insights into how or why these particular opioids can be more effective can be obtained by reading about the “neurobiology of pain” and reading about the specific medications linked below. Opioids are generally best avoided in the management of FM but it is common for the FM patient to have comorbid chronic pain conditions that do benefit from the use of opioids. The best choices of opioids for chronic pain with comorbid fibromyalgia pain typically include those opioids also believed to have SNRI properties and NMDA antagonist properties.

See: Opioids, Neurobiology of OpioidsNeurobiology of Pain):


  1. tramadol (Ultram, Ultracet)
  2. tapentadol (Nucynta)
  3. methadone (Dolobid)
  4. levorphanol
  5. buprenorphine (Butrans, Belbuca, Suboxone, Zubsolv, Bunavail)


Anti-Epileptic Drugs (AEDs)

Some of the most effective medications for treating fibromyalgia pain belong to the class of medications referred to as  anti-convulsants or “anti-epileptic drugs” (AEDs) because they were originally used to treat seizures based on their ability to reduce inappropriate nerve activity. The most effective AEDs for managing FM are:


  1. gabapentin (Neurontin, Gralise, Horizant)
  2. pregabalin (Lyrica) – FDA approved for FM
  3. topiramate (Topamax)




The two classes of antidepressants most effective in treating FM pain are the SNRIs (serotonin and norepinephrine uptake inhibitors) and the tricyclic antidepressants. The SSRI class of antidepressants have shown little benefit for the pain of FM in most studies although they may benefit the anxiety and or depression that may accompany FM.


SNRI antidepressants:

  1. Duloxetine (Cymbalta) – FDA approved for FM
  2. Venlafaxine (Effexor)
  3. Milnacaprine (Savella) – FDA approved for FM


Tricyclic antidepressants:

  1. Amitriptyline (Elavil)
  2. Doxepin
  3. Imipramine
  4. Desipramine
  5. Nortriptyline


NMDA Antagonists

While the NMDA antagonists (see Neurobiology of Fibromyalgia) have shown to be beneficial for both neuropathic pain and the pain associated with fibromyalgia, they can sometimes be associated with limiting side effects. Ketamine is gaining more evidence of benefit for some neuropathic pain conditions, its benefit for fibromyalgia is probably best advantageous when used topically (see below).

For additional information, see ketamine and dextromethorphan

For information on opioids with NMDA antagonist activity, see methadone and levorphanol.


A pioneer 2014 study evaluated memantine (Namenda) in fibromyalgia for a period of 6 months showing significant benefits in not just the pain of fibromyalgia but it demonstrated significant improvement in reported quality of life, mood enhancement and cognitive functioning (improvement of the ‘brain fog” often accompanyig fibromyalgia).


Memantine is extraordinarily well tolerated even in the elderly where it has sustained an excellent safety record in managing a variety of neurodegenerative disorders. Side effects are generally limited to infrequent mild headaches, drowsiness and dizziness which generally resolve on their own, although hallucinations have been reported. Doses range from 10mg to 30mg/day.



A recent study published in 2015 suggests testosterone transdermal gel applied once a day by fibromyalgia patients can be effective for chronic pain. A link between testosterone and pain is believed and testosterone is viewed as a possible important additional therapeutic that has the potential to be safe and effective for FMS pain.



Topical Medications

Topical medications are generally not very helpful in FM, but ketamine and lidocaine can sometimes be effective. Ketamine can be compounded by a compounding pharmacy as formulated by your physician. Lidocaine is available topically over the counter and can also be included in more potent concentrations along with ketamine by a compounding pharmacist.

  1. Ketamine
  2. Lidocaine

For additional information on fibromyalgia, see below and see Central Sensitization.


Fibroguide  – An excellent resource for self-directed treatment for FM

Reference Articles:

Fibromyalgia – Overviews

  1. FM research – National Fibromyalgia Association – 2008
  2. Fibromyalgia Syndrome – An Overview of Pathophysiology, Diagnosis and Management – 2012
  3. Fibromyalgia – a critical digest of the recent literature 2013
  4. Neurobiology-of-fibromyalgia-and-chronic-widespread-pain-2016

Fibromyalgia – Biomarkers

  1. Inflammatory:stress feedback dysregulation in women with fibromyalgia. 2012 – PubMed – NCBI
  2. unique-cytokine-signature-in-the-plasma-of-patients-with-fibromyalgia-2014
  3. Is fibromyalgia-related oxidative stress implicated in the decline of physical and mental health status? – PubMed – NCBI
  4. Clinical Symptoms in Fibromyalgia Are Better Associated to Lipid Peroxidation Levels in Blood Mononuclear Cells Rather than in Plasma – 2011

Fibromyalgia – Central Sensitization

  1. Fibromyalgia – The Unifying Concept of Central Sensitivity Syndromes
  2. Fibromyalgia patients show an abnormal dopamine response to pain. – PubMed – NCBI
  3. Neurophysiologic evidence for a central sensitization in patients with fibromyalgia – 2003
  4. Fibromyalgia Syndrome- A Central Role for the Hippocampus—A Theoretical Construct
  5. What Fibromyalgia Teaches Us About Chronic Pain – 2013
  6. Evidence of central inflammation in fibromyalgia — Increased cerebrospinal fluid interleukin-8 levels 2012

 Fibromyalgia –  Cognitive Impairment

  1. Cognitive Function & Fibromyalgia

Fibromyalgia – Disability

  1. Adjudication of fibromyalgia syndrome – Challenges in the medicolegal arena – 2014
  2. Fibromyalgia and disability adjudication – Letter – 2014
  3. Fibromyalgia and disability adjudication – Letter to the Editor 2014
  4. Fibromyalgia and disability adjudication – No simple solutions to a complex problem – 2014

Fibromyalgia – Dysautonomia

  1. A Novel Holistic Explanation for the Fibromyalgia Enigma – Autonomic Nervous System Dysfunction
  2. Sympathetic Nervous System Dysfunction in Fibromyalgia, Chronic Fatigue Syndrome, Irritable Bowel Syndrome, and Interstitial Cystitis
  3. Dysauatonomic Features Often Found in PC3

Fibromyalgia – Fatigue

  1. Beyond pain in fibromyalgia – insights into the symptom of fatigue
  2. Fatigue_FM

Fibromyalgia – Genetics

Fibromyalgia – Genetics: COMT

  1. Stress, the stress response system, and fibromyalgia


Fibromyalgia – Oxidative Stress

(See also: Antioxidants and NRF2 Activators)

  1. Oxidative Stress in Fibromyalgia – Pathophysiology and Clinical Implications – 2011
  2. Oxidative Stress in Fibromyalgia and its Relationship to Symptoms – 2009
  3. Is fibromyalgia-related oxidative stress implicated in the decline of physical and mental health status? – PubMed – NCBI
  4. Clinical Symptoms in Fibromyalgia Are Better Associated to Lipid Peroxidation Levels in Blood Mononuclear Cells Rather than in Plasma – 2011


Fibromyalgia – Mitochondrial Dysfunction

(See also: Antioxidants and NRF2 Activators)

  1. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients – 2013
  2. Oxidative stress and mitochondrial dysfunction in fibromyalgia. – PubMed – 2010
  3. Roles of Reactive Oxygen and Nitrogen Species in Pain – 2011
  4. Is Inflammation a Mitochondrial Dysfunction-Dependent Event in Fibromyalgia? – 2012
  5. Metformin and caloric restriction induce an AMPK-dependent restoration of mitochondrial dysfunction in fibroblasts from Fibromyalgia patients. 2015 – PubMed – NCBI


Fibromyalgia – Obesity

  1. Fibromyalgia and obesity: the hidden link. – PubMed – NCBI


Fibromyalgia – Positional Cervical Cord Compression (PC3)

  1. Clinical evidence for cervical myelopathy due to Chiari malformation and spinal stenosis in a non-randomized group of patients with the diagnosis of fibromyalgia
  2. Positional Cervical Spinal Cord Compression and Fibromyalgia 2008
  3. Why You Should Be Thinking About Positional Cervical Cord Compression
  4. Using Dynamic MRI to Diagnose Neck Pain PC3 – 2012
  5. Dysautonomic Features Often Found in PC3
  6. Determination of Fibromyalgia Syndrome Following Whiplash Injuries – 2011
  7. Chronic widespread bodily pain is increased among individuals with history of fracture – 2016
  8. A prospective study of the 1-year incidence of fibromyalgia after acute whiplash injury – 2015


Fibromyalgia – Treatment (Tx)

For information about effective CAM treatment for Fibromyalgia: CAM – Fibromyalgia


Fibromyalgia Tx – Overviews

  1. Current concepts in the treatment of fibromyalgia – 2013
  2. Innovative Approaches for the Complexity of Fibromyalgia – 2013
  3. What Fibromyalgia Teaches Us About Chronic Pain – 2013
  4. Systematic review and network meta-analysis of interventions for fibromyalgia – a protocol – 2013
  5. Is it necessary to strictly diagnose fibromyalgia syndrome in patients with chronic widespread pain? – 2014
  6. Fibromyalgia or chronic widespread pain – Does it matter? – 2015
  7. Comparative efficacy of pharmacological and non-pharmacological interventions in fibromyalgia syndrome – network meta-analysis – 2012
  8. Fibromyalgia Syndrome in Need of Effective Treatments – 2015
  9. Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma – 2017
  10. Treatment of fibromyalgia – 2017
  11. Alternatives to Opioids in the Pharmacologic Management of Chronic Pain Syndromes: A Narrative Review of Randomized, Controlled, and Blinded Clinic… – PubMed – NCBI
  12. Review of pharmacological therapies in fibromyalgia syndrome – 2014
  13. Update on Treatment Guideline in Fibromyalgia Syndrome with Focus on Pharmacology – 2017
  14. Association between initial opioid use and response to a brief interdisciplinary treatment program in fibromyalgia – 2019

Fibromyalgia Tx – CBT  

See:  Fibromyalgia – Complementary and Alternative Medicine CAM) Treatment

  1. CBT and Pain Management


Fibromyalgia Tx –  Diet 

See:  Diet & Fibromyalgia



Fibromyalgia Tx – Medications


Fibromyalgia Tx Medications – Anti-epileptics and Antidepressants

Fibromyalgia Tx – Gabapentin (Neurontin)

  1. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. – PubMed – NCBI


Fibromyalgia Tx – Pregabalin (Lyrica)

  1. Comparative Efficacy And Harms Of Duloxetine, Milnacipran, And Pregabalin In Fibromyalgia Syndrome 2010
  2. Coenzyme Q10 supplementation alleviates pain in pregabalin-treated fibromyalgia patients via reducing brain activity and mitochondrial dysfunction – PubMed – 2019



Fibromyalgia Tx – Duloxetine (Cymbalta)

  1. Duloxetine for treating painful neuropathy, chronic pain or fibromy… – PubMed – NCBI
  2. Comparative Efficacy And Harms Of Duloxetine, Milnacipran, And Pregabalin In Fibromyalgia Syndrome 2010


Fibromyalgia Tx – Milnacaprin (Savella)

  1. Efficacy and safety of milnacipran 100 mg:day in patients with fibromyalgia
  2. Comparative Efficacy And Harms Of Duloxetine, Milnacipran, And Pregabalin In Fibromyalgia Syndrome 2010
  3. Milnacipran for the treatment of fibromyalgia in adults: a 15-week,… – PubMed – NCBI
  4. Role and rationale for the use of milnacipran in the management of fibromyalgia
  5. Savella Brings Relief Long-Term in Fibromyalgia – in Meeting Coverage, ACR from MedPage Today
  6. Results of switching to milnacipran in fibromyalgia patients with an inadequate response to duloxetineMilnacipran combined with pregabalin in fibromyalgia


Fibromyalgia Tx – Mirtazapine (Remeron)

  1. Efficacy and safety of mirtazapine in fibromyalgia syndrome patients: a randomized placebo-controlled pilot study. – PubMed – NCBI


Fibromyalgia Tx – Amitriptyline (Elavil)

  1. A Brief Review of the Pharmacology of Amitriptyline and Clinical Outcomes in Treating Fibromyalgia – 2017

Fibromyalgia Tx – Testosterone

  1. a-novel-use-for-testosterone-to-treat-central-sensitization-of-chronic-pain-in-fibromyalgia-patients-2015

Fibromyalgia Tx – Tramadol

  1. Efficacy of tramadol in treatment of pain in fibromyalgia. – PubMed – NCBI – 2000


CAM, FMS Tx – Clonidine

  1. Analgesic synergy between opioid and α2-adrenoceptors – 2014
  2. Clonidine May Help in Chronic Fatigue Syndrome (CFS) and Fibromyalgia Because – 2013
  3. Idiopathic Peripheral Neuropathy Responsive to Sympathetic Nerve Blockade and Oral Clonidine – 2012
  4. Clonidine – clinical pharmacology and therapeutic use in pain management
  5. Clonidine for management of chronic pain – A brief review of the current evidences – 2014
  7. Topical clonidine for neuropathic pain – 2015



Fibromyalgia Tx – Dopamine Agonists/Support

Fibromyalgia Tx, Dopamine Agonist Pramipexole (Mirapex)

  1. Pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications

Fibromyalgia Tx, Dopamine Agonist Synaptamine

  1.  A Multi-Locus Approach to Treating Fibromyalgia by Boosting Dopaminergic Activity in the Meso-Limbic System of the Brain
  2. Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic treatment targets for chronic pain conditions – 2009


Fibromyalgia Tx – Gaba Agonists

Fibromyalgia Tx, Gaba Agonist Sodium Oxybate

  1. Sodium Oxybate – A Potential New Pharmacological Option for the Treatment of Fibromyalgia Syndrome – 2011
  2. Sodium oxybate therapy provides multidimensional improvement in fibromyalgia 2012

Fibromyalgia Tx – Opioids

  1. Endogenous opioidergic dysregulation of pain in fibromyalgia – a PET and fMRI study – 2017
  2. Geographic Variation of Chronic Opioid Use in Fibromyalgia – 2013

Fibromyalgia Tx, Opioids – Levorphanol

  1. Fibromyalgia Syndrome- A Central Role for the Hippocampus—A Theoretical Construct


Fibromyalgia Tx – NMDA Antagonists

Fibromyalgia Tx – NMDA Antagonists Overviews

  1. Modulation of NMDA Receptor Activity in Fibromyalgia – 2017


Fibromyalgia Tx – Memantine

  1. memantine-medlineplus-drug-information
  2. the-emerging-role-of-nmda-antagonists-in-pain-management
  3. changes-in-metabolites-after-treatment-with-memantine-in-fibromyalgia-a-double-blind-randomized-controlled-trial-with-magnetic-resonance-spectrosc-pubmed-ncbi
  4. combined-use-of-pregabalin-and-memantine-in-fibromyalgia-syndrome-treatment-a-novel-analgesic-and-neuroprotective-strategy-2009
  5. efficacy-of-memantine-in-the-treatment-of-fibromyalgia-a-double-blind-randomised-controlled-trial-with-6-month-follow-up-pubmed-ncbi
  6. evaluation-of-the-efficacy-of-memantine-in-the-treatment-of-fibromyalgia-study-protocol-for-a-doubled-blind-randomized-controlled-trial-with-six-month-follow-up_-2013
  7. Modulation of NMDA Receptor Activity in Fibromyalgia – 2017


Fibromyalgia TxOther

Fibromyalgia Tx – Metformin

  1. Metformin and caloric restriction induce an AMPK-dependent restoration of mitochondrial dysfunction in fibroblasts from Fibromyalgia patients. 2015 – PubMed – NCBI

Fibromyalgia Tx – Naltrexone

  1. Effects of Naltrexone on Pain Sensitivity and Mood in Fibromyalgia – 2009
  2. Low-Dose Naltrexone Eases Pain and Fatigue of Fibromyalgia
  3. Low-Dose Naltrexone Effective Therapy for Fibromyalgia
  4. Naltrexone for Fibromyalgia – Learn About Research Studies!


Fibromyalgia Tx – Antipsychotics

  1. Antipsychotics for fibromyalgia in adults. – PubMed – NCBI


Fibromyalgia Tx – Exercise

  1. Aerobic exercise in fibromyalgia: a practical review. – PubMed – NCBI
  2. Aquatic exercise training for fibromyalgia. – PubMed – NCBI
  3. Autonomic nervous system profile in fibromyalgia patients and its m… – PubMed – NCBI
  4. Resistance exercise training for fibromyalgia. – PubMed – NCBI


Fibromyalgia Tx – Fibromyalgia

  1. Benefits of a self-myofascial release program on health-related quality of life in people with fibromyalgia: a randomized controlled trial. – PubMed – NCBI – 2017
  2. Effects of myofascial release techniques on pain, physical function, and postural stability in patients with fibromyalgia: a randomized controlled … – PubMed – NCBI – 2011
  3. Effectiveness of different styles of massage therapy in fibromyalgia – A systematic review and meta-analysis – 2015

Fibromyalgia Tx – Spa therapy

  1. Fibromyalgia Syndrome and Spa Therapy – Myth or Reality?

Emphasis on Education


Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.


For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.


Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.


For more information, please contact Accurate Clinic.


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