Chronic pain and muscle tension in ADHD - neurophysiological correlates

For chronic pain and increased muscle tone as a symptom of ADHD, see Chronic pain / muscle tension in ADHD In the chapter Symptoms
For fibromyalgia as a comorbidity of ADHD see Fibromyalgia comorbid with ADHD in the article Diagnostics / Comorbidity in ADHD / Somatic comorbidities in ADHD

• 1. Chronic pain - development and causes
  • 1.1. Chronic pain and dopamine
  • 1.2. Other pathways for chronic pain in ADHD
  • 1.3. Pathways of development of fibromyalgia
• 2. Muscle tone - causes of development
  • 2.1. Muscle tone and dopamine
  • 2.2. Other pathways for high muscle tension in ADHD

1. Chronic pain - development and causes¶

1.1. Chronic pain and dopamine¶

The dopamine system could be involved in ADHD, chronic pain and the modulation of muscle tone¹² Chronic pain, depression and anxiety disorders show a high degree of comorbidity.³ Up to 80% of persons with ADHD or Parkinson’s disease report comorbid pain conditions, 2 to 3 times more often than non-affected people.³⁴ In Parkinson’s, musculoskeletal pain is the most commonly reported pain condition at 40%-90%.⁵⁴

The dopamine agonist apomorphine has an analgesic effect.⁶ Lesions of the dopaminergic terminals or the dopaminergic neurons in the midbrain (striatum, substantia nigra, VTA) cause pronounced pain reactions.⁷ Levodopa for Parkinson’s alleviates chronic pain.⁸
The dopaminergic mesolimbic reward circuit and the endocannabinoid system are involved in the pathology of chronic pain, both in pain perception and pain relief.³⁹¹⁰
In anesthetized rats, painful pinching of the tail triggers dopamine release in the dorsal striatum and NAc nucleus during the stimulus, and dopamine release in the NAc shell after termination.¹¹
Fibromyalgia, a chronic pain syndrome, is associated with a reduction in the release of dopamine¹²¹³ and reduced availability of D2/D3 receptors in the cortex¹⁴.
The mesolimbic reward circuit is involved in the perception of pain and the expectation of pain relief.¹⁵

Painful stimuli are encoded by the mesolimbic dopamine circuit. Chronic pain reduces tonic dopamine. A pain-induced reduction in tonic dopamine correlates with increased evoked phasic dopamine release.¹⁶ This is consistent with Grace’s model of decreased tonic and increased phasic dopamine firing in ADHD. See also Tonic and phasic dopamine in explanatory models of ADHD In the section Dopamine in the chapter Neurological aspects.
People with chronic pain show reduced responsiveness within the mesolimbic dopamine system to meaningful stimuli, reduced D2 receptor binding, reduced presynaptic dopamine activity in the striatum at rest and after an acute pain stimulus.¹⁷ In animals, chronic pain leads to decreased c-Fos activation in the VTA, decreased total dopamine levels and decreased D2 receptors in the striatum.¹⁷
Conversely, a reduction of dopamine in the brain by acute depletion of the dopamine precursors phenylalanine and tyrosine caused increased subjective pain sensitivity (the degree to which pain was perceived as unpleasant) without altering the sensory perception of pain.¹⁸
In 6-OHDA mice, in which dopamine synthesis is chemically damaged and which thus represent an ADHD animal model, an increased sensitivity to pain was found. The pain sensitivity was presumably mediated by α- and β-adrenergic and D2/D3 receptors. Atomoxetine¹⁹ such as MPH²⁰ was able to reduce the increased pain sensitivity in ADHD.
Stimulation of the substantia nigra, one of the two most important sources of dopamine in the brain, causes pain relief by activating spinal cord neurons via dopaminergic signaling pathways.²¹²²²³ Painful stimuli cause a release of dopamine in the dorsolateral striatum, which correlates with the subjective perception of pain intensity. The ventral striatum is also clearly associated with the emotional dimension of the human pain process and the expectation of pain.²⁴

In Parkinson’s disease, which is also characterized by dopamine deficiency, 30 to 50 % of people with ADHD suffer from increased sensitivity to pain.²⁵ This can be improved by dopaminergic medication²⁶, e.g. levodopa or deep brain stimulation.²⁷

Conversely, the perception of pain is reduced in schizophrenia, which is associated with increased dopamine levels.²⁸²⁹

The endocannabinoid system modulates the dopaminergic system in a variety of ways, including in relation to reward processing, and is also crucially involved in the perception of pain.³
More on the interaction between Endocannabinoids and dopamine In the article Cannabinoids in the section Neurotransmitters in the chapter Neurological aspects.

1.2. Other pathways for chronic pain in ADHD¶

Other common mechanisms for ADHD and chronic pain are discussed:¹

• Genetic factors³⁰
• Traumas³⁰³¹
• Pain receptors (opioid receptors, cannabinoid receptors, alpha-2-adrenoceptors)³⁰
• GABAergic neurosteroids (allopregnanolone, pregnanolone), progesterone³⁰
• Dysfunction of the HPA axis³⁰
• Neuroinflammation³⁰³²
• BDNF³⁰
• changed sensitivity to pain³²
• long-lasting muscle contraction, high muscle tone³³
  • almost 90% of children and adults with ADHD show motor dysregulation, which leads to persistently high muscle tone
  • this could contribute to the development of chronic muscle pain in ADHD³⁴
  • A highly significant correlation was found between muscular regulation problems and pain intensity³⁴
    • the ADHD group showed increased tone in the muscles of the neck, back, chest, shoulders, hips (i.e. the axial and proximal stabilizing muscles) and legs³⁴ Increased tone in these muscles was also found in children with ADHD.

1.3. Pathways of development of fibromyalgia¶

For fibromyalgia, an interplay of several pathogenic mechanisms has been proposed as a neurophysiological pathway:³⁵³¹

• Increase in the activity of the excitatory pain pathways bottom up
  • Increase in transmitters such as
    • Substance-P
    • Nitrogen oxide
    • Nerve growth factor (NGF)
    • Glutamate.
• Reduced activity of the inhibitory top-down pathways
  • reduced levels of
    • Dopamine
    • Noradrenaline
    • Serotonin
    • endogenous opioids
• Consequences of the imbalance of overactivated pain pathways and underactivated prefrontal inhibition:
  • functional central sensitization
  • which is developing into structural central sensitization
    • widespread reduction of the pain threshold
    • Increase in summation over time
    • prolonged after-effects of harmful stimuli
    • reduced general pain tolerance
• In addition, chronic sympathetic hyperactivity with increased sensitivity to acute stress exacerbates the symptoms of pain and fatigue
• HPA axis disturbed in the sense of chronic hypoactivity
  • Flattening of the daily cortisol fluctuations
    also promotes pain symptoms, fatigue and depression
• Peripheral pathogenic processes
  • Impairment of nociceptor sensitivity
  • immunological changes
  • local metabolic mechanisms in the muscles
    • ATP depletion
    • Lactic acid enrichment
    • Hypocarbia

Dopamine is also involved in fibromyalgia.²
Pain perception and attention influence each other.³⁶
In somatoform disorders such as fibromyalgia, irritable bowel syndrome, functional dyspeptic syndrome and temporomandibular joint dysfunction, melatonin is said to be a possible treatment option for pain symptoms.³⁷

2. Muscle tone - causes of development¶

2.1. Muscle tone and dopamine¶

Dopamine influences the tone of skeletal muscles and can therefore directly control movement:³⁸
The dopamine agonist apomorphine activated motoneurons of the trigeminal nerve and strongly increased the tone of the masseter (a chewing muscle) and tensor palatini (a muscle of the soft palate that supports swallowing). This excitatory effect is mediated by D1-like receptors, as specific activation of D1-like receptors increased muscle tone and blockade of these receptors prevented dopamine-induced activation of motor neurons. Blockade of D1-like receptors alone had no detectable effect on masseter/tensor palatini basal tone, suggesting that there is no functional dopamine drive on trigeminal motoneurons, at least during isoflurane anesthesia. In contrast, D2-like receptors did not affect the function of trigeminal motoneurons or the tone of masseter or tensor palatini.

In muscle tension tests, 64 to 84% of persons with ADHD showed severe impairment, compared to 0% of non-affected people.³⁹

Prolonged muscle tension can cause chronic pain.³³

An adult person with ADHD reported to us a massive decrease in his decades of massive neck/shoulder tension when he drastically reduced his chronic alcohol consumption.

2.2. Other pathways for high muscle tension in ADHD¶

• The reticular system
  • is involved in³⁴
    • Regulation of the arousals
    • Maintaining muscle tone.
  • The reticular formation can ³⁴
    • activate several muscles at the same time
    • Modulate body position adjustments for balance
    • this can affect the stabilizing muscles (the proximal limb muscles and muscles that stabilize the spine).
  • The reticulospinal system (the entirety of the descending fibers from the reticular formation) is important for³⁴
    • Regulation of posture control
    • Regulation of movements
    • Reduction in muscle activity during REM sleep