The Chronic Pain Connection
From “hand-warmers” to ion channel blockers to magnetic field generators more and more different approaches to get at the basis of chronic pain are being tried. Now comes an entirely different approach.
First, studies indicated that in rodents, chronic pain neurons thought to be associated with negative emotions showed increased activity after the onset of the pain. Those neuron’s connections to other parts of the brain associated with depression, also increased. The neuronal activity was associated with a drop in dopamine levels.
Combining a Parkinson’s drug called L-dopa with a non-steroidal anti-inflammatory drug completely eliminated any signs that an animal model was feeling pain. A clinical trial in humans is underway.
L-dopa isn’t the first Parkinson’s disease drug found to reduce pain. Pramipexole, another dopamine enhancer, had a similar effect on rats with chronic pain. Pramipexole did pretty well in a 2005 controlled, double-blinded fibromyalgia study. FM patients reported a 35% decrease in pain and about 40% had a 50% or greater reduction in pain. Fatigue dropped by an average of 30%.
A Parkinson’s – ME/CFS/Fibromyalgia Connection?
Parkinson’s has never been explicitly connected to chronic fatigue syndrome or FM, but many of the secondary symptoms (muscle rigidity, increased muscle tone, contracted muscles, autonomic nervous system problems, gait problems, cognitive issues, sensory issues and mood disorders) can be found in both. Small fiber neuropathy – commonly found in FM – appears to be the cause of the sensory issues in Parkinson’s disease.
In Parkinson’s disease dopamine-producing neurons in the nucleus accumbens in the basal ganglia in the brain are destroyed. The neuron destruction sets off a variety of symptoms, the most prominent of which is the inability to move. First Parkinson’s disease patients experience shaking, rigidity, slowness of movement, difficulty walking and gait problems. Cognitive and behavioral problems arise later, and depression is common.
The Basal Ganglia Connection
Basal ganglia abnormalities have been implicated in all three diseases. Miller found that reduced activation of the basal ganglia was associated with reduced reward and fatigue in ME/CFS. Reduced blood flows to the basal ganglia were also recently associated with increased pain disability and the overall impact of fibromyalgia in FM patients.
- Unrewarding Reward: The Basal Ganglia, Inflammation and Fatigue In Chronic Fatigue Syndrome
- Dopamine, the Basal Ganglia and Chronic Fatigue Syndrome #II – Treatments
The basal ganglia is an intriguing organ which regulates not just movement and the autonomic nervous system, but cognition and emotions such as reward.
First, a look at the role basal ganglia problems may play in producing chronic pain and reward.
Chronic Pain, Emotions, Addiction and the Basal Ganglia
The neurons in the nucleus accumbens in the basal ganglia are activated by drugs such as opiates that produce euphoria or by participating in rewarding experiences such as sex, exercise, etc. The connection to the mesolimbic pathway – which is highly activated in addiction suggested to the researchers that the brain can become hardwired or addicted to producing pain. One asserted that the results indicate that chronic pain cannot be viewed as a purely sensory phenomenon but instead is closely related to emotions.
That’s no surprise. It’s clear that the anticipation of pain, for instance, results in increased pain. Anticipating pain could be viewed as the opposite of anticipating reward.
Miller’s ME/CFS study found that basal ganglia inactivity and reduced reward was associated with increased fatigue in ME/CFS. Reward is clearly a complex phenomenon that integrates emotions and motor activity. High reward states may be synonymous with increased motor activation and vice versa.
The Basal Ganglia and Movement
The basal ganglia are not just about emotions and reward, though. The primary function of the basal ganglia is to ensure that voluntary movements are carried out smoothly. It does this by regulating the activities of the motor and premotor cortical areas.
Excitatory neurotransmitters such as glutamate cause the basal ganglia to impair movement. Glutamate activates a pathway involving the basal ganglia which inhibits signals coming for the motor cortex. Dopamine-producing neurons in the basal ganglia, on the other hand, stimulate movement.
In Parkinson’s disease destruction of the dopamine-producing neurons puts the movement inhibiting portion of the brain on overdrive. Their muscles, for instance, remain in a state of contraction with a high muscle tone. This does not appear to be the result of muscle problems; their brains have simply lost the ability to tell them to move.
Autonomic Nervous System Breakdown
Recent findings suggest that autonomic nervous system problems run rampant in Parkinson’s. As in ME/CFS and FM, parasympathetic nervous system functioning is impaired. Problems with orthostatic intolerance are being found as well.
The autonomic nervous system findings in Parkinson’s strongly correlate with findings of small nerve fiber neuropathy. These findings are particularly intriguing since they suggest that, just as in fibromyalgia, Parkinson’s is more than a central nervous system disorder; the peripheral nervous system is also affected.
The Gait Studies
The first ME/CFS gait study in 1995 was prompted by Benjamin Natelson’s observations that people with ME/CFS walked differently. It proposed the gait problems it found were due to “balance problems, muscle weakness, or central nervous system dysfunction”.
Another gait study found that because the abnormalities seen began at the beginning of the ME/CFS patients walks they were not likely due to fatigue. Instead, they appeared to have a central nervous system explanation.
A 2008 study found that ME/CFS patients self-selected walking speed was much slower than average. In fact, ME/CFS patients were walking so slowly that their walking velocity was similar to that of above the knee amputees (!). The researchers attributed the reduced walking speed to the smaller slower steps the ME/CFS patients were taking.
A follow-up study using an oxygen uptake test found that ME/CFS patients used much more energy during walking than did the healthy controls. The ME/CFS patients, then, appeared to be attempting to reduce their energy expenditures by walking more slowly.
The researchers proposed several possible reasons for this including kinesophobia (a fear of movement leading to increased muscle activation and energy use), metabolic/mitochondrial issues and/or deconditioning. They noted that a similar issue is found in multiple sclerosis, stroke, and other disorders.
People with FM may experience similar limitations. One study found they used hip flexors more than usual -another more energetically intensive mode of walking – instead of their ankle flexors when they walked.
Slowed movement is one of the first symptoms seen in Parkinson’s disease. It is, again, associated with reduced dopamine in the brain. Miller’s studies suggest dopamine reductions may be present in ME/CFS as well.
Some similar symptoms, the basal ganglia problems, the dopamine reduction and the autonomic nervous system problems suggest ME/CFS and FM could have connections to Parkinson’s and other basal ganglia diseases.
The basal ganglia is a major organ containing several different sub-organs. Depending on the type of basal ganglia dysfunction found, several different diseases can result. They include Parkinson’s disease, Huntington’s disease, Tourette syndrome, dystonia, and addiction.
Perhaps at some point fatigue and pain disorders such as ME/CFS and FM will be added to the list.
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