Tag: motor neuron changes

Hyperactivation of proprioceptors induces microglia-mediated long-lasting pain in a rat model of chronic fatigue syndrome

Abstract:

BACKGROUND: Patients diagnosed with chronic fatigue syndrome (CFS) or fibromyalgia experience chronic pain. Concomitantly, the rat model of CFS exhibits microglial activation in the lumbar spinal cord and pain behavior without peripheral tissue damage and/or inflammation. The present study addressed the mechanism underlying the association between pain and chronic stress using this rat model.

METHODS: Chronic or continuous stress-loading (CS) model rats, housed in a cage with a thin level of water (1.5 cm in depth), were used. The von Frey test and pressure pain test were employed to measure pain behavior. The neuronal and microglial activations were immunohistochemically demonstrated with antibodies against ATF3 and Iba1. Electromyography was used to evaluate muscle activity.

RESULTS: The expression of ATF3, a marker of neuronal hyperactivity or injury, was first observed in the lumbar dorsal root ganglion (DRG) neurons 2 days after CS initiation. More than 50% of ATF3-positive neurons simultaneously expressed the proprioceptor markers TrkC or VGluT1, whereas the co-expression rates for TrkA, TrkB, IB4, and CGRP were lower than 20%. Retrograde labeling using fluorogold showed that ATF3-positive proprioceptive DRG neurons mainly projected to the soleus. Substantial microglial accumulation was observed in the medial part of the dorsal horn on the fifth CS day. Microglial accumulation was observed around a subset of motor neurons in the dorsal part of the ventral horn on the sixth CS day. The motor neurons surrounded by microglia were ATF3-positive and mainly projected to the soleus. Electromyographic activity in the soleus was two to three times higher in the CS group than in the control group. These results suggest that chronic proprioceptor activation induces the sequential activation of neurons along the spinal reflex arc, and the neuronal activation further activates microglia along the arc. Proprioceptor suppression by ankle joint immobilization significantly suppressed the accumulation of microglia in the spinal cord, as well as the pain behavior.

CONCLUSION: Our results indicate that proprioceptor-induced microglial activation may be a key player in the initiation and maintenance of abnormal pain in patients with CFS.

Source: Yasui M, Menjyo Y, Tokizane K, Shiozawa A, Tsuda M, Inoue K, Kiyama H. Hyperactivation of proprioceptors induces microglia-mediated long-lasting pain in a rat model of chronic fatigue syndrome. J Neuroinflammation. 2019 Mar 30;16(1):67. doi: 10.1186/s12974-019-1456-x. https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-019-1456-x (Full article)

A comparative review of systemic and neurological symptomatology in 12 outbreaks collectively described as chronic fatigue syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis

Abstract:

Outbreaks of illnesses of unknown etiology typified by a chronic relapsing course of constitutional symptoms and nervous system involvement have collectively been referred to as chronic fatigue syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis. To examine heterogeneity of clinical presentation, a comparative review was undertaken for 12 well-documented outbreaks reported since 1934.

A systemic syndrome characterized by excessive fatigue, myalgias, headache, low-grade fever, and other constitutional symptoms was common to cases in all outbreaks. However, marked heterogeneity in the range of neurological features was apparent.

On the basis of predominant neurological manifestations, outbreaks could be grouped into four levels of increasing neurological involvement: affective neuropsychological changes (level I); prominent cutaneous sensory symptoms with both affective and cognitive neuropsychological changes (level II); marked objective paresis with cutaneous sensory as well as affective and cognitive neuropsychological changes (level III); and cutaneous sensory, affective and cognitive neuropsychological, posterior column, cranial nerve, and mixed upper and lower motor neuron changes (level IV). Groups with the most prominent objective neurological findings (levels III and IV) comprised exclusively outbreaks reported between the 1930s and 1950s. All but one outbreak in groups with less prominent neurological findings (levels I and II) were reported between the 1960s and 1980s; a range of neurological features was observed for these groups.

Because a complete neurological examination is not emphasized as part of the diagnostic workup in current outbreaks, it is possible that less obvious neurological findings may be overlooked. Careful evaluation of neurological features in epidemic and endemic cases of what is now called chronic fatigue syndrome may be one approach to distinguishing subtypes of what has been described in the past as a nosological entity.

 

Source: Briggs NC, Levine PH. A comparative review of systemic and neurological symptomatology in 12 outbreaks collectively described as chronic fatigue syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis. Clin Infect Dis. 1994 Jan;18 Suppl 1:S32-42. http://www.ncbi.nlm.nih.gov/pubmed/8148451