Dr Shepherd comments: Scientists uncover why long Covid can cause pain

April 6, 2022

Medical Xpress discusses a new animal study that they report has provided important insights into how COVID-19 SARS-CoV-2—the virus responsible for COVID-19—can lead to long-term pain. 


“A significant number of people suffering from long Covid experience sensory abnormalities, including various forms of pain,” said Randal (Alex) Serafini, an MD/Ph.D. candidate from the Icahn School of Medicine at Mount Sinai in New York City. “We used RNA sequencing to get a snapshot of the biochemical changes SARS-CoV-2 triggers in a pain-transmitting structure called dorsal root ganglia.”

Using a hamster model of SARS-CoV-2 infection, the researchers found that infection left a gene expression signature in the dorsal root ganglia that remained even after the virus cleared. The signature matched gene expression patterns seen in pain caused by other conditions.”

MEA Comments

Dr Shepherd, Honorary Medical Adviser to the ME Association says:

“The headline is very misleading – we have not yet discovered what causes pain in Long Covid: However, this is an interesting observation from a small research study in relation to what may be causing pain in Long Covid and the involvement of dorsal root ganglia – a part of the peripheral nervous system that lies outside the spinal cord and acts as a transmission centre for messages about pain and sensation going to the brain.

It is also interesting because, as some people may be aware, we have an ME/CFS post-mortem research group. And one of the findings from some of the post-mortems that have been carried out at Addenbrooke’s Hospital in Cambridge is dorsal root ganglionitis – meaning inflammation in the ganglia

So it is possible that viral-induced inflammation in this part of the nervous system could be involved in both pain and sensation disturbances in both ME/CFS and Long Covid.”

Below is a summary of the findings from some of these ME/CFS post-mortems that were published in the Journal of the Neurological Sciences

Post Mortem Findings**Trigger Warning: Suicide References**

Chronic Fatigue Syndrome: Pilot Study of Four Autopsy Cases – DG O’Donovan 1, 2, T Harrower 3, S Cader2, LJ Findley 2, C Shepherd 4, A Chaudhuri 2

1. Addenbrooke’s Hospital Cambridge UK
2. Queen’s Hospital Romford Essex UK
3. Royal Devon & Exeter Hospitals UK
4. Honorary Medical Advisor to ME Association UK

Chronic Fatigue Syndrome / Myalgic Encephalomyelitis is a disorder characterised by chronic exercise-induced fatigue, cognitive dysfunction, sensory disturbances and often pain. The aetiology and pathogenesis are not understood. We report the post mortem pathology of four cases of CFS diagnosed by specialists.

The causes of death were all unnatural and included: suicidal overdose, renal failure due to lack of food and water, assisted suicide and probable poisoning.
Selected portions of tissue were made available by the various Coroners in the UK and with the assent of the persons in a qualifying relationship.

The cases were 1 male, and 3 female. Ages (years) M32, F32, F43 & F31. One case showed a vast excess of corpora amylacea in the spinal cord and brain of unknown significance but Polyglucosan Body Disease was not supported by clinicopathological review. No ganglionitis was identified.

One case showed a marked dorsal root ganglionitis and two other cases showed mild excess of lymphocytes with nodules of nageotte in the dorsal root ganglia.
This raises the hypothesis that dysfunction of the sensory and probably also the autonomic nervous system may lead to abnormal neural activity eg hyperalgesia & allodynia rather than anaesthesia and may explain some of the symptoms of CFS / ME such as pain, hypotension, hyperacusis and photophobia. However, the syndrome may be heterogeneous.

Nevertheless, the precise relationship of fatigue, which may be either peripheral or central, to abnormalities in the peripheral nervous system (PNS) needs to be studied.
The differential diagnosis of ganglionitis should be investigated in CFS / ME patients hence Varicella Zoster, Lyme disease, HIV, Sjogren’s disease, paraneoplastic sensory ganglionopathy should be excluded by appropriate history and tests.

A thorough histopathological study of cases coming to autopsy may help to confirm or refute the hypothesis, that CFS is a disease process, and whether the symptomatology may be explained by inflammation of the sensory and autonomic divisions of the PNS. A specific CFS / ME brain and tissue bank in the UK is proposed.

Dr Charles Shepherd,
Trustee and
Hon. Medical Adviser
to the ME Association.
Member of the 2018-2021 NICE Guideline Committee.
Member of the 2002 Independent Working Group on ME/CFS.

Dr Charles Shepherd

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