Neuropathic Pain Affects Up To 34.3 Percent Of Individuals With Long COVID


A study by researcher from University of Sheffield-UK, University of Cyprus-Cyprus and Kapodistrian University of Athens-Greece has found that the prevalence of neuropathic pain among Long COVID individuals is about 34.3 percent.

Neuropathic pain can be defined as a process occurring after a primary lesion or disease of the somatosensory nervous system.1 This condition is the result of a series of different pathological mechanisms and it is usually described based on the anatomic localization or etiology.

The conditions and the pathophysiological states that determine the onset of neuropathic pain mostly involved are metabolic disorders (e.g. peripheral diabetic neuropathy (PDN)), neuropathies associated with viral infections (e.g. post-herpetic neuralgia, HIV, leprosy), autoimmune disorders affecting the central nervous system (e.g. multiple sclerosis and Guillain–Barre syndrome), chemotherapy-induced peripheral neuropathies, damage to the nervous system of traumatic origin (e.g. spinal cord injury (SCI) and amputation), inflammatory disorders, hereditary neuropathies, and channelopathies.2

Among the signs and the symptoms connected to the presence of neuropathic pain are allodynia (pain due to a stimulus that does not normally provoke pain), hyperalgesia (an increase in the perception of pain generated by a stimulus that causes pain), and paresthesia (a condition that determines the perception of anomalous sensations comparable to needle bites, tingling, itching, reduced, or even loss of sensitivity).

In patients suffering from neuropathic pain, the perceived pain is usually spontaneous, manifesting itself without needing a stimulus. This pathological condition substantially affects the quality of life of patients, compromising their psychological state.3

In the global population, the incidence and prevalence of neuropathic pain are difficult to estimate due to the lack of consensus on the definition of neuropathic pain. In a systematic review of the epidemiology of chronic pain, a prevalence between 3% and 17% was found, while the incidence was calculated in 3.9–42.0/100,000 person-years for post-herpetic neuralgia; 12.6–28.9/100,000 person-years for trigeminal neuralgia; 15.3–72.3/100,000 person-years for PDN, and 0.2–0.4/100,000 person-years for glossopharyngeal neuralgia.

Moreover, neuropathic pain was more prevalent among women (60.5% of patients), reached a peak at 50–64 years of age, and was more frequently reported by manual workers, as well as among people from rural areas.4

In this article, after a brief summary of drugs recommended for neuropathic pain, we focused on completed phase III clinical trials and on the preclinical studies performed in the last 2 years.

We have evaluated the completed phase III clinical studies available on, excluding the recommended drugs and the combination therapies. We also investigated the spinal cord stimulation (SCS) as a non-pharmacological approach. The researches were conducted on PubMed using “spinal cord stimulation” and “pain” as keywords and including only data that were published from January 2018 to December 2018. Preclinical studies were selected on PubMed using the following keywords: “neuropathic pain” and “animal model” and “treatment.” The results of the available studies concerning new therapeutic strategies, published in the last 2 years, have been discussed.

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The study findings were published in the peer reviewed Journal of Clinical Medicine.

This review aimed to establish the prevalence of neuropathic pain following a COVID-19 infection. Although neuropathic pain can be a symptom in the acute phase of COVID-19 (the pooled prevalence for hospitalised patients was 6.7%), it is more common in the context of long COVID syndrome as it affects more than 1 in 3 sufferers (the pooled prevalence was 34.3%).

The current literature suggests that long COVID syndrome affects one in three of those infected with COVID-19 [34]. Therefore, one in nine of those infected with COVID-19 will develop neuropathic pain. This is a significant number of people, considering the millions who have been infected with COVID-19 (Mercer and Salit, 2021).

The COVID-19-related neuropathic pain predictors that proved to be significant in the literature included the COVID-19 severity (hospitalised cohorts) [24], prolonged ICU prone positioning [25], azithromycin use and depression [31]. Therefore, psychological interventions to treat depression might prove useful in reducing the risk of COVID-19-related neuropathic pain. This is quite significant, considering 61% of COVID-19 patients were seeking neuropathic pain treatments at the follow-up [23].

Our findings should be interpreted with caution, given a few limitations. First, a gender bias impacted certain samples [24,25], possibly preventing detectable differences from being uncovered. Future replications require equally balanced samples. Second, most studies lacked control groups. Third, our search was restricted to a single database (PubMed).

Despite the fact that PubMed is the largest medical database where the majority of (if not all) high-quality studies appear, there was a small risk that we might have missed a few relevant papers. Finally, publication bias may occur in systematic reviews and could have undermined the validity of the results. This was reflected in the significant heterogeneity among the studies of long COVID patients.

In conclusion, in this review we highlighted the prevalence and predictors of COVID-19-related neuropathic pain. More research is needed in the future to explore these findings in more detail, considering that several patients have been left unable to function due to neuropathic pain following COVID-19 [27].


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