Does COVID-19 affect pain processing?

When the SARS-COV-2 pandemic hit in 2020, the impact on daily lives and health was felt around the world. Between lock-downs, change of daily routine, and isolation, some with chronic pain have coped with increase of their pain complaints and interference (Fallon, 2021) (Clauw, 2020) (Mun, 2021).

COVID-19 and pain

For those infected, coronavirus disease (COVID-19) could be accompanied by pain complaints; mostly headache, throat ache, muscle ache, joint pain, chest pain and abdominal pain are most prevalent (Weng, 2021). After the acute stage of a COVID-19 infection, some are at risk of developing pain beyond this period (Fiala, 2022).

The mechanisms through which COVID affects pain are still not fully known. However, in a recent study from the University of Oklahoma, authors have attempted to lift the veil (mask?) of COVID-19’s effect on endogenous analgesia, tested with the conditioned pain modulation (CPM) and exercise-induced hypoalgesia (EIH) paradigms. Since impairments in endogenous analgesia are often associated with chronic pain, better understanding of COVID-19’s influence on pain inhibition can give a hint on chances of future chronic pain development among COVID-19 patients.

COVID-19 pain modulation study

For this study, all the participants (n=64) recruited were unvaccinated against COVID-19 and had no active infection. Those who had tested positive in the past twelve months were either in the symptomatic COVID-19 group (n=26) or the asymptomatic COVID-19 group (n=13) by their own account of symptoms and a past positive COVID test. Twenty controls who had not been infected were also included. All were void of any chronic pain diagnoses, musculoskeletal injuries or other disorders that may affect sensory testing results. Participants were tested on three different visits; filling questionnaires regarding mood, pain attitudes and catastrophizing.

Sensory testing protocol

Participants underwent pressure pain threshold (PPT) testing using Medoc’s AlgoMed digital pressure algometer. Each test site (i.e. vastus lateralis, and ipsilateral brachioradialis muscle belly) was tested three times in alternating order.

For Conditioned Pain Modulation assessment the PPT protocol was performed three times; once during neutral temperature foot immersion, once during 2-3 °C water temperature foot immersion, and once at the end without immersion. In between a rest period was upheld.

Exercise induced hypoalgesia was tested with PPT right after and 15 minutes post submaximal force isometric exercise until exhaustion, while the baseline PPTs of the CPM test and the first visit served as comparison.

Did the groups differ?

In conditioned pain modulation there was a significant difference, specifically in the arm, between the symptomatic group and the asymptomatic group, and the symptomatic group and the control group, while no difference was found between the control group and the asymptomatic group. The symptomatic group had ineffective CPM while the asymptomatic and the control groups had effective CPM, immediately after cold water immersion.

There were no differences in baseline pressure pain sensitivity between the control, symptomatic and asymptomatic groups.

No difference was found between the groups in EIH.

Through what mechanism does COVID-19 affect pain?

The mysteries around COVID-19’s effects are continuously being explored and exposed. In recent years many strides have been made to unravel the mechanisms of this disease’s effects on the human body.

Evolving disease variants and increasing numbers of vaccinated individuals in the population, may blur the picture pertaining the effects of COVID-19. In this paper, the study cohort was recruited and tested within a relatively short time-frame in 2021, and excluded vaccinated individuals. Interestingly, even in this cohort which consisted of young participants in their early twenties who had not been admitted to intensive care units during their disease course, significant differences were found between symptomatic and asymptomatic/control participants.

This could suggest that the severity of infection/symptoms could pose a risk for long term consequences, like chronic pain. Inefficient conditioned pain modulation response has been connected to chronic pain syndromes (Lewis, 2012), as well as to poorer outcomes from interventions like surgery (Dürsteler, 2021).

The effects of COVID-19 on pain are multi-faceted and may derive from different mechanisms. Further research is warranted to elucidate whether these laboratory findings are associated with long-term health deficits.


Clauw, D. J. (2020). Considering the potential for an increase in chronic pain after the COVID-19 pandemic. Pain, 1694–1697.

Dürsteler, C. S. (2021). Conditioned pain modulation predicts persistent pain after knee replacement surgery. Pain Reports, e910.

Fallon, N. B. (2021). Adverse effects of COVID-19-related lockdown on pain, physical activity and psychological well-being in people with chronic pain. British journal of pain, 357–364.

Fiala, K. M.-E. (2022). Post-COVID Pain Syndromes. Current pain and headache reports, 379–383.

Lewis, G. N. (2012). Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. The journal of pain, 936-944.

Mun, C. J. (2021). The early impact of COVID-19 on chronic pain: a cross-sectional investigation of a large online sample of individuals with chronic pain in the United States, April to May, 2020. Pain Medicine, 470-480.

Weng, L. M. (2021). Pain Symptoms in Patients with Coronavirus Disease (COVID-19): A Literature Review. Journal of pain research, 147–159.

Medoc Ltd.