Association between IL‐10 systemic low level and highest pain score in patients during symptomatic SARS‐CoV‐2 infection

Abstract

Background Despite the wide variety of Covid‐19 symptoms, pain and the related mechanisms underlying unsettled nociceptive status are still under‐prioritized. Understanding the complex network of Covid‐19‐related pain may result in new lines of study. It is unknown whether patient's immunological background influences pain in the acute phase of Covid‐19, including musculoskeletal pain. Thus, we evaluated the blood levels of selected molecules that are upregulated in SARS‐CoV‐2 infection and analyzed a possible correlation with pain during Covid‐19. Methods A cohort of 20 hospitalized patients with confirmed diagnoses for Covid‐19 were evaluated in the context of pain. Visual analogic scale (VAS) was applied to quantitate pain level. Blood tests were used to determine the systemic levels of cytokines (IL‐10 and IL‐1β), substance P, and leptin. The data were correlated when appropriate to determine the association between pain‐related markers and assessed pain intensity. Results Our findings show that systemic levels of IL‐10 have strong negative correlation with pain intensity on Covid‐19 patients. Additionally, we also show that leptin systemic levels were increased in Covid‐19 patients with pain, however, with moderate positive correlation between these events. IL‐1β and SP levels did not differ between Covid‐19 patients with or without pain. Men reported less pain compared to women. No differences were found between genders in the levels of the molecules evaluated in patients with pain. Conclusion IL‐10 has been described over the years as an anti‐inflammatory and analgesic cytokine. The present data support that low IL‐10 levels might contribute to Covid‐19‐associated pain.

Interleukin-10-producing monocytes contribute to sex differences in pain resolution in mice and humans

“…The analgesic role of IL-10 is well-established in preclinical studies 16,29,37,38 . Moreover, in humans, higher levels of circulating IL-10 are associated with reduced pain [39][40][41][42][43] . However, a mechanistic explanation widely applicable from animal models to humans has not yet been demonstrated.…”

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“…The post-infection follow-up of COVID-19 survivors unveiled a range of symptoms, encompassing general pain (13.40%), joint pain (28.25%), muscle pain (13.30%), headache (9.50%), and chest pain (12.12%) [ 214 ]. Pain development is mainly associated with direct action through ACE2 receptors [ 215 ], the inflammatory cytokine storm [ 216 ], and the driving effect of prostaglandins [ 217 ]. ACE2 receptors are abundant in skeletal muscle and other organs, resulting in viral harm to the muscles, and their neurophilicity can also lead to neuronal damage, resulting in pain [ 218 ].…”

Decrypting the cellular and molecular intricacies associated with COVID-19-induced chronic pain

“…This has been proven in a study where the expression of these pro-inflammatory mediators was found to be significantly upregulated in COVID-19 patients (McFarland et al 2021 ). Moreover in a recent clinical survey the high level of inflammatory cytokine IL-1β and low level of anti-inflammatory cytokine IL-10 in systemic circulation were found to be associated with high pain score in SARS-CoV-2 patients (Bussmann et al 2022 ). The proliferation of immune cells and increased production pro-inflammatory cytokines around the sensory neurons and dorsal root ganglion in response to SARS-CoV-2 invasion leads to nociceptor sensitization.…”