Pain Caused by Infection and Related Management Strategies—A High-Score Review

Infection has always been the main cause of the burden of human morbidity and mortality, and pain is one of the early warning signs of

Varicella zoster virus (VZV)

VZV infection causes chickenpox and shingles

Human Immunodeficiency Virus (HIV)

The development of antiretroviral therapy has improved prognosis in HIV-infected patients, but it rarely completely destroys the virus, and more than 50% of people living with HIV develop chronic non-cancerous pain

HIV infection carries a greater risk of nociceptive pain, usually with abdominal pain, chest pain, musculoskeletal pain, and headache, and a higher

Herpes simplex virus (HSV)

Most people are infected with herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2) through mucosal surface or abrasive skin-to-skin contact, and acute symptoms may occur after infection, but most are asymptomatic

Hepatitis C virus (HCV)

Common extrahepatic manifestations of HCV include arthralgia, lymphoma, diabetes, and chronic kidney disease, most of which are associated

Novel coronavirus (SARS-CoV-2)

20% to 60% of SARS-CoV-2 admissions are associated with acute pain, with common complaints of myalgia or arthralgia, headache and sore throat (≥25%); This is followed by chest pain, spinal pain, abdominal pain, and other neurological symptoms that are not headaches
.

Symptoms can be caused by a variety of factors, including immune response, fever, and viral invasion (arthralgia, myositis, myocarditis, or chest pain
).

About 5-15% of hospitalized patients with COVID-19 experience abdominal pain, which may be related
to gastrointestinal angiotensin-converting enzyme 2 receptor binding to the virus, lymph node abnormalities, lung pain, or visceral dilation.

One observational study found that acute pain reduced death and intensive care rates, which may be associated
with activation of neurotransmitters involved in pain regulation and distraction.

Borrelia burgdorferi (Lyme disease)

Pain in patients with the disease can occur immediately after Borrelia burgdorferi infection (stage 1 includes local pain and systemic symptoms), days to weeks after infection (stage 2 includes severe headache, myalgia, and arthralgia), and stage 3, which can occur months to years after infection, and is thought to be secondary to central sensitization
.

Lyme disease syndrome occurs after treatment in 10% to 20% of patients, which refers to persistent fatigue, musculoskeletal pain, and cognitive dysfunction similar to fibromyalgia after antibiotic treatment, also known as chronic Lyme disease
.

More than 75% of patients present with headache, arthralgia, myalgia, and neuropathic pain
.

At the same time, cognitive deficits, fatigue, and sleep dysfunction affect most people with
Lyme disease.

Mycobacterium leprosy (leprosy)

Leprosy is a chronic infectious disease caused by Mycobacterium leprosy and is divided into oligobacterial and polysmozoic types
.

Although sensory loss, visual disturbances, and disfigurement are more common, neuropathic pain
is present in about 35% of patients.

The bacterium can enter the nervous system through endothelial cells or infected monocytes, showing affinity
for Schwann cells.

The type of neuropathic pain varies depending on the burden of disease, with oligobacterial leprosy usually affecting the ulnar and fibular nerves, while advanced disease often results in diffuse symmetrical polyneuropathy, often involving the facial and trigeminal nerves
.

In addition to neuropathic pain, leprosy patients also have nociceptive pain
from tissue invasion injuries (eg, skin, nose, testicles) and disfigurement.

Treponemal syphilis

Treponema pallidum is the causative agent of syphilis, often transmitted through bloodstream and sexual contact
.

Patients generally develop chancre (characteristic sign of primary syphilis) within three weeks of infection, and stage two syphilis features such as syphilis rash and other manifestations of pain and discomfort within three months, including lymph node abnormalities, mucosal lesions, gastritis, hepatitis, glomerulonephritis, and lung abscess
.

The incubation period is usually less than one year, with the appearance of tertiary syphilis, the most common of which are neurologic manifestations (eg, paresthesia, ataxia, visual impairment, and cognitive impairment), followed by cardiovascular complications (eg, aortic aneurysm and myocarditis) and syphilitic gumoidia
.

Penicillin is the treatment of choice at any stage, but even if the bacteria are eliminated, the pain may persist when the organ damage is severe
.

In addition, antibiotics and antiviral therapy for infectious diseases may also be associated with chronic pain, often dose- or time-dependent, particularly in relation to the use of antibiotics and peripheral neuropathy (Table 1
).

Table 1 Antibiotics for the treatment of associated peripheral neuropathy and other pain

Infection can cause pain through a variety of mechanisms, with pain being the core symptom of acute infection and can be caused
directly by physical (eg, septic arthritis) or visceral (eg, appendicitis) tissue invasion, or by nerve damage (eg, acute herpes zoster neuritis) and concomitant inflammatory processes.

After the infection resolves in some patients, the immune response caused by it persists and causes chronic pain
.

At present, postinfectious chronic pain is not fully recognized, but can take many forms such as nociceptive pain, neuropathic pain and injury plasticity pain (injury plasticity pain is a semantic term proposed by the international pain research community to describe the third type of pain, which is different from nociceptive pain and neuropathic pain, but the specific pain mechanism has not been clarified).


Most treatments for post-infection chronic pain are empirical, and in the absence of evidence of persistent infection, antibiotics provide little
benefit.

Similar to preventing acute pain from other causes from turning into chronic pain, early treatment through a biopsychosocial framework can prevent post-infection chronic pain syndrome, but more research
is needed.

References:

1.
Cohen SP, Wang EJ, Doshi TL，et al.
Chronic pain and infection: mechanisms,causes,conditions,treatments,and controversies.
BMJ Medicine 2022; 1:e000108.

2.
Expert group on the preparation of consensus on the diagnosis and treatment of post-shingle neuralgia.
Chinese expert consensus on the diagnosis and treatment of post-shingles neuralgia[J].
Chinese Journal of Pain Medicine,2016,22(03):161-167.

3.
Wei Wei.
Clinical features and treatment points of Lyme disease[J].
Chinese Journal of Industrial Medicine,2022,35(04):340-342.

4.
Fitzcharles MA, Cohen SP, Clauw DJ, Littlejohn G, Usui C, Häuser W.
Nociplastic pain: towards an understanding of prevalent pain conditions.
Lancet.
2021 May 29; 397(10289):2098-2110.