Table 1

Pain syndromes commonly associated with infectious causes115 189–191

Variable	Pain classification
	Neuropathic pain	Nociceptive pain			Nociplastic pain
		Visceral pain	Somatic pain		Nociplastic pain
		Visceral pain	Myositis and myopathy	Arthritis, arthropathy, and others	Fibromyalgia	Others
Common infectious agents	Viruses: varicella zoster virus, flaviviruses (eg, West Nile virus, dengue virus, hepatitis C), herpesviruses (eg, herpes simplex virus, Epstein-Barr virus, cytomegalovirus), HIV, human T lymphotropic virus 1 Bacteria: Borrelia burgdorferi (Lyme disease), Brucella species, Corynebacterium diphtheriae, Mycobacterium species (leprosy, tuberculosis)	Hepatitis: hepatitis viruses A-E Myocarditis: coxsackieviruses, parvovirus, SARS-CoV-2, adenovirus, HIV, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, Trypanosoma cruzi (Chagas disease) Gastritis, peptic ulcers: Helicobacter pylori Cholecystitis: Enterobacteriaceae, cytomegalovirus, Clonorchis sinensis, Ascaris lumbricoides Pelvic: Chlamydia trachomatis, Neisseria gonorrhoeae	Viruses: coxsackie B virus, Epstein-Barr virus, hepatitis B and C, HIV, human T lymphotropic virus 1, influenza A and B Bacteria: Gram positive (eg, Staphylococcus aureus, group A Streptococcus), Gram negative (eg, Escherichia coli, Proteus species, Pseudomonas species, Salmonella species), anaerobes (Bacteroides species, Clostridium species), Mycobacterium species, Brucella species, Mycoplasma pneumoniae Fungi: Candida species Parasites: Plasmodium species, Trichinella species	Arthropathy: parvovirus B19, hepatitis viruses, chikungunya virus, rubella, alphaviruses, flaviviruses, and retroviruses Low back pain: Cutibacterium acnes, coagulase negative Staphylococcus	Viruses: HIV, Epstein-Barr virus, hepatitis viruses, influenza, SARS-CoV-2 Bacteria: Borrelia burgdorferi	Irritable bowel syndrome: Salmonella, Shigella, Escherichia coli, Campylobacter jejuni Interstitial cystitis or bladder pain syndrome: controversial, but Pseudomonas aeruginosa, Klebsiella pneumoniae, and Corynebacterium infection could be more common in certain phenotypes. Myalgic encephalitis or chronic fatigue syndrome: Epstein-Barr virus, cytomegalovirus, human herpes viruses 6 or 8, parvovirus B19, enteroviruses, lentivirus, SARS-CoV-2, Mycoplasma, Borrelia species, Coxiella burnetii Chronic pelvic pain: Chlamydia trachomatis, Neisseria gonorrhoeae
Common infectious agents	Encephalitis: herpes simplex viruses and other herpesviruses, enteroviruses (eg, coxsackievirus, poliovirus), mosquito borne viruses (eg, West Nile, western equine, and eastern equine encephalitis), rabies virus, measles, mumps, rubella
Presentation	Often described as lancinating or shooting. Numbness and dysesthesias present in stocking-glove or nerve distribution (eg, mononeuropathies). Weakness can be neurological or pain induced.	Dull, aching, often poorly localized. Gastrointestinal visceral pain is often associated with a strong affective component including emotional triggers. Neurological symptoms are uncommon except with encephalitis.	Myositis often occurs with skin manifestations (eg, dermatomyositis). Most commonly affects the shoulders, hips, and thighs. Presents with diffuse, aching pain and weakness, often associated with activities and exertion.	Arthropathy: most commonly affects the shoulders, hips, and knees. Aching pain, often worse with activity and accompanied by tenderness, stiffness, oedema, and effusion. Radiographs typically reveal degenerative changes. Focal neurological symptoms are uncommon. Back pain: diffuse aching pain that might radiate in a non-dermatomal distribution into the proximal lower extremities, worse with activity and sitting. No focal neurological findings, although radiculopathy is more common in patients with disc degeneration.	Widespread pain, often concomitant with other nociplastic conditions including non-specific spinal pain. Somatic symptoms and hypersensitivities are frequently present (eg, bowel and urinary symptoms, dyspareunia, photosensitivity, phonosensitivity). Sensory deficits might be present but in a non-anatomical distribution. Paroxysms of pain are often related to psychological stressors.	Often described as cramping (irritable bowel syndrome), aching, sharp, and diffusely localized. High co-prevalence with other nociplastic conditions. Somatic symptoms and hypersensitivities are frequently present.
Treatments	Antimicrobial treatment and nutrient supplementation are not proven to reverse longlasting neuropathology, but might be effective in preventing or even reversing neuropathies in some cases with high microbial loads. Although weak evidence supports some individual treatments (eg, high concentration capsaicin and acetyl-L-carnitine for HIV neuropathy), treatments should generally be based on established neuropathic pain treatment algorithms.	Typically supportive care and appropriate treatment of underlying infection will alleviate pain symptoms. Antimicrobial agents are highly effective for H pylori, acute bacterial cholecystitis, and early in Chagas disease.	Antimicrobial treatment could be effective for acute pain, but not for chronic pain secondary to immunological mechanisms. Antidepressants and non-steroidal anti-inflammatory drugs might provide some relief. Immunosuppressant treatment can be considered on a case-to-case basis (eg, immunoglobulins).	Arthropathy: long term antimicrobial treatment might be effective for acute pain, but not chronic pain secondary to immunological mechanisms. Steroid injections are contraindicated in acute infection but might provide benefit in immune mediated arthropathy with active inflammation. Joint replacement could be indicated in immune mediated arthropathy without concomitant infection. Antidepressants and non-steroidal anti-inflammatory drugs might provide some relief; immunosuppressant treatment can be considered on a case-to-case basis. Back pain: antibiotics might be effective if characteristic, vertebral endplate signal changes are present, but must be given for a prolonged duration due to poor intradiscal penetration. Antidepressants and non-steroidal anti-inflammatory drugs can be considered if appropriate. Most interventional treatments for discogenic low back pain are characterized by high failure rates.	Mechanisms for infection-induced fibromyalgia do not support antimicrobial treatment. Reducing risk factors for widespread pain (eg, poor sleep, low activity levels, and psychological distress) could reduce incidence. Drug treatments similar to those for neuropathic pain, with supportive measures (eg, improved sleep hygiene, low impact aerobic exercise, psychotherapy) provided as needed.	Antibiotics such as rifaximin and neomycin might be effective for irritable bowel syndrome from small intestine bacterial overgrowth. Some evidence for probiotics, but sparse evidence for prebiotics. Scant evidence for antibiotics in longstanding bladder pain syndrome. Intravesical treatment might be indicated in some patients. Other treatments for nociplastic pain syndromes include supportive treatments and pharmacotherapy (eg, antidepressants).