Can Lyme Disease Cause Central Sensitization?

Persistent pain, fatigue, and sensory sensitivity
Changes in central nervous system pain processing
One possible mechanism among several under investigation

Can Lyme disease cause central sensitization? Researchers have proposed that central sensitization may contribute to persistent pain, fatigue, brain fog, and sensory hypersensitivity in some patients after Lyme disease.

Central sensitization involves changes in how the central nervous system, particularly the brain and spinal cord, processes pain and sensory signals. Batheja and colleagues describe it as a process involving increased responsiveness of central neurons and changes in synaptic activity, neurotransmitters, and neuromodulators.¹

Researchers have proposed that central sensitization may contribute to persistent symptoms in a subset of patients after Lyme disease. However, it is only one of several mechanisms being investigated. Other proposed contributors include microbial persistence, persistent microbial antigens, immune dysregulation, inflammatory or autoimmune pathways, autonomic dysfunction, peripheral nerve injury, and other changes in neural networks.⁴

No single mechanism has been shown to explain every patient with persistent Lyme disease symptoms.

What causes central sensitization?

Central sensitization is believed to develop through several interacting factors, which may include:

genetic susceptibility
increased activity of neurotransmitters that facilitate pain
reduced activity of neurotransmitters that inhibit pain pathways
repeated or prolonged nociceptive input
inflammatory and neuroimmune responses
changes in central nervous system sensory processing

The balance between pain-facilitating and pain-inhibiting pathways can function somewhat like a volume control for pain and sensory processing. When that balance is disrupted, the nervous system may respond excessively to signals that would normally produce little or no discomfort.

Infections have been proposed as one possible trigger of central sensitization in susceptible individuals, potentially through inflammatory cytokines, ongoing pain signals, and neuroimmune pathways.

In relation to Lyme disease, researchers have suggested that infection-related inflammation or other biologic consequences of illness may contribute to persistent changes in pain or sensory processing in some patients.^1,4

Patients with persistent Lyme disease symptoms may experience patterns that overlap with those described in central sensitivity syndromes. This overlap does not establish that central sensitization is the primary explanation for their illness.

What are the primary symptoms of central sensitization?

The primary manifestations associated with central sensitization can include:

widespread or amplified pain
pain from normally non-painful stimuli
fatigue
brain fog or cognitive difficulties
poor or unrefreshing sleep
heightened sensitivity to sound
heightened sensitivity to light
heightened sensitivity to touch
difficulty tolerating busy or stimulating environments

The combination and severity of symptoms can vary considerably among patients.

How does central sensitization contribute to pain?

Pain does not always arise through the same mechanism.

Researchers generally distinguish several broad categories:

Nociceptive pain results from inflammation or tissue damage in peripheral tissues.
Neuropathic pain results from injury or dysfunction involving nerves.
Nociplastic or centrally amplified pain involves altered pain processing without sufficient ongoing tissue damage or peripheral nerve injury to fully explain the severity of symptoms.

Central sensitization may contribute to persistent widespread pain by amplifying how the brain and spinal cord respond to sensory signals.

Two important manifestations are allodynia and hyperalgesia.³

Allodynia is pain produced by a stimulus that would not ordinarily be painful.
Hyperalgesia is an increased pain response to a stimulus that is normally painful.

Examples of allodynia may include pain from light touch, clothing, pressure, temperature changes, or other ordinarily non-painful stimuli.

In Lyme disease, Batheja and colleagues proposed that nociceptive, neuropathic, and centrally mediated pain may all be present to different degrees in an individual patient.¹

For example, a patient might simultaneously experience inflammatory joint pain, discomfort associated with peripheral nerve dysfunction, and more diffuse symptoms involving altered central sensory processing.

Can central sensitization cause fatigue and brain fog?

Fatigue and cognitive problems are prominent complaints among some patients with persistent symptoms following Lyme disease.

Patients may describe:

brain fog
difficulty concentrating
slower information processing
word-finding difficulty
short-term memory problems
difficulty handling several tasks at once

Fatigue can have both peripheral and central contributors. Central fatigue may occur along with cognitive impairment, sleep disruption, sensory overload, or difficulty sustaining physical or mental activity.

However, cognitive complaints and fatigue have many possible causes and should not automatically be attributed to central sensitization.

Sleep disorders, pain, medication effects, depression, anxiety, autonomic dysfunction, endocrine disorders, anemia, infection, and other medical conditions may contribute to similar symptoms.

Sensory hyperarousal after Lyme disease

Sensory hyperarousal refers to an exaggerated response to sensory input. Patients may become unusually sensitive to:

sound
light
touch
smells
movement
temperature
visually complex environments

These sensitivities can be more than minor annoyances. Some patients limit work, driving, shopping, social activities, or time in busy environments because ordinary sensory stimulation becomes overwhelming or physically uncomfortable.

Batheja and colleagues reported sensory hyperarousal among patients evaluated for post-treatment Lyme syndrome, with hearing and vision among the commonly affected sensory systems.¹

In their group of 85 patients, 70% reported hypersensitivity to light and 48% reported heightened sensitivity to sound.¹

These numbers came from a selected patient population and should not be interpreted as prevalence estimates for everyone with Lyme disease.

Auditory hyperacusis can be particularly disabling. Ordinary conversation, household sounds, background music, traffic, or sudden changes in volume may become difficult to tolerate.

What is the difference between hyperacusis and misophonia?

Not every form of sound sensitivity is the same.

Hyperacusis generally refers to an unusually reduced tolerance for the loudness or intensity of sounds. Sounds that other people tolerate comfortably may seem excessively loud, unpleasant, or even painful.

Misophonia refers to an intense involuntary emotional or physiologic response to particular sounds rather than to sound volume alone. Common trigger sounds can include chewing, slurping, sniffing, throat clearing, pen clicking, or keyboard sounds.⁷

A person with misophonia may have otherwise normal hearing but experience irritation, distress, anger, disgust, or autonomic arousal when exposed to specific trigger sounds.

This distinction is important because describing every form of sound intolerance as hyperacusis can overlook differences in how the nervous system may be processing the stimulus.

Has misophonia been reported in patients with Lyme disease?

Misophonia-like symptoms have been described in a Lyme disease patient population, but the evidence is limited.

In a 2018 retrospective psychiatric chart review, Bransfield reported auditory hyperacusis among patients with Lyme disease and described some patients as having selective hyperacusis to mouth sounds.⁶

The study focused primarily on neuropsychiatric symptoms and aggression rather than specifically investigating misophonia. It involved a selected psychiatric population and cannot establish how common misophonia is among Lyme disease patients or whether Lyme disease caused the sound intolerance.

Research therefore does not establish that Lyme disease causes misophonia.

However, the observation is relevant because some patients with Lyme disease report unusually specific reactions to certain sounds rather than simply finding all sounds too loud.

New research suggests misophonia involves altered sound processing

A 2025 study by Patro and colleagues provides additional insight into what may be happening in the nervous system of people with misophonia.⁷

The investigators compared 17 individuals with misophonia with 16 control participants. They measured electrical brain responses to standard and unexpected sounds and also evaluated hearing thresholds, speech perception in noisy environments, and selective attention.

The misophonia group had significantly reduced N1 and N2 event-related potential responses to unexpected sounds. These electrical responses are associated with early cortical processing of auditory changes.⁷

Importantly, the investigators did not find significant differences between the groups in routine hearing thresholds, speech perception, or performance on the cognitive attention task.

This suggests that misophonia may involve differences in how certain auditory information is processed by the brain rather than a conventional hearing deficit.

The study does not tell us whether the same neurophysiological pattern occurs in patients with Lyme disease who report sound intolerance. It also involved only 33 participants, primarily young adults, and did not specifically screen participants for tinnitus or hyperacusis.⁷

Nevertheless, the findings reinforce an important clinical point: a patient’s severe reaction to certain sounds can occur even when routine hearing appears normal.

Does sound sensitivity prove central sensitization?

No.

Sound sensitivity can occur in several different clinical settings and does not establish a diagnosis of central sensitization.

Potential contributors may include:

hyperacusis
misophonia
migraine
tinnitus
autonomic hyperarousal
post-concussion syndromes
anxiety or heightened threat processing
other neurologic or auditory disorders

A symptom may also involve more than one mechanism.

For example, someone could experience central sensory amplification while also having migraine, autonomic dysfunction, neuropathy, or another condition affecting sensory processing.

The presence of sound sensitivity should therefore prompt questions about the pattern and triggers rather than automatically assigning a single mechanism.

Does central sensitization explain persistent Lyme disease symptoms?

Central sensitization may help explain persistent pain, fatigue, sensory hypersensitivity, and related symptoms in some patients. It should not be used as a universal explanation for persistent illness following Lyme disease.

Rebman and Aucott described several proposed mechanisms for persistent symptoms after Lyme disease, including microbial persistence, host immune dysregulation through inflammatory or autoimmune pathways, and altered neural networks such as central sensitization.⁴

The authors emphasized that post-treatment Lyme disease is a mechanistically neutral research definition. It identifies a patient population but does not establish that every patient has the same underlying disease process.⁴

Central sensitization can also coexist with other problems.

A patient may simultaneously have:

peripheral neuropathy
small fiber neuropathy
inflammatory pain
autonomic dysfunction
sleep disturbance
medication effects
another tick-borne infection
another unrelated medical condition

For this reason, identifying symptoms consistent with central sensitization should not bring the diagnostic evaluation to an end.

How is central sensitization evaluated?

There is no single laboratory test that confirms central sensitization in a patient with persistent Lyme disease symptoms.

The evaluation is based on the symptom pattern, clinical history, physical examination, and consideration of other possible explanations.

Depending on the presentation, evaluation may include consideration of:

inflammatory or swollen joints
peripheral neuropathy or small fiber neuropathy
autonomic dysfunction or orthostatic intolerance
sleep disorders
migraine
auditory disorders when sound sensitivity is prominent
medication adverse effects
endocrine, metabolic, rheumatologic, or neurologic illness
coinfections or unrelated infections when clinically indicated

The presence of allodynia, hyperalgesia, widespread pain, fatigue, poor sleep, cognitive symptoms, or sensory hyperarousal may support consideration of central sensitization, but these findings are not specific to Lyme disease.

Can central sensitization be treated?

Treatment generally focuses on the individual patient’s symptoms, functional limitations, and contributing conditions.

Approaches used for central sensitization disorders may include carefully paced physical activity, physical therapy, improved sleep, management of autonomic symptoms, psychological support when useful, and selected medications that influence central pain processing.

Treatment should be individualized.

Some patients cannot initially tolerate aggressive exercise or rapid increases in activity, particularly when post-exertional worsening or autonomic dysfunction is present.

Recognizing central sensitization does not require dismissing symptoms as psychological. Central sensitization describes altered nervous system processing, although emotional stress, sleep, inflammation, behavior, and physical illness can all influence symptom severity.

Frequently Asked Questions

What is central sensitization?

Central sensitization refers to increased responsiveness of the brain and spinal cord to pain or sensory input. It may contribute to exaggerated pain, pain from normally non-painful stimuli, fatigue, poor sleep, cognitive difficulties, or heightened sensitivity to light, sound, and touch.

Can Lyme disease trigger central sensitization?

Researchers have proposed that infection-related inflammation and prolonged pain signaling may contribute to central sensitization in susceptible patients. Central sensitization may be one mechanism contributing to persistent Lyme disease symptoms, but the relationship has not been fully established.

Can Lyme disease cause misophonia?

Research has not established that Lyme disease causes misophonia. Misophonia-like selective sound intolerance has been reported in a Lyme disease psychiatric cohort, but this observation cannot determine causation or prevalence. Independent research suggests that misophonia itself can involve differences in cortical processing of certain sounds.

Is misophonia the same as hyperacusis?

No. Hyperacusis generally involves reduced tolerance for sound intensity or loudness. Misophonia involves an unusually strong emotional or physiologic reaction to specific trigger sounds, even when those sounds are not particularly loud.

Can someone with misophonia have normal hearing?

Yes. In a 2025 study, people with misophonia had altered electrical brain responses to unexpected sounds but did not differ significantly from controls in ordinary hearing thresholds. This suggests that misophonia is not simply the result of hearing loss.

Does central sensitization mean the symptoms are psychological?

No. Central sensitization refers to altered nervous system processing of pain and sensory signals. Psychological and emotional factors can influence symptoms, as they can in many medical conditions, but central sensitization does not mean symptoms are imagined.

Does central sensitization rule out persistent infection?

No. Identifying central sensitization does not determine whether persistent infection, microbial antigens, immune dysregulation, autonomic dysfunction, peripheral nerve injury, or another mechanism is also present. Several mechanisms remain under investigation.

Is central sensitization permanent?

Not necessarily. Symptoms may improve when contributing problems such as pain, poor sleep, autonomic dysfunction, inflammation, medication effects, or physical deconditioning are identified and addressed. Recovery patterns differ between patients.

Clinical Takeaway

Central sensitization offers one possible framework for understanding persistent pain, fatigue, cognitive difficulties, allodynia, and sensory hyperarousal following Lyme disease.

Sound sensitivity deserves particular attention because it can take different forms. Some patients experience general hyperacusis, while others describe strong reactions to specific sounds resembling misophonia.

Research does not establish that Lyme disease causes misophonia. However, selective sound intolerance has been reported in Lyme patients, and newer research suggests that misophonia can involve measurable differences in cortical auditory processing even when ordinary hearing remains normal.

Central sensitization should not be assumed to explain every symptom or every patient. A complete evaluation should consider inflammatory, neuropathic, infectious, immune, autonomic, auditory, metabolic, medication-related, and other potential contributors.

Current evidence supports a multifactorial model in which central sensitization may contribute alongside immune, neurologic, autonomic, and other biologic mechanisms.

Editor’s note: Many of my patients appear to experience symptoms consistent with central sensitization. For transparency, I am an author of the International Lyme and Associated Diseases Society guidelines, which do not dismiss the persistent infection hypothesis.

References

Batheja S, Nields JA, Landa A, Fallon BA. Post-treatment Lyme syndrome and central sensitization. J Neuropsychiatry Clin Neurosci. 2013;25(3):176-186. doi:10.1176/appi.neuropsych.12090223. PubMed
Yunus MB. Fibromyalgia and overlapping disorders: The unifying concept of central sensitivity syndromes. Semin Arthritis Rheum. 2007;36(6):339-356. doi:10.1016/j.semarthrit.2006.12.009. PubMed
Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: Clinical manifestations and mechanisms. Lancet Neurol. 2014;13(9):924-935. doi:10.1016/S1474-4422(14)70102-4. PubMed
Rebman AW, Aucott JN. Post-treatment Lyme disease as a model for persistent symptoms in Lyme disease. Front Med (Lausanne). 2020;7:57. doi:10.3389/fmed.2020.00057. PubMed
Talbot NC, Spillers NJ, Luther P, et al. Lyme disease and post-treatment Lyme disease syndrome: Current and developing treatment options. Cureus. 2023;15(8):e43112. doi:10.7759/cureus.43112. PubMed
Bransfield RC. Aggressiveness, violence, homicidality, homicide, and Lyme disease. Neuropsychiatr Dis Treat. 2018;14:693-713. doi:10.2147/NDT.S155143. PubMed
Patro C, Wasko E, Prabhu P, Srinivasan NK. Investigating neurophysiological, perceptual, and cognitive mechanisms in misophonia. Biology (Basel). 2025;14(3):238. doi:10.3390/biology14030238. PubMed

Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention

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