Laser therapy for neuropathic pain and neuroinflammatory skin disorders: A comprehensive overview

Search strategy

A systematic literature search was conducted using PubMed, Scopus, Embase, and Web of Science for English-language articles published from January 2000 to June 2025. Search terms included combinations of:

• “Laser therapy” OR “low-level laser therapy” OR “photobiomodulation”

• “Neuropathic pain” OR “postherpetic neuralgia” OR “diabetic neuropathy” OR “complex regional pain syndrome”

• “Neuroinflammatory skin disorders” OR “atopic dermatitis” OR “psoriasis” OR “neurogenic inflammation.”

Inclusion criteria

1. Clinical trials, systematic reviews, meta-analyses, and observational studies

2. Human studies involving the use of laser therapy

3. Studies assessing pain scores, inflammation markers, skin lesions, or quality of life outcomes.

Exclusion criteria

1. Animal studies, in vitro studies

2. Case reports with fewer than three patients.

3. Studies using other light-based therapies (e.g., light-emitting diode and intense pulsed light) without lasers.

Data extraction and synthesis

Relevant data were extracted: Study design, population, intervention protocol, laser type/wavelength/energy, outcomes, and side effects. Studies were synthesized qualitatively due to heterogeneity in protocols and outcomes [Table 1].

Mechanisms of action of laser therapy

Laser therapy, particularly LLLT, utilizes wavelengths between 600 and 1000 nm to penetrate tissues and modulate biological processes. It primarily acts on cytochrome c oxidase in the mitochondrial respiratory chain, increasing adenosine triphosphate synthesis, reducing oxidative stress, and promoting nerve regeneration.^[4,5] HILT, with higher power (>500 mW), is thought to reach deeper tissues, offering more profound analgesic effects.^[6]

Mechanisms include:

• Anti-inflammatory effects: Reduction of interleukin 1 (IL-1)-1β, tumor necrosis factor-α, and prostaglandin E2.^[7]

• Neuroprotective effects: Inhibition of nerve apoptosis and promotion of neurotrophic factors.^[8]

• Analgesia: Reduction of nociceptor sensitization and modulation of peripheral C-fiber conduction.^[9]

• Microcirculatory enhancement: Vasodilation and angiogenesis through nitric oxide release [Figure 1].^[10]

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Figure 1:

Mechanisms of action of laser therapy in neuroinflammatory skin. PGE₂: Prostaglandin E₂, IL: Interleukin, TNF: Tumor Necrosis Factor.

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Postherpetic neuralgia (PHN)

PHN is characterized by chronic pain after herpes zoster reactivation. Multiple randomized controlled trials (RCTs) have shown significant pain reduction with LLLT (wavelengths 780–850 nm) applied over affected dermatomes.

• A double-blind RCT by Moore et al. (2020) showed a 65% reduction in visual analog scale (VAS) scores after 10 sessions of 830 nm LLLT.^[11]

• A meta-analysis (2022) concluded LLLT was superior to placebo in reducing PHN symptoms and improving sleep.^[12]

In addition, Mukhtar et al. observed a substantial decrease in neural hypersensitivity and pain intensity following 16 sessions of 650 nm LLLT in PHN patients.^[13]

Diabetic peripheral neuropathy (DPN)

Laser therapy improves nerve conduction velocity, reduces oxidative stress, and enhances peripheral perfusion.

Laser therapy improves nerve conduction velocity, reduces oxidative stress, and enhances peripheral perfusion.

Clinical evidence supports these effects: Chatterjee et al. demonstrated significant pain reduction and improved quality of life in diabetic neuropathy patients treated with deep tissue laser therapy.^[14]

Similarly, Shashi Kumar et al. reported marked improvement in vibration perception and neuropathy symptom scores following LLLT in diabetic peripheral neuropathy.^[15]

Complex regional pain syndrome (CRPS)

CRPS features allodynia, vasomotor instability, and inflammation. HILT is increasingly used due to its deeper tissue penetration.

Kocić et al. further validated the benefits of infrared LLLT in CRPS type I, showing both clinical and thermographic improvement with decreased edema and hyperalgesia.^[16]

Atopic dermatitis (AD)

AD involves neuroimmune dysregulation and increased nerve fiber density in lesions. LLLT may normalize this neurogenic inflammation.

Complementary approaches using blue-light phototherapy have shown modest but consistent reductions in SCORAD index and serum IL-31, supporting microbiome modulation and anti-inflammatory effects.^[17]

• Adjunctive laser therapy improved pruritus and barrier function with no adverse effects.

Psoriasis

Psoriasis is increasingly recognized as a neuroinflammatory disease involving nociceptive signaling and substance P upregulation. Laser modalities such as excimer lasers and LLLT may downregulate neuropeptides.

Feldman et al. conducted a multicenter study demonstrating that the 308-nm excimer laser achieved ≥75% PASI reduction through localized T-cell apoptosis.^[18]

Subsequent trials confirmed its efficacy and safety in psoriasis management across variable dosing and device protocols.^[19-21]

Light-emitting diode (LED) phototherapy combining red and near-infrared wavelengths also showed improvement in recalcitrant psoriasis with decreased mast cell degranulation and cytokine release.^[22,23]

Safety and adverse effects

Laser therapy is generally safe with minimal side effects, such as transient erythema, warmth, or tingling. HILT may carry a slightly higher risk of burns if improperly used. Long-term safety data remain limited, particularly for repeated use in pediatric and geriatric populations.

Recent mechanistic reviews have reinforced that photobiomodulation achieves analgesic and anti-inflammatory effects primarily through attenuation of reactive oxygen species and modulation of neuroimmune signaling cascades.^[24]

Future directions

Despite promising results, challenges remain:

• Lack of consensus on treatment parameters

• Small sample sizes and variable methodologies

• Limited data on long-term remission or recurrence.

Ongoing RCTs and mechanistic studies are needed to refine protocols and determine optimal wavelength, energy density, and session frequency.